COVID-19 Updates

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

A new study urges people to continue wearing protective masks in medical settings, even though the U.S. public health emergency declaration around COVID-19 has expired.

Masks continue to lower the risk of catching the virus during medical visits, according to the study, published in Annals of Internal Medicine. And there was not much difference between wearing surgical masks and N95 respirators in health care settings.

The researchers reviewed 3 randomized trials and 21 observational studies to compare the effectiveness of those and cloth masks in reducing COVID-19 transmission.

“Masking in interactions between patients and health care personnel should continue to receive serious consideration as a patient safety measure,” Tara N. Palmore, MD, of George Washington University, Washington, and David K. Henderson, MD, of the National Institutes of Health, Bethesda, Md., wrote in an opinion article accompanying the study.

“In our enthusiasm to return to the appearance and feeling of normalcy, and as institutions decide which mitigation strategies to discontinue, we strongly advocate not discarding this important lesson learned for the sake of our patients’ safety,” Dr. Palmore and Dr. Henderson wrote.

Surgical masks limit the spread of aerosols and droplets from people who have the flu, coronaviruses or other respiratory viruses, CNN reported. And while masks are not 100% effective, they substantially lower the amount of virus put into the air via coughing and talking.

The study said one reason people should wear masks to medical settings is because “health care personnel are notorious for coming to work while ill.” Transmission from patient to staff and staff to patient is still possible, but rare, when both are masked.

The review authors reported no conflicts of interest. Dr. Palmore has received grants from the NIH, Rigel, Gilead, and AbbVie, and Dr. Henderson is a past president of the Society for Healthcare Epidemiology of America.

A version of this article first appeared on WebMD.com.

Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren. 

Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.

Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.

“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.” 

Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Debbie’s death was a painful reminder to Traci and her family that COVID hasn’t actually gone anywhere. Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.

The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members. 

It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.

“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”

The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.

“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
 

Historic drop in life expectancy

More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.

What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.

“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”

By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century. 

Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.

As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
 

What is an acceptable threshold of death?

In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID. 

The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.

“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said. 

Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J.,  home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.

“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”

At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.

“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.” 

One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”

Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.

What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks. 

“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”

Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.

“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”

A version of this article first appeared on WebMD.com.

Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren. 

Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.

Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.

“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.” 

Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Debbie’s death was a painful reminder to Traci and her family that COVID hasn’t actually gone anywhere. Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.

The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members. 

It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.

“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”

The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.

“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
 

Historic drop in life expectancy

More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.

What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.

“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”

By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century. 

Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.

As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
 

What is an acceptable threshold of death?

In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID. 

The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.

“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said. 

Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J.,  home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.

“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”

At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.

“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.” 

One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”

Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.

What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks. 

“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”

Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.

“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”

A version of this article first appeared on WebMD.com.

Traci Sikes’s older sister Debbie had survived several health setbacks in life – a heart attack, a cancer diagnosis, and a couple of botched surgeries for a bad back. But by early 2023, the 68-year-old from Brownwood, Tex., was in remission from lymphoma, feeling stronger, and celebrating a birthday for one of her 11 beloved grandchildren. 

Then Debbie caught COVID-19. Less than 2 months later, in March, she died of severe lung damage caused by the coronavirus.

Traci was able to make the trip from her home in Washington state to Texas to be with Debbie before she died. She was grateful that she arrived while her sister was still lucid and to hear her sister’s last word – “love” – spoken to one of her grandchildren before she took her final breath.

“My sister was wonderful,” Sikes said. “And she shouldn’t be gone.” 

Just 6 months after President Joe Biden declared last fall that “the pandemic is over,” Debbie’s death was a painful reminder to Traci and her family that COVID hasn’t actually gone anywhere. Just as both the World Health Organization and U.S. government recently ended the 3-year-old coronavirus public health emergency, COVID is still killing more than 100 people every day in the U.S., according to the CDC, and amid widespread efforts to move on and drop protective measures, the country’s most vulnerable people are still at significant risk.

The prevailing attitude that we need to learn to live with the current level of risk feels like a “slap in the face,” for COVID grievers who have already paid the price,” said Sabila Khan, who cofounded a Facebook group for COVID loss support, which now has more than 14,000 members. 

It also minimizes the continuing loss of life and that so many people are still dying traumatic and unnecessary deaths, she said.

“It feels like it’s been brushed aside,” she said. “Like, ‘It’s business as usual. It’s over. Take off your mask.’ My family and I are still masked, and we’re probably the only ones masked in any given room.”

The abandoning of protective measures also fails to recognize the ongoing and catastrophic risks of long COVID and the experiences of an estimated 26 million people in the U.S. living with long COVID.

“It’s been drummed into us that death is the only serious outcome [of the virus] and we still haven’t made enough space for the idea that long COVID is a very serious outcome,” said David Putrino, PhD, director of rehabilitation innovation for the Mount Sinai Health System in New York, who has helped care for thousands of patients with long COVID.
 

Historic drop in life expectancy

More than 1.1 million Americans have died from COVID over the past 3 years, and experts say the official numbers are likely underestimated because of errors in death certificate reporting. Although deaths have waned from earlier in the pandemic, the disease has become the fourth leading cause of death in the United States after heart disease, cancer, and “unintentional injury” such as drug overdoses.

What makes these deaths all the more tragic is that COVID is a preventable disease, said Carla Sevin, MD, a critical care doctor and director of the Pulmonary Patient Care Center at Vanderbilt University Medical Center in Nashville, Tenn. Masking, available vaccines, and social distancing have all been shown to significantly lower the risk of spreading and catching the virus. New drugs have also made it possible for infected people to survive COVID.

“It’s possible to not spread COVID,” she said. “It’s possible to protect yourself against COVID. It’s possible to treat COVID. And we’re doing all of those things imperfectly.”

By the end of 2021, Americans overall were dying 3 years sooner, on average, than they were before the pandemic, with life expectancy dropping from 79 years to 76 years, the largest decline in a century. 

Globally, the COVID death toll is nearing 7 million. Across all ages, on average, each person who died passed away 10 years younger than they otherwise would have. That’s tens of millions of years wiped away.

As U.S. surgeon and health researcher Atul Gawande, MD, put it in a New York Times essay about the pandemic response: “Human development has been pushed into reverse.”
 

What is an acceptable threshold of death?

In the United States, more than 80% of deaths from the disease have been in people age 65 and older. Underlying medical conditions and disabilities also raise the risk of severe illness and dying from COVID. 

The virus is also disproportionately killing Black, Hispanic, and Indigenous people and those with less access to health care. Racialized groups are dying from COVID at younger ages. COVID advocates and Americans who’ve lost loved ones to the disease say our willingness to accept these facts and the current mortality rate amounts to health-based discrimination.

“Would politicians be approaching this differently had it mostly affected rich white people?” Ms. Khan said. 

Ms. Khan’s dad, Shafqat, was an advocate and community organizer for Pakistani immigrants. After contracting COVID, he was rushed to a hospital near his daughter’s Jersey City, N.J.,  home from a rehab facility where he was being treated for an aggressive form of Parkinson’s disease. For the 8 days her father was in the hospital, she and other family members couldn’t visit him, and he wasn’t even well enough to talk on the phone. He died from COVID in April 2020.

“My father was an extraordinary person who did so much good and he died alone, terrified in a hospital,” she said. “I can’t even wrap my head around that and how he deserved more. No one deserves that.”

At Vanderbilt University Medical Center, where she works as a critical care doctor, COVID deaths are now different from those in the early days of the pandemic, Dr. Sevin said. Most patients now in the intensive care unit are older and immunocompromised – and they tend to blend in more with others in the intensive care unit. That makes the impact of COVID even more hidden and easily ignored.

“It’s easy not to value somebody who’s an invisible number you don’t know,” she said. “You don’t see them writing their will and talking to their best friend. You don’t see the tears rolling down their face because they know what’s going to happen to them and they’re going to asphyxiate to death.” 

One COVID patient who died recently in Dr. Sevin’s ICU ward was an older woman who had no living relatives. “She was very, very lonely, and we would always stand outside the door on rounds, and she would motion for us to come in, but we had to then all gown up,” Dr. Sevin said. “It just breaks your heart that people are still having to go through it.”

Dr. Sevin finds it frustrating that so many of the measures that public health officials fought so hard for over the last 3 years – including masking guidelines, government-funded vaccine clinics, and access to potentially life-saving antiviral medications – are now going away because of the lifting of the pandemic emergency declaration.

What makes matters worse, she said, is that public consciousness about taking precautions to protect others is starting to disappear in favor of an “all or nothing attitude” about the continued risks. 

“Like either I’m going to stay home and be a hermit, or I’m going to just throw caution to the wind and go to bars and let people yell in my face,” she said. “We learned some hard lessons, and I wish we could hold onto those.”

Americans like Traci Sikes who’ve lost loved ones and health care workers on the front lines say it is particularly frustrating that so many people are framing the current response to the risks of COVID as “personal choice” over responsibility to others, as well as a sense of fatalism and lack of urgent care.

“Why does nobody seem to be angry about this?” Ms. Sikes said. “People talk about COVID like it’s just another thing to die from. But my sister didn’t have to die from it at all.”

A version of this article first appeared on WebMD.com.

When the federal government’s public health emergency (PHE) ended on May 11, the Centers for Disease Control and Prevention scaled back the amount of COVID-related data that it had required hospitals to collect and report during the previous 3 years. The CDC had to do this, an agency spokesman said in an interview, because “CDC’s authorizations to collect certain types of public health data” expired with the PHE.

The question that arises from this policy change is whether the CDC will now have sufficient information on the evolution and spread of COVID to inform public health decisions in a timely manner. The CDC insists that it will have enough data to keep up with the virus, which repeatedly defied scientists’ expectations during the course of the pandemic. But some experts have doubts about whether this will turn out to be the case.

While the COVID pandemic is subsiding and transitioning to an endemic phase, many things about the coronavirus are still not understood, noted Marisa Eisenberg, PhD, associate professor of epidemiology at the University of Michigan, Ann Arbor.

“COVID is here to stay, and it ebbs and flows but is staying at fairly consistent levels across the country,” she said in an interview. “Meanwhile, we haven’t established a regular seasonality for COVID that we see for most other respiratory illnesses. We’re still seeing pretty rapidly invading new waves of variants. With flu and other respiratory illnesses, you often see a particular variant in each season. There’s an established pattern. For COVID, that’s still shifting.”

Similarly, Sam Scarpino, PhD, a public health expert at Northeastern University, Boston, told the New York Times: “The CDC is shuffling COVID into the deck of infectious diseases that we’re satisfied living with. One thousand deaths a week is just unacceptable.”

William Schaffner, MD, a professor of preventive medicine and health policy at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview that “how we deal with influenza is something of a template or a model for what the CDC is trying to get to with COVID.” It’s not practical for physicians and hospitals to report every flu case, and the same is now true for COVID. However, “we’re still asking for data on people who are hospitalized with COVID to be reported. That will give us a measure of the major public health impact.”

Dr. Eisenberg doesn’t fully subscribe to this notion. “COVID and influenza are both respiratory illnesses, and our initial pandemic response was based on playbooks that we’d built for potential flu pandemics. But COVID is not the flu. We still have to grapple with the fact that it’s killing a lot more people than the flu does. So maybe it’s a template, but not a perfect one.”
 

What data is being deleted

The CDC is now requiring hospitals to submit COVID-related data weekly, rather than daily, as it previously had. In addition, the agency has cut the number of data elements that hospitals must report from 62 to 44. Among the data fields that are now optional for hospitals to report are the numbers of hospitalized children with suspected or lab-confirmed COVID; hospitalized and ventilated COVID patients; adults in the ICU with suspected or lab-confirmed COVID; adult and pediatric admissions with suspected COVID; COVID-related emergency department visits; and inpatients with hospital-acquired COVID.

Although widely feared by health care workers and the public, hospital-acquired COVID has never been a major factor in the pandemic, Dr. Schaffner said. “So why ask for something that’s actually not so critical? Let’s keep the emphasis on rapid, accurate reporting of people who are hospitalized because of this disease.”

Akin Demehin, senior director for quality and patient safety policy for the American Hospital Association, agreed that the rate of hospital-acquired COVID cases “has been very low throughout the pandemic.” That was one reason why CDC made this measure optional.

Dr. Eisenberg concurred with this view. “We worried about [hospital-acquired COVID] a lot, and then, because people were very careful, it wasn’t as much of a problem as we feared it would be.” But she added a note of caution: “Masking and other [preventive guidelines] are shifting in hospitals, so it will be interesting to see whether that affects things.”
 

CDC justifies its new policy

To put the hospital data reporting changes in context, it’s important to know that CDC will no longer directly track community levels of COVID and the percentage of tests that come back positive for COVID, which until now were used to measure transmission rates. (Laboratories no longer have to report these test data, whether they are in hospitals or in the community.) To track death rates, CDC will rely on the National Vital Statistics System, which is accurate but lags other kinds of surveillance by 2-3 weeks, according to the New York Times.

In a recent MMWR report, CDC defended its new COVID surveillance system, saying: “Weekly COVID-19 hospital admission levels and the percentage of all COVID-19–associated deaths will be primary surveillance indicators. Emergency department visits and percentage of positive SARS-CoV-2 laboratory test results will help detect early changes in trends. Genomic surveillance will continue to help identify and monitor SARS-CoV-2 variants.”

Clarifying the latter point, CDC said that national genomic surveillance, along with wastewater surveillance, will continue to be used to estimate COVID variant proportions. Dr. Eisenberg stressed the importance of genomic surveillance at the hundreds of sites that CDC now maintains across the country. But currently, many of these sites are only monitoring the level of COVID.

CDC also observed that COVID-19 hospital admission levels have been shown to be “concordant” with community levels of SARS-CoV-2 infection. Therefore, rates of COVID-associated admissions and the percentages of positive test results, COVID ED visits, and COVID deaths are “suitable and timely indicators of trends in COVID-19 activity and severity.”
 

Ready to shift to voluntary reporting?

In a news release, AHA praised the “streamlining” of CDC requirements for data reporting but said that it hoped that mandatory reporting would be phased out as soon as possible.

The association noted that this would require action by the Centers for Medicare & Medicaid Services. CMS now enforces the CDC requirements with a “condition of participation” (COP) provision, by which noncompliant hospitals could be excluded from Medicare. CMS has extended this COP to April 30, 2024, although it could choose to ask the Secretary of Health and Human Services to terminate it earlier.

If mandatory reporting were repealed, would most hospitals still report on the key COVID metrics? Mr. Demehin noted that before CMS implemented its COP, hospitals reported COVID data voluntarily, “and the participation rate was well over 90%. So setting up a mechanism similar to that is something we’ve encouraged CMS to consider.”

Dr. Eisenberg is skeptical. While bigger hospitals with more resources might continue reporting voluntarily, she said, safety-net hospitals in underserved areas might not, because they are especially short staffed. “Then you have disparities in which hospitals will report.”
 

Vaccinations: The sleeping dragon

COVID continues to ravage the nation. According to CDC statistics, there were 1,109 deaths from COVID in the U.S. in the week ending May 6, and total deaths have hit 1.13 million. There were 1,333 new COVID-related hospital admissions, and 7,261 people were in the hospital because of COVID.

Another eye-catching number: Only 16.9% of the U.S. population has received an updated COVID vaccine booster. Dr. Schaffner thinks that this is what we should really keep our eye on. While the combination of vaccinations and widespread SARS-CoV-2 infections has conferred herd immunity on most Americans, he said it’s temporary. “Whether your immunity comes from the virus and recovery from disease or from the vaccines, that immunity will wane over time. Unless we keep our vaccination rate up, we may see more future cases. We’ll have to see how that works out. But I’m nervous about that, because people do appear to be nonchalant.”

A version of this article first appeared on Medscape.com.

When the federal government’s public health emergency (PHE) ended on May 11, the Centers for Disease Control and Prevention scaled back the amount of COVID-related data that it had required hospitals to collect and report during the previous 3 years. The CDC had to do this, an agency spokesman said in an interview, because “CDC’s authorizations to collect certain types of public health data” expired with the PHE.

The question that arises from this policy change is whether the CDC will now have sufficient information on the evolution and spread of COVID to inform public health decisions in a timely manner. The CDC insists that it will have enough data to keep up with the virus, which repeatedly defied scientists’ expectations during the course of the pandemic. But some experts have doubts about whether this will turn out to be the case.

While the COVID pandemic is subsiding and transitioning to an endemic phase, many things about the coronavirus are still not understood, noted Marisa Eisenberg, PhD, associate professor of epidemiology at the University of Michigan, Ann Arbor.

“COVID is here to stay, and it ebbs and flows but is staying at fairly consistent levels across the country,” she said in an interview. “Meanwhile, we haven’t established a regular seasonality for COVID that we see for most other respiratory illnesses. We’re still seeing pretty rapidly invading new waves of variants. With flu and other respiratory illnesses, you often see a particular variant in each season. There’s an established pattern. For COVID, that’s still shifting.”

Similarly, Sam Scarpino, PhD, a public health expert at Northeastern University, Boston, told the New York Times: “The CDC is shuffling COVID into the deck of infectious diseases that we’re satisfied living with. One thousand deaths a week is just unacceptable.”

William Schaffner, MD, a professor of preventive medicine and health policy at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview that “how we deal with influenza is something of a template or a model for what the CDC is trying to get to with COVID.” It’s not practical for physicians and hospitals to report every flu case, and the same is now true for COVID. However, “we’re still asking for data on people who are hospitalized with COVID to be reported. That will give us a measure of the major public health impact.”

Dr. Eisenberg doesn’t fully subscribe to this notion. “COVID and influenza are both respiratory illnesses, and our initial pandemic response was based on playbooks that we’d built for potential flu pandemics. But COVID is not the flu. We still have to grapple with the fact that it’s killing a lot more people than the flu does. So maybe it’s a template, but not a perfect one.”
 

What data is being deleted

The CDC is now requiring hospitals to submit COVID-related data weekly, rather than daily, as it previously had. In addition, the agency has cut the number of data elements that hospitals must report from 62 to 44. Among the data fields that are now optional for hospitals to report are the numbers of hospitalized children with suspected or lab-confirmed COVID; hospitalized and ventilated COVID patients; adults in the ICU with suspected or lab-confirmed COVID; adult and pediatric admissions with suspected COVID; COVID-related emergency department visits; and inpatients with hospital-acquired COVID.

Although widely feared by health care workers and the public, hospital-acquired COVID has never been a major factor in the pandemic, Dr. Schaffner said. “So why ask for something that’s actually not so critical? Let’s keep the emphasis on rapid, accurate reporting of people who are hospitalized because of this disease.”

Akin Demehin, senior director for quality and patient safety policy for the American Hospital Association, agreed that the rate of hospital-acquired COVID cases “has been very low throughout the pandemic.” That was one reason why CDC made this measure optional.

Dr. Eisenberg concurred with this view. “We worried about [hospital-acquired COVID] a lot, and then, because people were very careful, it wasn’t as much of a problem as we feared it would be.” But she added a note of caution: “Masking and other [preventive guidelines] are shifting in hospitals, so it will be interesting to see whether that affects things.”
 

CDC justifies its new policy

To put the hospital data reporting changes in context, it’s important to know that CDC will no longer directly track community levels of COVID and the percentage of tests that come back positive for COVID, which until now were used to measure transmission rates. (Laboratories no longer have to report these test data, whether they are in hospitals or in the community.) To track death rates, CDC will rely on the National Vital Statistics System, which is accurate but lags other kinds of surveillance by 2-3 weeks, according to the New York Times.

In a recent MMWR report, CDC defended its new COVID surveillance system, saying: “Weekly COVID-19 hospital admission levels and the percentage of all COVID-19–associated deaths will be primary surveillance indicators. Emergency department visits and percentage of positive SARS-CoV-2 laboratory test results will help detect early changes in trends. Genomic surveillance will continue to help identify and monitor SARS-CoV-2 variants.”

Clarifying the latter point, CDC said that national genomic surveillance, along with wastewater surveillance, will continue to be used to estimate COVID variant proportions. Dr. Eisenberg stressed the importance of genomic surveillance at the hundreds of sites that CDC now maintains across the country. But currently, many of these sites are only monitoring the level of COVID.

CDC also observed that COVID-19 hospital admission levels have been shown to be “concordant” with community levels of SARS-CoV-2 infection. Therefore, rates of COVID-associated admissions and the percentages of positive test results, COVID ED visits, and COVID deaths are “suitable and timely indicators of trends in COVID-19 activity and severity.”
 

Ready to shift to voluntary reporting?

In a news release, AHA praised the “streamlining” of CDC requirements for data reporting but said that it hoped that mandatory reporting would be phased out as soon as possible.

The association noted that this would require action by the Centers for Medicare & Medicaid Services. CMS now enforces the CDC requirements with a “condition of participation” (COP) provision, by which noncompliant hospitals could be excluded from Medicare. CMS has extended this COP to April 30, 2024, although it could choose to ask the Secretary of Health and Human Services to terminate it earlier.

If mandatory reporting were repealed, would most hospitals still report on the key COVID metrics? Mr. Demehin noted that before CMS implemented its COP, hospitals reported COVID data voluntarily, “and the participation rate was well over 90%. So setting up a mechanism similar to that is something we’ve encouraged CMS to consider.”

Dr. Eisenberg is skeptical. While bigger hospitals with more resources might continue reporting voluntarily, she said, safety-net hospitals in underserved areas might not, because they are especially short staffed. “Then you have disparities in which hospitals will report.”
 

Vaccinations: The sleeping dragon

COVID continues to ravage the nation. According to CDC statistics, there were 1,109 deaths from COVID in the U.S. in the week ending May 6, and total deaths have hit 1.13 million. There were 1,333 new COVID-related hospital admissions, and 7,261 people were in the hospital because of COVID.

Another eye-catching number: Only 16.9% of the U.S. population has received an updated COVID vaccine booster. Dr. Schaffner thinks that this is what we should really keep our eye on. While the combination of vaccinations and widespread SARS-CoV-2 infections has conferred herd immunity on most Americans, he said it’s temporary. “Whether your immunity comes from the virus and recovery from disease or from the vaccines, that immunity will wane over time. Unless we keep our vaccination rate up, we may see more future cases. We’ll have to see how that works out. But I’m nervous about that, because people do appear to be nonchalant.”

A version of this article first appeared on Medscape.com.

When the federal government’s public health emergency (PHE) ended on May 11, the Centers for Disease Control and Prevention scaled back the amount of COVID-related data that it had required hospitals to collect and report during the previous 3 years. The CDC had to do this, an agency spokesman said in an interview, because “CDC’s authorizations to collect certain types of public health data” expired with the PHE.

The question that arises from this policy change is whether the CDC will now have sufficient information on the evolution and spread of COVID to inform public health decisions in a timely manner. The CDC insists that it will have enough data to keep up with the virus, which repeatedly defied scientists’ expectations during the course of the pandemic. But some experts have doubts about whether this will turn out to be the case.

While the COVID pandemic is subsiding and transitioning to an endemic phase, many things about the coronavirus are still not understood, noted Marisa Eisenberg, PhD, associate professor of epidemiology at the University of Michigan, Ann Arbor.

“COVID is here to stay, and it ebbs and flows but is staying at fairly consistent levels across the country,” she said in an interview. “Meanwhile, we haven’t established a regular seasonality for COVID that we see for most other respiratory illnesses. We’re still seeing pretty rapidly invading new waves of variants. With flu and other respiratory illnesses, you often see a particular variant in each season. There’s an established pattern. For COVID, that’s still shifting.”

Similarly, Sam Scarpino, PhD, a public health expert at Northeastern University, Boston, told the New York Times: “The CDC is shuffling COVID into the deck of infectious diseases that we’re satisfied living with. One thousand deaths a week is just unacceptable.”

William Schaffner, MD, a professor of preventive medicine and health policy at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview that “how we deal with influenza is something of a template or a model for what the CDC is trying to get to with COVID.” It’s not practical for physicians and hospitals to report every flu case, and the same is now true for COVID. However, “we’re still asking for data on people who are hospitalized with COVID to be reported. That will give us a measure of the major public health impact.”

Dr. Eisenberg doesn’t fully subscribe to this notion. “COVID and influenza are both respiratory illnesses, and our initial pandemic response was based on playbooks that we’d built for potential flu pandemics. But COVID is not the flu. We still have to grapple with the fact that it’s killing a lot more people than the flu does. So maybe it’s a template, but not a perfect one.”
 

What data is being deleted

The CDC is now requiring hospitals to submit COVID-related data weekly, rather than daily, as it previously had. In addition, the agency has cut the number of data elements that hospitals must report from 62 to 44. Among the data fields that are now optional for hospitals to report are the numbers of hospitalized children with suspected or lab-confirmed COVID; hospitalized and ventilated COVID patients; adults in the ICU with suspected or lab-confirmed COVID; adult and pediatric admissions with suspected COVID; COVID-related emergency department visits; and inpatients with hospital-acquired COVID.

Although widely feared by health care workers and the public, hospital-acquired COVID has never been a major factor in the pandemic, Dr. Schaffner said. “So why ask for something that’s actually not so critical? Let’s keep the emphasis on rapid, accurate reporting of people who are hospitalized because of this disease.”

Akin Demehin, senior director for quality and patient safety policy for the American Hospital Association, agreed that the rate of hospital-acquired COVID cases “has been very low throughout the pandemic.” That was one reason why CDC made this measure optional.

Dr. Eisenberg concurred with this view. “We worried about [hospital-acquired COVID] a lot, and then, because people were very careful, it wasn’t as much of a problem as we feared it would be.” But she added a note of caution: “Masking and other [preventive guidelines] are shifting in hospitals, so it will be interesting to see whether that affects things.”
 

CDC justifies its new policy

To put the hospital data reporting changes in context, it’s important to know that CDC will no longer directly track community levels of COVID and the percentage of tests that come back positive for COVID, which until now were used to measure transmission rates. (Laboratories no longer have to report these test data, whether they are in hospitals or in the community.) To track death rates, CDC will rely on the National Vital Statistics System, which is accurate but lags other kinds of surveillance by 2-3 weeks, according to the New York Times.

In a recent MMWR report, CDC defended its new COVID surveillance system, saying: “Weekly COVID-19 hospital admission levels and the percentage of all COVID-19–associated deaths will be primary surveillance indicators. Emergency department visits and percentage of positive SARS-CoV-2 laboratory test results will help detect early changes in trends. Genomic surveillance will continue to help identify and monitor SARS-CoV-2 variants.”

Clarifying the latter point, CDC said that national genomic surveillance, along with wastewater surveillance, will continue to be used to estimate COVID variant proportions. Dr. Eisenberg stressed the importance of genomic surveillance at the hundreds of sites that CDC now maintains across the country. But currently, many of these sites are only monitoring the level of COVID.

CDC also observed that COVID-19 hospital admission levels have been shown to be “concordant” with community levels of SARS-CoV-2 infection. Therefore, rates of COVID-associated admissions and the percentages of positive test results, COVID ED visits, and COVID deaths are “suitable and timely indicators of trends in COVID-19 activity and severity.”
 

Ready to shift to voluntary reporting?

In a news release, AHA praised the “streamlining” of CDC requirements for data reporting but said that it hoped that mandatory reporting would be phased out as soon as possible.

The association noted that this would require action by the Centers for Medicare & Medicaid Services. CMS now enforces the CDC requirements with a “condition of participation” (COP) provision, by which noncompliant hospitals could be excluded from Medicare. CMS has extended this COP to April 30, 2024, although it could choose to ask the Secretary of Health and Human Services to terminate it earlier.

If mandatory reporting were repealed, would most hospitals still report on the key COVID metrics? Mr. Demehin noted that before CMS implemented its COP, hospitals reported COVID data voluntarily, “and the participation rate was well over 90%. So setting up a mechanism similar to that is something we’ve encouraged CMS to consider.”

Dr. Eisenberg is skeptical. While bigger hospitals with more resources might continue reporting voluntarily, she said, safety-net hospitals in underserved areas might not, because they are especially short staffed. “Then you have disparities in which hospitals will report.”
 

Vaccinations: The sleeping dragon

COVID continues to ravage the nation. According to CDC statistics, there were 1,109 deaths from COVID in the U.S. in the week ending May 6, and total deaths have hit 1.13 million. There were 1,333 new COVID-related hospital admissions, and 7,261 people were in the hospital because of COVID.

Another eye-catching number: Only 16.9% of the U.S. population has received an updated COVID vaccine booster. Dr. Schaffner thinks that this is what we should really keep our eye on. While the combination of vaccinations and widespread SARS-CoV-2 infections has conferred herd immunity on most Americans, he said it’s temporary. “Whether your immunity comes from the virus and recovery from disease or from the vaccines, that immunity will wane over time. Unless we keep our vaccination rate up, we may see more future cases. We’ll have to see how that works out. But I’m nervous about that, because people do appear to be nonchalant.”

A version of this article first appeared on Medscape.com.

The first day of seeing patients without a mask was, for Sterling Ransone Jr., MD, “unsettling.” 

“I can’t tell you how weird it was the first day that I walked down the hall from my office to where my exam rooms are, to not have a mask on after 3 years of the habit,” said Dr. Ransone, a family physician in Deltaville, Va., and board chair of the American Academy of Family Physicians. 

The White House recently lifted the public health emergency order that overhauled the way health care providers operated and advised patients over the past 3 years. The new postpandemic era will require clinicians and staff to once again adjust. 

For Dr. Ransone, this transition entails getting used to his bare face, reminding patients of the latest and varying symptoms of the virus, and parting ways with sick patients if they refuse to wear a mask.

As states, hospitals, and health care systems around the country relax their mask mandates for care providers, clinicians will have to fall back on their own policies that patients with potential symptoms mask up. 

“Now that it’s up to our offices, we have to have a little bit more backbone,” Dr. Ransone said. “If they’re not willing to follow a health-related policy that will protect the vulnerable, we will not see them. And so for us, it’s been pretty straightforward.”

Despite the policy, Dr. Ransone has cared for patients who don’t disclose they are feeling sick until he enters the room. 

“And I wasn’t masked,” Dr. Ransone said. So, “I will wear masks for the rest of the day just to try to protect the rest of my patients in case I was exposed.”

Masks are optional for both patients and staff at the University of Maryland Medical System, but Niharika Khanna, MD, MBBS, said she still wears one with her patients, and her office advises staff to do the same. If patients are experiencing respiratory symptoms, like a cough, they are asked to wear one. 

“When the patient first walks up to you, you have no idea what they have,” Dr. Khanna said. 

Dr. Khanna is especially mindful of immunocompromised patients who have cancer, and Dr. Ransone cares for several patients who have received kidney transplants and are on potent immunosuppressive drugs. 

“I know they’re appreciating our efforts to protect them, and I think the other patients are realizing that it’s a wise thing to do,” Dr. Ransone said. 

Some patients have anxiety about the end of masking in doctor offices, but others have been excited about interacting more with their care teams, according to William Dahut, MD, chief scientific officer for the American Cancer Society. Many clinicians will advise their most immunocompromised patients the same as they did prior to the COVID-19 pandemic. 

“There’s always been guidelines that oncologists have given to patients who are immunocompromised – we always told them to avoid crowded places, crowded scenes, be outside more than inside,” Dr. Dahut said. “Those general recommendations will continue.”

The AAFP supports masking to limit COVID’s spread, but the “most important thing people can do is to get vaccinated,” Tochi Iroku-Malize, MD, MPH, MBA, president of the AAFP, said.

But the accessibility of vaccinations is also shifting.
 

Testing shifts

The government will continue to provide free COVID-19 vaccines because it still has supplies on hand. When this stock runs out, commercial insurance providers will be required to cover the immunizations, as they are considered preventive, but people without insurance will have to pay out of pocket. 

The AAFP is pushing the Biden administration and Congress to keep the purchase price of those vaccines low enough that clinicians can keep them in stock, according to Dr. Iroku-Malize. Once the federal government transitions COVID-19 vaccines to the commercial market – as early as later in 2023 – it may pose some challenges for providers. 

“If the price of the vaccines is too high, physician practices may struggle to make the upfront investment in COVID-19 vaccines,” Dr. Iroku-Malize said. “Patients often prefer to receive vaccine counseling and administration from their usual source of primary care, like their family physician.” 

The federal government has also said it still has a supply of treatments for the public to access for free, but has not revealed how much it has on hand or given a timeline for the transition to the private market. 

COVID-19 tests, meanwhile, are no longer covered because of the end of the public health emergency, and cost about $45 per kit on average, according to an analysis by the Kaiser Family Foundation.

Pediatrician Lisa Costello, MD, MPH, knows that price point will be a challenge for some families she cares for at West Virginia University Medicine Children’s Hospital in Morgantown. Many still ask her where they can access free tests. 

“Testing if you’re a higher risk person is something we need to ensure that people continue to be educated about,” Dr. Costello said. 

She’s hopeful that COVID-19 vaccines and treatments such as Paxlovid will stay free in the coming months so patients can continue to easily access them.
 

Future of telehealth

Relaxed regulations of prescribing controlled substances via telehealth and across state lines allowed clinicians to treat patients near and far during the pandemic. But many providers were worried about a proposal from the Drug Enforcement Administration to clamp down on the prescribing of controlled substances via telehealth, according to A. Mark Fendrick, MD, an internal medicine physician at the University of Michigan, Ann Arbor.

“We were all panicking about what was going to happen to what is for many clinicians a very valuable policy,” Dr. Fendrick said of the telehealth flexibilities introduced during COVID-19. 

The DEA, after getting 38,000 comments on their proposed regulations, pulled back on that plan, delaying the cliff until November. 

Dr. Fendrick said that telehealth has allowed clinicians to reach patients who have historically faced barriers to care, such as lacking transportation. 

“The benefits of that outweigh the potential harms,” he said. “Every policy you make that tightens access because you want to decrease the untoward and unfortunate outcomes will also decrease access to clinical indications.”

The AAFP said it hopes for clear guidance from the DEA in the coming months on what the new telehealth landscape for prescribing will look like.
 

Medicaid changes

About half of the patients who see Dr. Khanna have insurance through Medicaid. 

During the public health emergency, states were not allowed to remove anyone from Medicaid, regardless of whether they no longer qualified for the program or not. But a law passed by Congress last year requires states to once again check Medicaid eligibility. As many as 15 million people could lose their Medicaid coverage. 

That could affect the treatments Dr. Khanna recommends for her patients who get kicked off because those who become uninsured or transition to private insurance will have to pay more out of pocket. Maryland will start removals in June. 

“When you have an uninsured patient versus Medicaid, it’s a huge difference in what you can ask the patient to do – the medications you can provide, the testing you can provide,” Dr. Khanna said. 

States were authorized to remove people from Medicaid as of April 1, with Arkansas, New Hampshire, and South Dakota starting right away. But many states are just now getting the review process going. About a dozen states, including Indiana, Ohio, Utah, and West Virginia, started removing people in May 2023. 

Uninsurance rates hit record lows across the United States during the pandemic. Keeping Americans on health insurance is a top priority for the AAFP, Dr. Iroku-Malize said. “We know health care coverage disruptions prevent people from seeking and accessing the care they need.”

Many people who are removed from Medicaid will be eligible for health insurance through employers, or through the Affordable Care Act’s private marketplace. But premiums and deductibles are often higher in these plans, which studies have shown result in patients delaying medical visits and not filling prescriptions or receiving treatment.
 

Staying mindful

Hospitals that receive federal funds will still have to report COVID-19 test results to the Centers for Medicare & Medicaid Services through 2024, although private labs will no longer be obligated to do so. The Centers for Disease Control and Prevention will also continue to monitor virus levels in communities through wastewater. But some states will no longer collect data. 

Gone are the days when clinicians and others would watch for daily totals of case counts with the type of fervor typically reserved for live scoring updates during sports games, according to Dr. Costello.

“We just have to be mindful of the numbers that might be coming in,” Dr. Costello said.

Dr. Ransone, however, cautioned that clinicians not become complacent. In early May, Dr. Ransone saw two patients with conjunctivitis, what patients thought was simply pink eye – a symptom of the latest COVID-19 variant. Both patients told him it wasn’t possible they had COVID-19 because they didn’t have coughs. 

“I don’t want to see physician offices fall into that trap that it’s over and be a potential nidus for infection for other patients,” Dr. Ransone said. “It’s incumbent upon us to remind people of the current symptoms so that folks will know when they need to wear a mask when they’re around their grandmother.”

The move away from universal masking in the office has benefits. Many of his older patients have difficulty hearing and had used lip reading to help understand him, he said. During the pandemic, masks got in the way of that form of communication. Now they can see his mouth again and better decipher what he says.

“Being able to have that face-to-face contact, without a mask intervening, has been really beneficial for a lot of my older patients,” he said.

A version of this article first appeared on Medscape.com.

The first day of seeing patients without a mask was, for Sterling Ransone Jr., MD, “unsettling.” 

“I can’t tell you how weird it was the first day that I walked down the hall from my office to where my exam rooms are, to not have a mask on after 3 years of the habit,” said Dr. Ransone, a family physician in Deltaville, Va., and board chair of the American Academy of Family Physicians. 

The White House recently lifted the public health emergency order that overhauled the way health care providers operated and advised patients over the past 3 years. The new postpandemic era will require clinicians and staff to once again adjust. 

For Dr. Ransone, this transition entails getting used to his bare face, reminding patients of the latest and varying symptoms of the virus, and parting ways with sick patients if they refuse to wear a mask.

As states, hospitals, and health care systems around the country relax their mask mandates for care providers, clinicians will have to fall back on their own policies that patients with potential symptoms mask up. 

“Now that it’s up to our offices, we have to have a little bit more backbone,” Dr. Ransone said. “If they’re not willing to follow a health-related policy that will protect the vulnerable, we will not see them. And so for us, it’s been pretty straightforward.”

Despite the policy, Dr. Ransone has cared for patients who don’t disclose they are feeling sick until he enters the room. 

“And I wasn’t masked,” Dr. Ransone said. So, “I will wear masks for the rest of the day just to try to protect the rest of my patients in case I was exposed.”

Masks are optional for both patients and staff at the University of Maryland Medical System, but Niharika Khanna, MD, MBBS, said she still wears one with her patients, and her office advises staff to do the same. If patients are experiencing respiratory symptoms, like a cough, they are asked to wear one. 

“When the patient first walks up to you, you have no idea what they have,” Dr. Khanna said. 

Dr. Khanna is especially mindful of immunocompromised patients who have cancer, and Dr. Ransone cares for several patients who have received kidney transplants and are on potent immunosuppressive drugs. 

“I know they’re appreciating our efforts to protect them, and I think the other patients are realizing that it’s a wise thing to do,” Dr. Ransone said. 

Some patients have anxiety about the end of masking in doctor offices, but others have been excited about interacting more with their care teams, according to William Dahut, MD, chief scientific officer for the American Cancer Society. Many clinicians will advise their most immunocompromised patients the same as they did prior to the COVID-19 pandemic. 

“There’s always been guidelines that oncologists have given to patients who are immunocompromised – we always told them to avoid crowded places, crowded scenes, be outside more than inside,” Dr. Dahut said. “Those general recommendations will continue.”

The AAFP supports masking to limit COVID’s spread, but the “most important thing people can do is to get vaccinated,” Tochi Iroku-Malize, MD, MPH, MBA, president of the AAFP, said.

But the accessibility of vaccinations is also shifting.
 

Testing shifts

The government will continue to provide free COVID-19 vaccines because it still has supplies on hand. When this stock runs out, commercial insurance providers will be required to cover the immunizations, as they are considered preventive, but people without insurance will have to pay out of pocket. 

The AAFP is pushing the Biden administration and Congress to keep the purchase price of those vaccines low enough that clinicians can keep them in stock, according to Dr. Iroku-Malize. Once the federal government transitions COVID-19 vaccines to the commercial market – as early as later in 2023 – it may pose some challenges for providers. 

“If the price of the vaccines is too high, physician practices may struggle to make the upfront investment in COVID-19 vaccines,” Dr. Iroku-Malize said. “Patients often prefer to receive vaccine counseling and administration from their usual source of primary care, like their family physician.” 

The federal government has also said it still has a supply of treatments for the public to access for free, but has not revealed how much it has on hand or given a timeline for the transition to the private market. 

COVID-19 tests, meanwhile, are no longer covered because of the end of the public health emergency, and cost about $45 per kit on average, according to an analysis by the Kaiser Family Foundation.

Pediatrician Lisa Costello, MD, MPH, knows that price point will be a challenge for some families she cares for at West Virginia University Medicine Children’s Hospital in Morgantown. Many still ask her where they can access free tests. 

“Testing if you’re a higher risk person is something we need to ensure that people continue to be educated about,” Dr. Costello said. 

She’s hopeful that COVID-19 vaccines and treatments such as Paxlovid will stay free in the coming months so patients can continue to easily access them.
 

Future of telehealth

Relaxed regulations of prescribing controlled substances via telehealth and across state lines allowed clinicians to treat patients near and far during the pandemic. But many providers were worried about a proposal from the Drug Enforcement Administration to clamp down on the prescribing of controlled substances via telehealth, according to A. Mark Fendrick, MD, an internal medicine physician at the University of Michigan, Ann Arbor.

“We were all panicking about what was going to happen to what is for many clinicians a very valuable policy,” Dr. Fendrick said of the telehealth flexibilities introduced during COVID-19. 

The DEA, after getting 38,000 comments on their proposed regulations, pulled back on that plan, delaying the cliff until November. 

Dr. Fendrick said that telehealth has allowed clinicians to reach patients who have historically faced barriers to care, such as lacking transportation. 

“The benefits of that outweigh the potential harms,” he said. “Every policy you make that tightens access because you want to decrease the untoward and unfortunate outcomes will also decrease access to clinical indications.”

The AAFP said it hopes for clear guidance from the DEA in the coming months on what the new telehealth landscape for prescribing will look like.
 

Medicaid changes

About half of the patients who see Dr. Khanna have insurance through Medicaid. 

During the public health emergency, states were not allowed to remove anyone from Medicaid, regardless of whether they no longer qualified for the program or not. But a law passed by Congress last year requires states to once again check Medicaid eligibility. As many as 15 million people could lose their Medicaid coverage. 

That could affect the treatments Dr. Khanna recommends for her patients who get kicked off because those who become uninsured or transition to private insurance will have to pay more out of pocket. Maryland will start removals in June. 

“When you have an uninsured patient versus Medicaid, it’s a huge difference in what you can ask the patient to do – the medications you can provide, the testing you can provide,” Dr. Khanna said. 

States were authorized to remove people from Medicaid as of April 1, with Arkansas, New Hampshire, and South Dakota starting right away. But many states are just now getting the review process going. About a dozen states, including Indiana, Ohio, Utah, and West Virginia, started removing people in May 2023. 

Uninsurance rates hit record lows across the United States during the pandemic. Keeping Americans on health insurance is a top priority for the AAFP, Dr. Iroku-Malize said. “We know health care coverage disruptions prevent people from seeking and accessing the care they need.”

Many people who are removed from Medicaid will be eligible for health insurance through employers, or through the Affordable Care Act’s private marketplace. But premiums and deductibles are often higher in these plans, which studies have shown result in patients delaying medical visits and not filling prescriptions or receiving treatment.
 

Staying mindful

Hospitals that receive federal funds will still have to report COVID-19 test results to the Centers for Medicare & Medicaid Services through 2024, although private labs will no longer be obligated to do so. The Centers for Disease Control and Prevention will also continue to monitor virus levels in communities through wastewater. But some states will no longer collect data. 

Gone are the days when clinicians and others would watch for daily totals of case counts with the type of fervor typically reserved for live scoring updates during sports games, according to Dr. Costello.

“We just have to be mindful of the numbers that might be coming in,” Dr. Costello said.

Dr. Ransone, however, cautioned that clinicians not become complacent. In early May, Dr. Ransone saw two patients with conjunctivitis, what patients thought was simply pink eye – a symptom of the latest COVID-19 variant. Both patients told him it wasn’t possible they had COVID-19 because they didn’t have coughs. 

“I don’t want to see physician offices fall into that trap that it’s over and be a potential nidus for infection for other patients,” Dr. Ransone said. “It’s incumbent upon us to remind people of the current symptoms so that folks will know when they need to wear a mask when they’re around their grandmother.”

The move away from universal masking in the office has benefits. Many of his older patients have difficulty hearing and had used lip reading to help understand him, he said. During the pandemic, masks got in the way of that form of communication. Now they can see his mouth again and better decipher what he says.

“Being able to have that face-to-face contact, without a mask intervening, has been really beneficial for a lot of my older patients,” he said.

A version of this article first appeared on Medscape.com.

The first day of seeing patients without a mask was, for Sterling Ransone Jr., MD, “unsettling.” 

“I can’t tell you how weird it was the first day that I walked down the hall from my office to where my exam rooms are, to not have a mask on after 3 years of the habit,” said Dr. Ransone, a family physician in Deltaville, Va., and board chair of the American Academy of Family Physicians. 

The White House recently lifted the public health emergency order that overhauled the way health care providers operated and advised patients over the past 3 years. The new postpandemic era will require clinicians and staff to once again adjust. 

For Dr. Ransone, this transition entails getting used to his bare face, reminding patients of the latest and varying symptoms of the virus, and parting ways with sick patients if they refuse to wear a mask.

As states, hospitals, and health care systems around the country relax their mask mandates for care providers, clinicians will have to fall back on their own policies that patients with potential symptoms mask up. 

“Now that it’s up to our offices, we have to have a little bit more backbone,” Dr. Ransone said. “If they’re not willing to follow a health-related policy that will protect the vulnerable, we will not see them. And so for us, it’s been pretty straightforward.”

Despite the policy, Dr. Ransone has cared for patients who don’t disclose they are feeling sick until he enters the room. 

“And I wasn’t masked,” Dr. Ransone said. So, “I will wear masks for the rest of the day just to try to protect the rest of my patients in case I was exposed.”

Masks are optional for both patients and staff at the University of Maryland Medical System, but Niharika Khanna, MD, MBBS, said she still wears one with her patients, and her office advises staff to do the same. If patients are experiencing respiratory symptoms, like a cough, they are asked to wear one. 

“When the patient first walks up to you, you have no idea what they have,” Dr. Khanna said. 

Dr. Khanna is especially mindful of immunocompromised patients who have cancer, and Dr. Ransone cares for several patients who have received kidney transplants and are on potent immunosuppressive drugs. 

“I know they’re appreciating our efforts to protect them, and I think the other patients are realizing that it’s a wise thing to do,” Dr. Ransone said. 

Some patients have anxiety about the end of masking in doctor offices, but others have been excited about interacting more with their care teams, according to William Dahut, MD, chief scientific officer for the American Cancer Society. Many clinicians will advise their most immunocompromised patients the same as they did prior to the COVID-19 pandemic. 

“There’s always been guidelines that oncologists have given to patients who are immunocompromised – we always told them to avoid crowded places, crowded scenes, be outside more than inside,” Dr. Dahut said. “Those general recommendations will continue.”

The AAFP supports masking to limit COVID’s spread, but the “most important thing people can do is to get vaccinated,” Tochi Iroku-Malize, MD, MPH, MBA, president of the AAFP, said.

But the accessibility of vaccinations is also shifting.
 

Testing shifts

The government will continue to provide free COVID-19 vaccines because it still has supplies on hand. When this stock runs out, commercial insurance providers will be required to cover the immunizations, as they are considered preventive, but people without insurance will have to pay out of pocket. 

The AAFP is pushing the Biden administration and Congress to keep the purchase price of those vaccines low enough that clinicians can keep them in stock, according to Dr. Iroku-Malize. Once the federal government transitions COVID-19 vaccines to the commercial market – as early as later in 2023 – it may pose some challenges for providers. 

“If the price of the vaccines is too high, physician practices may struggle to make the upfront investment in COVID-19 vaccines,” Dr. Iroku-Malize said. “Patients often prefer to receive vaccine counseling and administration from their usual source of primary care, like their family physician.” 

The federal government has also said it still has a supply of treatments for the public to access for free, but has not revealed how much it has on hand or given a timeline for the transition to the private market. 

COVID-19 tests, meanwhile, are no longer covered because of the end of the public health emergency, and cost about $45 per kit on average, according to an analysis by the Kaiser Family Foundation.

Pediatrician Lisa Costello, MD, MPH, knows that price point will be a challenge for some families she cares for at West Virginia University Medicine Children’s Hospital in Morgantown. Many still ask her where they can access free tests. 

“Testing if you’re a higher risk person is something we need to ensure that people continue to be educated about,” Dr. Costello said. 

She’s hopeful that COVID-19 vaccines and treatments such as Paxlovid will stay free in the coming months so patients can continue to easily access them.
 

Future of telehealth

Relaxed regulations of prescribing controlled substances via telehealth and across state lines allowed clinicians to treat patients near and far during the pandemic. But many providers were worried about a proposal from the Drug Enforcement Administration to clamp down on the prescribing of controlled substances via telehealth, according to A. Mark Fendrick, MD, an internal medicine physician at the University of Michigan, Ann Arbor.

“We were all panicking about what was going to happen to what is for many clinicians a very valuable policy,” Dr. Fendrick said of the telehealth flexibilities introduced during COVID-19. 

The DEA, after getting 38,000 comments on their proposed regulations, pulled back on that plan, delaying the cliff until November. 

Dr. Fendrick said that telehealth has allowed clinicians to reach patients who have historically faced barriers to care, such as lacking transportation. 

“The benefits of that outweigh the potential harms,” he said. “Every policy you make that tightens access because you want to decrease the untoward and unfortunate outcomes will also decrease access to clinical indications.”

The AAFP said it hopes for clear guidance from the DEA in the coming months on what the new telehealth landscape for prescribing will look like.
 

Medicaid changes

About half of the patients who see Dr. Khanna have insurance through Medicaid. 

During the public health emergency, states were not allowed to remove anyone from Medicaid, regardless of whether they no longer qualified for the program or not. But a law passed by Congress last year requires states to once again check Medicaid eligibility. As many as 15 million people could lose their Medicaid coverage. 

That could affect the treatments Dr. Khanna recommends for her patients who get kicked off because those who become uninsured or transition to private insurance will have to pay more out of pocket. Maryland will start removals in June. 

“When you have an uninsured patient versus Medicaid, it’s a huge difference in what you can ask the patient to do – the medications you can provide, the testing you can provide,” Dr. Khanna said. 

States were authorized to remove people from Medicaid as of April 1, with Arkansas, New Hampshire, and South Dakota starting right away. But many states are just now getting the review process going. About a dozen states, including Indiana, Ohio, Utah, and West Virginia, started removing people in May 2023. 

Uninsurance rates hit record lows across the United States during the pandemic. Keeping Americans on health insurance is a top priority for the AAFP, Dr. Iroku-Malize said. “We know health care coverage disruptions prevent people from seeking and accessing the care they need.”

Many people who are removed from Medicaid will be eligible for health insurance through employers, or through the Affordable Care Act’s private marketplace. But premiums and deductibles are often higher in these plans, which studies have shown result in patients delaying medical visits and not filling prescriptions or receiving treatment.
 

Staying mindful

Hospitals that receive federal funds will still have to report COVID-19 test results to the Centers for Medicare & Medicaid Services through 2024, although private labs will no longer be obligated to do so. The Centers for Disease Control and Prevention will also continue to monitor virus levels in communities through wastewater. But some states will no longer collect data. 

Gone are the days when clinicians and others would watch for daily totals of case counts with the type of fervor typically reserved for live scoring updates during sports games, according to Dr. Costello.

“We just have to be mindful of the numbers that might be coming in,” Dr. Costello said.

Dr. Ransone, however, cautioned that clinicians not become complacent. In early May, Dr. Ransone saw two patients with conjunctivitis, what patients thought was simply pink eye – a symptom of the latest COVID-19 variant. Both patients told him it wasn’t possible they had COVID-19 because they didn’t have coughs. 

“I don’t want to see physician offices fall into that trap that it’s over and be a potential nidus for infection for other patients,” Dr. Ransone said. “It’s incumbent upon us to remind people of the current symptoms so that folks will know when they need to wear a mask when they’re around their grandmother.”

The move away from universal masking in the office has benefits. Many of his older patients have difficulty hearing and had used lip reading to help understand him, he said. During the pandemic, masks got in the way of that form of communication. Now they can see his mouth again and better decipher what he says.

“Being able to have that face-to-face contact, without a mask intervening, has been really beneficial for a lot of my older patients,” he said.

A version of this article first appeared on Medscape.com.

Hyperbaric oxygen therapy (HBOT) increased markers of heart function in a small randomized, controlled trial of patients with long COVID.

Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.

GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.

The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.

“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.

“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.

“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”

Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
 

Biomarker changes

The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.

Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.

The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.

The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.

At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.

The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.

In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.

In addition, GWE increased overall after HBOT from 96.3 to 97.1.

Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.

After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
 

Clinical relevance unclear

Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.

“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”

That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”

Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”

“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”

Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”

The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hyperbaric oxygen therapy (HBOT) increased markers of heart function in a small randomized, controlled trial of patients with long COVID.

Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.

GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.

The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.

“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.

“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.

“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”

Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
 

Biomarker changes

The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.

Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.

The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.

The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.

At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.

The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.

In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.

In addition, GWE increased overall after HBOT from 96.3 to 97.1.

Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.

After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
 

Clinical relevance unclear

Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.

“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”

That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”

Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”

“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”

Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”

The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hyperbaric oxygen therapy (HBOT) increased markers of heart function in a small randomized, controlled trial of patients with long COVID.

Patients with reduced left ventricular global longitudinal strain (GLS) at baseline who received HBOT had a significant increase in GLS, compared with those who received sham treatment.

GLS is a measure of systolic function that is thought to be a predictor of heart failure–related outcomes.

The study also showed that global work efficiency (GWE) and the global work index (GWI) increased in HBOT-treated patients, though not significantly.

“HBOT is an effective treatment for diabetic foot ulcers, decompression sickness in divers, and other conditions, such as cognitive impairment after stroke,” Marina Leitman, MD, of the Sackler School of Medicine, Tel Aviv, said in an interview. Her team also studied HBOT in asymptomatic older patients and found that the treatment seemed to improve left ventricular end systolic function.

“We should open our minds to thinking about this treatment for another indication,” she said. “That is the basis of precision medicine. We have this treatment and know it can be effective for cardiac pathology.

“Now we can say that post-COVID syndrome patients probably should be evaluated with echocardiography and GLS, which is the main parameter that showed improvement in our study,” she added. “If GLS is below normal values, these patients can benefit from HBOT, although additional research is needed to determine the optimal number of sessions.”

Dr. Leitman presented the study at the European Association of Cardiovascular Imaging 2023, a scientific congress of the European Society of Cardiology.
 

Biomarker changes

The study enrolled 60 hospitalized and nonhospitalized post-COVID syndrome patients with ongoing symptoms for at least 3 months after having mild to moderate symptomatic COVID-19.

Participants were randomized to receive HBOT or a sham procedure five times per week for 8 weeks, for a total of 40 sessions. They underwent echocardiography at baseline and 1-3 weeks after the final session to assess GLS.

The HBOT group received 100% oxygen through a mask at a pressure of two atmospheres for 90 minutes, with 5-minute air breaks every 20 minutes.

The sham group received 21% oxygen by mask at one atmosphere for 90 minutes.

At baseline, 29 participants (48%) had reduced GLS, despite having a normal ejection fraction, Dr. Leitman said. Of those, 16 (53%) were in the HBOT group and 13 (43%) were in the sham group.

The average GLS at baseline across all participants was –17.8%; a normal value is about –20%.

In the HBOT group, GLS increased significantly from –17.8% at baseline to –20.2% after HBOT. In the sham group, GLS was –17.8% at baseline and –19.1% at the end of the study, with no statistically significant difference between the two measurements.

In addition, GWE increased overall after HBOT from 96.3 to 97.1.

Dr. Leitman’s poster showed GLS and myocardial work indices before and after HBOT in a 45-year-old patient. Prior to treatment, GLS was –19%; GWE was 96%; and GWI was 1,833 mm Hg.

After HBOT treatment, GLS was –22%; GWE, 98%; and GWI, 1,911 mm Hg.
 

Clinical relevance unclear

Scott Gorenstein, MD, associate professor in the department of surgery and medical director of wound care and hyperbaric medicine at NYU Langone–Long Island, New York, commented on the study for this news organization.

“The approach certainly warrants studying, but the benefit is difficult to assess,” he said. “We still don’t understand the mechanism of long COVID, so it’s difficult to go from there to say that HBOT will be an effective therapy.”

That said, he added, “This is probably the best study I’ve seen in that it’s a randomized controlled trial, rather than a case series.”

Nevertheless, he noted, “We have no idea from this study whether the change in GLS is clinically relevant. As a clinician, I can’t now say that HBOT is going to improve heart failure secondary to long COVID. We don’t know whether the participants were New York heart failure class 3 or 4, for example, and all of a sudden went from really sick to really good.”

“There are many interventions that may change markers of cardiac function or inflammation,” he said. “But if they don’t make a difference in quantity or quality of life, is the treatment really valuable?”

Dr. Gorenstein said he would have no problem treating a patient with mild to moderate COVID-related heart failure with HBOT, since his own team’s study conducted near the outset of the pandemic showed it was safe. “But HBOT is an expensive treatment in the U.S. and there still are some risks and side effects, albeit very, very low.”

The study received no funding. Dr. Leitman and Dr. Gorenstein have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

Throughout the COVID-19 pandemic, health care professionals (HCPs), including emergency medicine physicians and hospitalists, have been continuously challenged to maintain an up-to-date clinical practice on COVID-19 therapeutics as new evidence emerged.^1,2 In the early part of the pandemic, these included not only appropriate and time-sensitive prescriptions of COVID-19 therapeutics, such as remdesivir and dexamethasone, but also judicious use of empiric antibiotics given the low prevalence for bacterial coinfection in early disease.^3-6 Alongside this, curbing the excessive laboratory testing of these patients during the pandemic was important not only to minimize costs but also to reduce potential iatrogenic harm and extended length of stay (LOS).⁷

At the beginning of the pandemic in March 2020 at the US Department of Veterans Affairs (VA) North Texas Health Care System (VANTHCS) Dallas VA Medical Center (DVAMC), we attempted to provide therapeutic guidance for physicians primarily through direct infectious disease (ID) consultation (in-person or electronic).⁸ This was secondarily supported by a pharmacist and ID physician–curated “living guidance” document on COVID-19 care accessible to all physicians through the DVAMC electronic health record (EHR) and intranet.

As the alpha variant (lineage B.1.1.7) of COVID-19 began spreading throughout North Texas in the winter of 2020, we implemented a targeted educational intervention toward the hospitalist group taking care of patients with COVID-19 with the primary goal of improving the accuracy of COVID-19 therapeutics while minimizing the consultative burden on ID clinical and pharmacy staff. This initiative consisted of (1) proactive guideline dissemination through email and text messages; (2) virtual didactics; and (3) physician reminders during the consultation process. Our ultimate aims were to improve hospitalist-led appropriate prescriptions of remdesivir and dexamethasone, reducing empiric antibiotic days of therapy in patients with COVID-19 at low risk of bacterial coinfection, and reducing laboratory orders that were not indicated for the management of these patients. Following this intervention and the resolution of the second wave, we retrospectively assessed the temporal trends of COVID-19 practices by hospitalists and associated patterns of ID consultation in the DVAMC from October 1, 2020, to March 31, 2021.

METHODS

The educational intervention was carried out at the DVAMC, a 1A high complex facility with more than 200 inpatient beds and part of the VANTHCS. During the study period, patients admitted with COVID-19 were located either on a closed floor (managed by the hospitalist team) or in a closed intensive care unit (ICU) (managed by the pulmonary/critical care team) contingent on the level of care or oxygen supplementation required. ID and other subspecialties provided consultation services as requested by hospitalists or ICU teams either electronically or in person. During the study period, 66 hospitalists were involved in the care of the patients: 59 (89.5%) permanent staff, 4 (6.0%) fee-basis physicians, and 3 (4.5%) moonlighting fellows.

Educational Initiative

We delivered educational sessions to the hospitalists, using collaboration software with video meeting capability every 1 to 2 months beginning in December 2020. An additional session focused on reducing empiric antibiotic prescriptions was also delivered to the emergency medicine department, based on feedback from the hospitalist group. The content for the educational sessions came from informal surveys of both ID trainees assigned to the consultation service and hospitalists, covering the following topics: understanding the stages of COVID-19 illness (virologic replication vs inflammatory) and rationales for therapy; assessing disease severity; indications and use of remdesivir; indications and use of dexamethasone; assessing for bacterial coinfections; when an ID consultation is required; management algorithm for COVID-19; and locating guidelines on the intranet. About 15 to 20 physicians participated in each session. In addition, slides of these didactics and updated institutional COVID-19 guidelines were disseminated to the hospitalist group via email and text messaging. We also linked the intranet institution guidelines in our communication, including a revised user-friendly flowchart (eAppendix).

Laboratory Stewardship Initiative

Laboratory stewardship initiatives were implemented by modifying suggested orders on the admission of patients with COVID-19 and directly educating hospitalist and emergency medicine physicians on evidence-based laboratory orders. At the beginning of the pandemic, a broad admission order set was established at DVAMC, based on the then limited knowledge of the course of infection with COVID-19. This order set allowed the admitting physicians to efficiently order laboratory tests for patients, especially during the demanding increase in patient volume experienced by DVAMC.

As new evidence emerged during the pandemic, many of the laboratory orders were reviewed for clinical utility during care for the patient with COVID-19 per the latest guidance. In December 2020, the admission orders for patients with COVID-19 were revised to reflect better laboratory stewardship to reduce cost and harm. The ID section revised the laboratory orders and disseminated the new order set to admitting physicians. Specifically, the admission order set removed the following laboratory tests available for selection: routine blood cultures, interleukin 6 (IL-6) level, and Legionella sputum culture. These laboratory orders were removed based on the lack of supporting evidence in persons admitted with COVID-19.⁹ In addition to modification of the admission order set, educational sessions were held with hospitalists to disseminate knowledge of the new changes and address any concerns.

Observations of Care

This study was approved by the VANTHCS Institutional Review Board (protocol code 20-047). Records were retrospectively reviewed for patients admitted to DVAMC for COVID-19 under hospitalist care (patients admitted directly to the ICU were excluded) from October 1, 2020, to March 31, 2021. Age, sex, race and ethnicity, and comorbidities were collected from the EHR. In addition clinical measures such as maximum oxygen requirement during admission (none, nasal cannula of 2-4 L/min, high flow/bilevel positive airway pressure [BiPAP] or mechanical ventilation), proven presence of coinfection (defined as the isolation of a probable pathogen in pure culture and/or clinically determined by ID specialist evaluation), and the average LOS also were collected. For laboratory stewardship data, a retrospective chart review was conducted to determine the total number of blood cultures obtained within 24 hours of admission per month during the study period. Both IL-6 levels and Legionella sputum culture data were collected as the total number of laboratory orders per month, as it was assumed that most of these orders were obtained for patients admitted with COVID-19.

Individual patient-level data were extracted to calculate monthly percentages of ID consultations for COVID-19 by the hospitalist team, adherence to institutional guidelines for dexamethasone and remdesivir prescriptions, and empiric antibiotic prescriptions for patients with COVID-19, including use of a priori adjudication criteria to determine justified vs unjustified empiric use. These criteria included asymmetric chest X-ray infiltrates concerning for bacterial pneumonia; peripheral white blood cell count > 11 K/μL; critical respiratory failure in the emergency department (ED) and being transferred to the ICU; and ID consultation recommended. Because the total number of antibiotics was not being analyzed but rather just the use of antibiotics for the justified and unjustified groups, antibiotic days were reported as the length of therapy (LOT).¹⁰ A subset analysis was performed on antibiotic prescriptions by the hospitalist group focusing on those with mild-to-moderate oxygen requirements (no high flow, noninvasive or invasive ventilatory methods) and excluding infections with a proven microbiologic entity.

Differences in demographic and clinical characteristics of patients with COVID-19 admitted from October 1, 2020, to March 31, 2021, were assessed using ANOVA, χ², and Kruskal-Wallis test. χ² was used to compare the difference in total laboratory orders for routine blood cultures, IL-6 levels, and Legionella sputum cultures between pre-intervention (October to December 2020) and postintervention (January to March 2021). These pre- and postintervention periods were determined based on the timing of revised admission orders in the EHR and initiation of focused educational sessions starting in late December 2020 and early January 2021. Linear regressions were used to examine the possible 6-month trend of the percentage of patients receiving ID consultation for appropriate dexamethasone prescriptions, appropriate remdesivir prescriptions, appropriate antibiotic coadministration, and mean number of antibiotic days per patient. Linear and logistic regression were also used to assess the trend in LOS over the 6 months while adjusting for age, race and ethnicity, sex, and coinfections. All analyses were performed using SAS 9.4. Statistical significance was defined as P < .05.

RESULTS

From October 1, 2020, to March 31, 2021, there were 565 admissions for COVID-19, which peaked in January 2021 with 163. Analysis of the patient characteristics showed no statistically significant difference for age, sex, oxygen requirements during admission, or proven presence of coinfection between the months of interest (Table 1).

The number of blood cultures obtained in the first 24 hours of admission significantly decreased from 58.1% of admissions in October 2020 to 34.8% of admissions in March 2021 (P < .01) (Table 2).

DISCUSSION

As the COVID-19 pandemic has evolved, the ability to enact up-to-date guidance is crucial to streamlining patient care, improving time to COVID-19–specific therapies, and minimizing the burden on subspecialty consultation services. At DVAMC, we initiated a targeted and deliberate educational effort directed toward hospitalist and ED groups combined with a laboratory stewardship effort over 6 months to improve the implementation of COVID-19 therapeutics, reduce empiric antibiotic use without reliance on ID consultation services, and reduce the number of unnecessary laboratory orders for admitted patients with COVID-19. During this time, we observed modest but statistically significant improvements in the accuracy of dexamethasone and remdesivir prescribing. In addition, we observed statistically significant improvement in the average LOT per patient regarding antibiotic use and overall decreased LOS. These improvements were seen in parallel with decreasing requests for ID consultation, suggesting that they were attributable in part to increasing self-confidence and efficacy in COVID-19 practices by the hospitalist group. Modification of the COVID-19 admission order set for our facility resulted in substantial decreases in orders for blood cultures, IL-6 levels, and sputum cultures for Legionella.

ID consultation, either in person or remotely, has been instrumental in assisting physicians in COVID-19 management and has been shown to reduce morbidity, mortality, and patient LOS in other infections.^11,12 However, in scenarios where ID consultation is not available or in limited supply, accessibility, familiarity, and confidence of primary practitioners to use therapeutic guidance material are integral. Frequent and accessible guidance for the management of COVID-19 has been provided by the National Institutes of Health and the Infectious Diseases Society of America.^13,14 Other mechanisms of assisting physicians in both test ordering and therapeutics include clinical decision support tools built into the EHR and the use of a smartphone digital application.¹⁵ Guidance needs to be adapted to the context of the facility, including available resources and specific restrictions and/or prohibitions on therapeutics (eg, mandatory ID consultation or approval). In our facility, while COVID-19 therapeutic living guidance documents were maintained and accessible through the intranet, proactive dissemination and redirection were important steps in enabling the use of these documents.

Limitations

We acknowledge several limitations to this study. Most important, the correlations we observed do not represent causation. Our analysis was not designed to ascertain the direct impact of any single or combined educational and laboratory stewardship intervention from this study, and we acknowledge that the improvements in part could be related to increased experience and confidence with COVID-19 management that occurred over time independent of our programs. Furthermore, we acknowledge that several areas of COVID-19 management did not improve over time (such as overall empiric antibiotic use from the ED) or had very modest improvements (hospitalist-initiated remdesivir use). These results underscore the complex dynamics and contextual barriers to rapidly implementing guideline-based care at VANTHCS. Potential factors include insufficient reach to all physicians, variable learner motivation, and therapeutic momentum of antibiotic use carried forward from the ED.^16,17 These factors should be considered as grounds for further study. Another limitation was the inability to track viewership and engagement of our COVID-19 guidance document. Without the use metrics, it is difficult to know the individual impact of the document regarding the changing trends in COVID-19 management we observed during the study period.

Conclusions

We report improvements in COVID-19 therapeutic prescriptions and the use of antibiotics and laboratory testing over 6 months at the DVAMC. This was correlated with a deliberate COVID-19 educational initiative that included antibiotic and laboratory stewardship interventions with simultaneous decreased reliance on ID consultation. These efforts lend support to the proof of the principle of combined educational and laboratory stewardship interventions to improve the care of COVID-19 patients, especially where ID support may not be available or is accessed remotely.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

To the Editor:

Pemphigoid gestationis (PG), or gestational pemphigoid, is a rare autoimmune bullous disease (AIBD) occurring in 1 in 50,000 pregnancies. It is characterized by abrupt development of intensely pruritic papules and urticarial plaques, followed by an eruption of blisters.¹ We present a case of new-onset PG that erupted 10 days following SARs-CoV-2 messenger RNA (mRNA) vaccination with BNT162b2 (Pfizer-BioNTech).

A 36-year-old pregnant woman (gravida 1, para 0, aborta 0) at 37 weeks’ gestation presented to our AIBD clinic with a pruritic dermatitis of 6 weeks’ duration that developed 10 days after receiving the second dose of BNT162b2. Multiple intensely pruritic, red bumps presented first on the forearms and within days spread to the thighs, hands, and abdomen, followed by progression to the ankles, feet, and back 2 weeks later. An initial biopsy was consistent with subacute spongiotic dermatitis with rare eosinophils. She found minimal relief from diphenhydramine or topical steroids. She denied oral, nasal, ocular, or genital involvement or history of any other skin disease. The pregnancy had been otherwise uneventful.

Physical examination revealed annular edematous plaques on the trunk and buttocks; excoriated and erythematous papules on the neck, trunk, arms, and legs; and scattered vesicles along the fingers, arms, hands, abdomen, back, legs, and feet (Figure 1). The Bullous Pemphigoid Disease Area Index (BPDAI) total skin activity score was 25.3, corresponding to moderate disease activity (validated at 20–56).² The BPDAI total pruritus component score was 20. A repeat biopsy for direct immunofluorescence showed faint linear deposits of IgG and bright linear deposits of C3 along the basement membrane zone. Indirect immunofluorescence showed linear deposits of IgG localized to the blister roof of salt-split skin at a dilution of 1:40. An enzyme-linked immunosorbent assay for anti-BP180 was 62 U/mL (negative, <9 U/mL; positive, ≥9 U/mL), and anti-BP230 autoantibodies were less than 9 U/mL (negative <9 U/mL; positive, ≥9 U/mL). Given these clinical and histopathologic findings, PG was diagnosed. 

The patient was started on prednisone 20 mg and antihistamines while continuing topical steroids. Pruritus and blistering improved close to delivery. Fetal monitoring with regular biophysical profiles remained normal. The patient delivered a healthy neonate without skin lesions at 40 weeks’ gestation. The disease flared 2 days after delivery, and prednisone was increased to 40 mg and slowly tapered. Two months after delivery, the patient remained on prednisone 10 mg daily with ongoing but reduced blistering and pruritus (Figure 2). The BPDAI total skin activity and pruritus component scores remained elevated at 20.3 and 14, respectively, and anti-BP180 was 44 U/mL. After a discussion with the patient on safe systemic therapy while breastfeeding, intravenous immunoglobulin (IVIG) was initiated. The patient received 3 monthly infusions at 2 g/kg and was able to taper the prednisone to 5 mg every other day without new lesions. Four months after completion of IVIG therapy, she achieved complete remission off all therapy.

Management of PG begins with topical corticosteroids, but most patients require systemic steroid therapy.¹ Remission commonly occurs close to delivery, and 75% of patients flare post partum, though the disease typically resolves 6 months following delivery.^1,3,4 For persistent intrapartum cases requiring more than prednisone 20 mg daily, therapy can include dapsone, IVIG, azathioprine, rituximab, or plasmapheresis.^4,5 Dapsone and IVIG are compatible with breastfeeding postpartum, but if dapsone is selected, the infant must be monitored for hemolytic anemia.⁵ Pemphigoid gestationis increases the risk for a premature or small-for-gestational-age neonate, necessitating regular fetal monitoring until delivery.¹ Cutaneous lesions may affect the newborn, though this occurrence is rare and self-limiting.⁶Pemphigoid gestationis may recur in subsequent pregnancies at a rate of 33% to 55%, with earlier and more severe presentations.⁴

Clinically and histologically, PG closely resembles bullous pemphigoid (BP), but the exact pathogenesis is not fully understood. Recently, another case of what was termed pseudo-PG has been described 3 days following administration of the second dose of the Pfizer-BioNTech COVID-19 vaccine.⁷ Since the introduction of COVID-19 mRNA vaccines, cases of postvaccination BP, BP-like eruptions, and pemphigus vulgaris have been described.^8-11 Tomayko et al¹⁰ reported 12 cases of subepidermal eruptions, including BP, in which 7 patients developed blisters after the second dose of either the Pfizer-BioNTech or Moderna mRNA vaccine. Three patients who developed BP after the first dose of the vaccine and chose to receive the second dose tolerated it well, with a mild flare observed in 1 patient.¹⁰ Similarly, subsequent vaccine doses in reports of vaccine-associated AIBD resulted in increased disease activity in 21% of cases.¹² COVID-19 vaccine–associated BP, similar to drug-induced BP, seemingly displays a milder course of disease compared to the classic form of BP.^10,13 More follow-up is needed to better understand these reactions and inform appropriate discussions on the administration of booster doses. Currently, completion of the vaccination series against COVID-19 is advisable given the paucity of reports of postvaccination AIBD and the risk for COVID-19 infection, but careful discussions on a case-by-case basis are warranted related to the risk for disease exacerbation following subsequent vaccinations.

The clinical presentation and diagnostic evaluation of our patient’s rash were consistent with PG. The temporal relationship between vaccine administration and PG lesion onset suggests the mRNA vaccine triggered AIBD in our patient. Interestingly, AIBD associated with COVID-19 is not unique to only the vaccines and has been observed following infection with the virus itself.¹⁴ The high rate of vaccination against COVID-19 in contrast with the low number of reported cases of AIBD after vaccination supports the overall safety of COVID-19 vaccines but identifies a need for further understanding of the processes that lead to the development of autoimmune conditions in at-risk populations.

The Centers for Disease Control and Prevention and the U.S. Census Bureau estimate that 6.1% of the U.S. adult population is living with long COVID, with millions more debilitated worldwide. The demand for substantial treatment is enormous, but the urgency to fund and begin the necessary range of clinical trials has not met the severity of the problem.
 

While trials are slowly beginning to happen, the treatment choices and trial design require crucial nuances and understanding of viral-onset illnesses, and few research groups are creating strong trials that fully reflect the complexities of this landscape.

This article aims to share key considerations and best practices that are essential to the success of these trials. These recommendations recognize that roughly half of long COVID patients have new-onset myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia from COVID, which must be at the forefront of how trials are designed and conducted, and are additionally based on the current hypotheses about long COVID’s pathophysiologies. 
 

1: Drugs proposed by experts in postviral fields should be prioritized

Upward of 50 drugs for viral-onset conditions like ME/CFS, dysautonomia, AIDS, and others have been waiting for years to go to trial, but have not had the funding to do so. 

Treatments proposed by experts in viral-onset illnesses (such as ME/CFS and dysautonomia) should be prioritized (PM R. 2022 Oct;14[10]:1270-91), as outside researchers are not familiar with these fields and their potential treatment options.
 

2: Drugs targeting a wide range of mechanisms should be trialed

Treatments that should be trialed include anticoagulants/antiplatelets for clotting and vascular functioning, immunomodulators including JAK-STAT inhibitors, COVID-specific antivirals and antivirals against reactivated herpesviruses (Valcyte, Valacyclovir, EBV vaccine). 

Other options include prescription mast cell stabilizers (ketotifen, cromolyn sodium), drugs that regulate microglial activation (low-dose naltrexone, low-dose aripiprazole), anti-CGRP medications, beta-blockers, and intravenous immunoglobulin.

Others include medications that target mitochondrial dysfunction; ivabradine; pyridostigmine;, DRP1 inhibitors; supplements showing success in patient communities including lactoferrin, ubiquinone, and nattokinase; and therapies targeting glymphatic/lymphatic dysfunction, microbiome therapies, and therapeutic peptides. 
 

3: Use appropriate long COVID subtypes 

Long COVID is an umbrella term that encompasses multiple new-onset and worsened conditions and symptoms after COVID. Roughly half of long COVID patients likely meet the criteria for ME/CFS and/or dysautonomia. Others may have new-onset diabetes, major clotting events, lung damage, neurological disorders, loss of smell or taste, and other manifestations. 

Patients in different categories likely have different responses to treatments. It’s critical to identify appropriate subtypes for each trial, ideally performing detailed analyses to identify the treatments that work best, and don’t, for each subtype. 
 

4: Behavioral treatments, especially those that have harmed similar populations, should not be trialed

Behavioral treatments including exercise, graded exercise therapy (GET), and cognitive-behavioral therapy (CBT) should not be trialed, let alone prioritized, for long COVID. 

In patients with postexertional malaise (PEM), one of the most common long COVID symptoms, exercise is actively harmful and causes dysfunctional metabolic patterns, cardiac preload failure, impaired systemic oxygen extraction, and more. GET and CBT have failed similar populations , and exercise is explicitly contraindicated by the World Health Organization, the British National Institute for Health and Care Excellence, the CDC, and other organizations. 

Resources should instead be put toward the wide range of medications that have not yet adequately undergone clinical trials.  
 

5: PCR and antibody tests should not be used as inclusion criteria for trial participants

Only an estimated 1%-3% of cases in the first wave of COVID were documented, and the CDC estimates that only 25% of cases through September 2021 were documented. Similarly, antibody tests are unreliable to determine past infection, as roughly a third of patients don’t seroconvert, and a similar proportion serorevert within a few months. Using polymerase chain reaction (PCR) and antibody testing to determine who should be included in clinical trials limits who is eligible to participate in research, particularly those who have been ill for longer. Additionally, the majority of those who serorevert are women, so using antibody tests for inclusion introduces a selection bias and may miss mechanisms of immune system functioning that are part of long COVID.

PCR tests also have high false-negative rates and requiring them in research excludes people with lower viral loads with long COVID, which would confound findings. 

These issues with testing also lead to COVID-infected people accidentally being included in control groups, which ruins the credibility of the research findings completely.
 

6: Include comparator groups

There are several common diagnoses that occur in people with long COVID, including ME/CFS, postural orthostatic tachycardia syndrome, small-fiber neuropathy, mast cell activation syndrome, and Ehlers-Danlos syndrome.

Identifying people with these conditions within the trial cohort improves research across all fields, benefiting all groups, and helps clarify what types of patients benefit most from certain medications. 
 

7: Identify the right endpoints; avoid the wrong ones

Even though our understanding of the pathophysiology of long COVID is still evolving, it’s still possible to do clinical trials by identifying strong endpoints and outcome measures. 

Several tools have been designed for viral-onset conditions and should be used alongside other endpoints. Postexertional malaise and autonomic symptoms, which are some of the most common symptoms of long COVID, can be measured with the validated DSQ-PEM and COMPASS-31, respectively. Tools for cognitive dysfunction trials should capture specific and common types of impairment, like processing speed. 

Endpoints should be high-impact and aim for large improvements that have clinical significance over small improvements that do not have clinical significance. 

Objective tests should be incorporated where possible; some to consider include natural killer cell functioning, cerebral blood flow, T-cell functioning, levels of reactivated herpesviruses, blood lactate levels, and microclots, as testing becomes available. 

Mental health outcomes shouldn’t be primary endpoints, except where a trial is targeting a specific mental health condition because of COVID (for example, premenstrual dysphoric disorder). 

If mental health conditions are tracked secondarily, it’s vital not to use questionnaires that include physical symptoms like fatigue, difficulty concentrating, difficulty sleeping, or palpitations, as these artificially increase depression and anxiety scores in chronically ill respondents. Tools that include physical symptoms (Patient Health Questionnaire–9, Beck Anxiety Inventory, Beck Depression Inventory) can be replaced with scales like the PHQ-2, General Anxiety Disorder–7, Hospital Anxiety and Depression Scale, or PROMIS-29 subscales.

Because certain cytokines and other inflammatory markers may naturally decrease over time without corresponding improvement in the ME/CFS subtype, caution should be taken when using cytokines as endpoints.
 

8: Consider enrollment and objectives carefully

A proportion of people with long COVID will recover in the early months after infection. Ideally, clinical trials will primarily study treatments in patients who have been ill 6 months or longer, as some natural recovery will happen before that can bias studies.

But where resources are abundant, it is ideal for trials to additionally look at whether the treatments can help patients in the early months recover and prevent progression to the later stage.
 

9: Tracking illness duration is crucial

Research from ME/CFS shows that there may be an immune change in the first few years of the illness, where cytokines decrease without any corresponding change in symptom improvement. 

Because of this and the possibility that other markers follow the same pattern, disease duration should be a core feature of all analyses and trial designs. Trial outcomes should be designed to answer the question of whether the medication helps patients at different durations of illness. 
 

10: Prioritize patient populations less likely to recover without intervention

Some long COVID phenotypes seem less likely to recover without intervention. Trials should take care to focus on these patient populations, which include those with neurologic symptoms and those meeting ME/CFS criteria.

 

11: Account for the relapsing/remitting nature

Outcome measures need to be assessed in a way that can distinguish a temporary remission, which is part of the natural course of the disease, from a permanent cure. 

Factors that can contribute to the relapsing/remitting nature include physical and cognitive postexertional malaise, menstrual cycle changes, and seasonal changes.
 

12: Trial participants should reflect the diversity of the long COVID population

Certain demographics are more likely to be affected by acute and long COVID and need to be appropriately recruited and reflected in research, including in patient engagement. 

Trials must include high numbers of Hispanic/Latinx, Black, and indigenous communities, queer and transgender populations, and women. Trial materials and design need to incorporate linguistic diversity in addition to racial/ethnic diversity.

Upward of 75% of long COVID cases happen after mild acute cases; clinical researchers should ensure that nonhospitalized patients make up the bulk of trial participants. 
 

13: Utilize meaningful engagement of patients, especially in treatment selection and study design

Meaningful patient engagement means engaging multiple patients at every step of the trial process, from treatment selection to study design to analysis to communication of the results. 

Patient experiences are extremely valuable and contain information that researchers may not be familiar with, including the nature and patterns of the illness, insights into possible treatments, and barriers to documentation and care that may also impact research. Tapping into those patient experiences will make trials stronger.

Overall, the landscape of long COVID clinical trials is ripe for discovery, and researchers choosing to go down this path will be deeply appreciated by the patient community. 

Hannah Davis is a long COVID patient-researcher and cofounder of the Patient-Led Research Collaborative, an organization studying the long-term effects of COVID.

A version of this article first appeared on Medscape.com.

The Centers for Disease Control and Prevention and the U.S. Census Bureau estimate that 6.1% of the U.S. adult population is living with long COVID, with millions more debilitated worldwide. The demand for substantial treatment is enormous, but the urgency to fund and begin the necessary range of clinical trials has not met the severity of the problem.
 

While trials are slowly beginning to happen, the treatment choices and trial design require crucial nuances and understanding of viral-onset illnesses, and few research groups are creating strong trials that fully reflect the complexities of this landscape.

This article aims to share key considerations and best practices that are essential to the success of these trials. These recommendations recognize that roughly half of long COVID patients have new-onset myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia from COVID, which must be at the forefront of how trials are designed and conducted, and are additionally based on the current hypotheses about long COVID’s pathophysiologies. 
 

1: Drugs proposed by experts in postviral fields should be prioritized

Upward of 50 drugs for viral-onset conditions like ME/CFS, dysautonomia, AIDS, and others have been waiting for years to go to trial, but have not had the funding to do so. 

Treatments proposed by experts in viral-onset illnesses (such as ME/CFS and dysautonomia) should be prioritized (PM R. 2022 Oct;14[10]:1270-91), as outside researchers are not familiar with these fields and their potential treatment options.
 

2: Drugs targeting a wide range of mechanisms should be trialed

Treatments that should be trialed include anticoagulants/antiplatelets for clotting and vascular functioning, immunomodulators including JAK-STAT inhibitors, COVID-specific antivirals and antivirals against reactivated herpesviruses (Valcyte, Valacyclovir, EBV vaccine). 

Other options include prescription mast cell stabilizers (ketotifen, cromolyn sodium), drugs that regulate microglial activation (low-dose naltrexone, low-dose aripiprazole), anti-CGRP medications, beta-blockers, and intravenous immunoglobulin.

Others include medications that target mitochondrial dysfunction; ivabradine; pyridostigmine;, DRP1 inhibitors; supplements showing success in patient communities including lactoferrin, ubiquinone, and nattokinase; and therapies targeting glymphatic/lymphatic dysfunction, microbiome therapies, and therapeutic peptides. 
 

3: Use appropriate long COVID subtypes 

Long COVID is an umbrella term that encompasses multiple new-onset and worsened conditions and symptoms after COVID. Roughly half of long COVID patients likely meet the criteria for ME/CFS and/or dysautonomia. Others may have new-onset diabetes, major clotting events, lung damage, neurological disorders, loss of smell or taste, and other manifestations. 

Patients in different categories likely have different responses to treatments. It’s critical to identify appropriate subtypes for each trial, ideally performing detailed analyses to identify the treatments that work best, and don’t, for each subtype. 
 

4: Behavioral treatments, especially those that have harmed similar populations, should not be trialed

Behavioral treatments including exercise, graded exercise therapy (GET), and cognitive-behavioral therapy (CBT) should not be trialed, let alone prioritized, for long COVID. 

In patients with postexertional malaise (PEM), one of the most common long COVID symptoms, exercise is actively harmful and causes dysfunctional metabolic patterns, cardiac preload failure, impaired systemic oxygen extraction, and more. GET and CBT have failed similar populations , and exercise is explicitly contraindicated by the World Health Organization, the British National Institute for Health and Care Excellence, the CDC, and other organizations. 

Resources should instead be put toward the wide range of medications that have not yet adequately undergone clinical trials.  
 

5: PCR and antibody tests should not be used as inclusion criteria for trial participants

Only an estimated 1%-3% of cases in the first wave of COVID were documented, and the CDC estimates that only 25% of cases through September 2021 were documented. Similarly, antibody tests are unreliable to determine past infection, as roughly a third of patients don’t seroconvert, and a similar proportion serorevert within a few months. Using polymerase chain reaction (PCR) and antibody testing to determine who should be included in clinical trials limits who is eligible to participate in research, particularly those who have been ill for longer. Additionally, the majority of those who serorevert are women, so using antibody tests for inclusion introduces a selection bias and may miss mechanisms of immune system functioning that are part of long COVID.

PCR tests also have high false-negative rates and requiring them in research excludes people with lower viral loads with long COVID, which would confound findings. 

These issues with testing also lead to COVID-infected people accidentally being included in control groups, which ruins the credibility of the research findings completely.
 

6: Include comparator groups

There are several common diagnoses that occur in people with long COVID, including ME/CFS, postural orthostatic tachycardia syndrome, small-fiber neuropathy, mast cell activation syndrome, and Ehlers-Danlos syndrome.

Identifying people with these conditions within the trial cohort improves research across all fields, benefiting all groups, and helps clarify what types of patients benefit most from certain medications. 
 

7: Identify the right endpoints; avoid the wrong ones

Even though our understanding of the pathophysiology of long COVID is still evolving, it’s still possible to do clinical trials by identifying strong endpoints and outcome measures. 

Several tools have been designed for viral-onset conditions and should be used alongside other endpoints. Postexertional malaise and autonomic symptoms, which are some of the most common symptoms of long COVID, can be measured with the validated DSQ-PEM and COMPASS-31, respectively. Tools for cognitive dysfunction trials should capture specific and common types of impairment, like processing speed. 

Endpoints should be high-impact and aim for large improvements that have clinical significance over small improvements that do not have clinical significance. 

Objective tests should be incorporated where possible; some to consider include natural killer cell functioning, cerebral blood flow, T-cell functioning, levels of reactivated herpesviruses, blood lactate levels, and microclots, as testing becomes available. 

Mental health outcomes shouldn’t be primary endpoints, except where a trial is targeting a specific mental health condition because of COVID (for example, premenstrual dysphoric disorder). 

If mental health conditions are tracked secondarily, it’s vital not to use questionnaires that include physical symptoms like fatigue, difficulty concentrating, difficulty sleeping, or palpitations, as these artificially increase depression and anxiety scores in chronically ill respondents. Tools that include physical symptoms (Patient Health Questionnaire–9, Beck Anxiety Inventory, Beck Depression Inventory) can be replaced with scales like the PHQ-2, General Anxiety Disorder–7, Hospital Anxiety and Depression Scale, or PROMIS-29 subscales.

Because certain cytokines and other inflammatory markers may naturally decrease over time without corresponding improvement in the ME/CFS subtype, caution should be taken when using cytokines as endpoints.
 

8: Consider enrollment and objectives carefully

A proportion of people with long COVID will recover in the early months after infection. Ideally, clinical trials will primarily study treatments in patients who have been ill 6 months or longer, as some natural recovery will happen before that can bias studies.

But where resources are abundant, it is ideal for trials to additionally look at whether the treatments can help patients in the early months recover and prevent progression to the later stage.
 

9: Tracking illness duration is crucial

Research from ME/CFS shows that there may be an immune change in the first few years of the illness, where cytokines decrease without any corresponding change in symptom improvement. 

Because of this and the possibility that other markers follow the same pattern, disease duration should be a core feature of all analyses and trial designs. Trial outcomes should be designed to answer the question of whether the medication helps patients at different durations of illness. 
 

10: Prioritize patient populations less likely to recover without intervention

Some long COVID phenotypes seem less likely to recover without intervention. Trials should take care to focus on these patient populations, which include those with neurologic symptoms and those meeting ME/CFS criteria.

 

11: Account for the relapsing/remitting nature

Outcome measures need to be assessed in a way that can distinguish a temporary remission, which is part of the natural course of the disease, from a permanent cure. 

Factors that can contribute to the relapsing/remitting nature include physical and cognitive postexertional malaise, menstrual cycle changes, and seasonal changes.
 

12: Trial participants should reflect the diversity of the long COVID population

Certain demographics are more likely to be affected by acute and long COVID and need to be appropriately recruited and reflected in research, including in patient engagement. 

Trials must include high numbers of Hispanic/Latinx, Black, and indigenous communities, queer and transgender populations, and women. Trial materials and design need to incorporate linguistic diversity in addition to racial/ethnic diversity.

Upward of 75% of long COVID cases happen after mild acute cases; clinical researchers should ensure that nonhospitalized patients make up the bulk of trial participants. 
 

13: Utilize meaningful engagement of patients, especially in treatment selection and study design

Meaningful patient engagement means engaging multiple patients at every step of the trial process, from treatment selection to study design to analysis to communication of the results. 

Patient experiences are extremely valuable and contain information that researchers may not be familiar with, including the nature and patterns of the illness, insights into possible treatments, and barriers to documentation and care that may also impact research. Tapping into those patient experiences will make trials stronger.

Overall, the landscape of long COVID clinical trials is ripe for discovery, and researchers choosing to go down this path will be deeply appreciated by the patient community. 

Hannah Davis is a long COVID patient-researcher and cofounder of the Patient-Led Research Collaborative, an organization studying the long-term effects of COVID.

A version of this article first appeared on Medscape.com.

The Centers for Disease Control and Prevention and the U.S. Census Bureau estimate that 6.1% of the U.S. adult population is living with long COVID, with millions more debilitated worldwide. The demand for substantial treatment is enormous, but the urgency to fund and begin the necessary range of clinical trials has not met the severity of the problem.
 

While trials are slowly beginning to happen, the treatment choices and trial design require crucial nuances and understanding of viral-onset illnesses, and few research groups are creating strong trials that fully reflect the complexities of this landscape.

This article aims to share key considerations and best practices that are essential to the success of these trials. These recommendations recognize that roughly half of long COVID patients have new-onset myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia from COVID, which must be at the forefront of how trials are designed and conducted, and are additionally based on the current hypotheses about long COVID’s pathophysiologies. 
 

1: Drugs proposed by experts in postviral fields should be prioritized

Upward of 50 drugs for viral-onset conditions like ME/CFS, dysautonomia, AIDS, and others have been waiting for years to go to trial, but have not had the funding to do so. 

Treatments proposed by experts in viral-onset illnesses (such as ME/CFS and dysautonomia) should be prioritized (PM R. 2022 Oct;14[10]:1270-91), as outside researchers are not familiar with these fields and their potential treatment options.
 

2: Drugs targeting a wide range of mechanisms should be trialed

Treatments that should be trialed include anticoagulants/antiplatelets for clotting and vascular functioning, immunomodulators including JAK-STAT inhibitors, COVID-specific antivirals and antivirals against reactivated herpesviruses (Valcyte, Valacyclovir, EBV vaccine). 

Other options include prescription mast cell stabilizers (ketotifen, cromolyn sodium), drugs that regulate microglial activation (low-dose naltrexone, low-dose aripiprazole), anti-CGRP medications, beta-blockers, and intravenous immunoglobulin.

Others include medications that target mitochondrial dysfunction; ivabradine; pyridostigmine;, DRP1 inhibitors; supplements showing success in patient communities including lactoferrin, ubiquinone, and nattokinase; and therapies targeting glymphatic/lymphatic dysfunction, microbiome therapies, and therapeutic peptides. 
 

3: Use appropriate long COVID subtypes 

Long COVID is an umbrella term that encompasses multiple new-onset and worsened conditions and symptoms after COVID. Roughly half of long COVID patients likely meet the criteria for ME/CFS and/or dysautonomia. Others may have new-onset diabetes, major clotting events, lung damage, neurological disorders, loss of smell or taste, and other manifestations. 

Patients in different categories likely have different responses to treatments. It’s critical to identify appropriate subtypes for each trial, ideally performing detailed analyses to identify the treatments that work best, and don’t, for each subtype. 
 

4: Behavioral treatments, especially those that have harmed similar populations, should not be trialed

Behavioral treatments including exercise, graded exercise therapy (GET), and cognitive-behavioral therapy (CBT) should not be trialed, let alone prioritized, for long COVID. 

In patients with postexertional malaise (PEM), one of the most common long COVID symptoms, exercise is actively harmful and causes dysfunctional metabolic patterns, cardiac preload failure, impaired systemic oxygen extraction, and more. GET and CBT have failed similar populations , and exercise is explicitly contraindicated by the World Health Organization, the British National Institute for Health and Care Excellence, the CDC, and other organizations. 

Resources should instead be put toward the wide range of medications that have not yet adequately undergone clinical trials.  
 

5: PCR and antibody tests should not be used as inclusion criteria for trial participants

Only an estimated 1%-3% of cases in the first wave of COVID were documented, and the CDC estimates that only 25% of cases through September 2021 were documented. Similarly, antibody tests are unreliable to determine past infection, as roughly a third of patients don’t seroconvert, and a similar proportion serorevert within a few months. Using polymerase chain reaction (PCR) and antibody testing to determine who should be included in clinical trials limits who is eligible to participate in research, particularly those who have been ill for longer. Additionally, the majority of those who serorevert are women, so using antibody tests for inclusion introduces a selection bias and may miss mechanisms of immune system functioning that are part of long COVID.

PCR tests also have high false-negative rates and requiring them in research excludes people with lower viral loads with long COVID, which would confound findings. 

These issues with testing also lead to COVID-infected people accidentally being included in control groups, which ruins the credibility of the research findings completely.
 

6: Include comparator groups

There are several common diagnoses that occur in people with long COVID, including ME/CFS, postural orthostatic tachycardia syndrome, small-fiber neuropathy, mast cell activation syndrome, and Ehlers-Danlos syndrome.

Identifying people with these conditions within the trial cohort improves research across all fields, benefiting all groups, and helps clarify what types of patients benefit most from certain medications. 
 

7: Identify the right endpoints; avoid the wrong ones

Even though our understanding of the pathophysiology of long COVID is still evolving, it’s still possible to do clinical trials by identifying strong endpoints and outcome measures. 

Several tools have been designed for viral-onset conditions and should be used alongside other endpoints. Postexertional malaise and autonomic symptoms, which are some of the most common symptoms of long COVID, can be measured with the validated DSQ-PEM and COMPASS-31, respectively. Tools for cognitive dysfunction trials should capture specific and common types of impairment, like processing speed. 

Endpoints should be high-impact and aim for large improvements that have clinical significance over small improvements that do not have clinical significance. 

Objective tests should be incorporated where possible; some to consider include natural killer cell functioning, cerebral blood flow, T-cell functioning, levels of reactivated herpesviruses, blood lactate levels, and microclots, as testing becomes available. 

Mental health outcomes shouldn’t be primary endpoints, except where a trial is targeting a specific mental health condition because of COVID (for example, premenstrual dysphoric disorder). 

If mental health conditions are tracked secondarily, it’s vital not to use questionnaires that include physical symptoms like fatigue, difficulty concentrating, difficulty sleeping, or palpitations, as these artificially increase depression and anxiety scores in chronically ill respondents. Tools that include physical symptoms (Patient Health Questionnaire–9, Beck Anxiety Inventory, Beck Depression Inventory) can be replaced with scales like the PHQ-2, General Anxiety Disorder–7, Hospital Anxiety and Depression Scale, or PROMIS-29 subscales.

Because certain cytokines and other inflammatory markers may naturally decrease over time without corresponding improvement in the ME/CFS subtype, caution should be taken when using cytokines as endpoints.
 

8: Consider enrollment and objectives carefully

A proportion of people with long COVID will recover in the early months after infection. Ideally, clinical trials will primarily study treatments in patients who have been ill 6 months or longer, as some natural recovery will happen before that can bias studies.

But where resources are abundant, it is ideal for trials to additionally look at whether the treatments can help patients in the early months recover and prevent progression to the later stage.
 

9: Tracking illness duration is crucial

Research from ME/CFS shows that there may be an immune change in the first few years of the illness, where cytokines decrease without any corresponding change in symptom improvement. 

Because of this and the possibility that other markers follow the same pattern, disease duration should be a core feature of all analyses and trial designs. Trial outcomes should be designed to answer the question of whether the medication helps patients at different durations of illness. 
 

10: Prioritize patient populations less likely to recover without intervention

Some long COVID phenotypes seem less likely to recover without intervention. Trials should take care to focus on these patient populations, which include those with neurologic symptoms and those meeting ME/CFS criteria.

 

11: Account for the relapsing/remitting nature

Outcome measures need to be assessed in a way that can distinguish a temporary remission, which is part of the natural course of the disease, from a permanent cure. 

Factors that can contribute to the relapsing/remitting nature include physical and cognitive postexertional malaise, menstrual cycle changes, and seasonal changes.
 

12: Trial participants should reflect the diversity of the long COVID population

Certain demographics are more likely to be affected by acute and long COVID and need to be appropriately recruited and reflected in research, including in patient engagement. 

Trials must include high numbers of Hispanic/Latinx, Black, and indigenous communities, queer and transgender populations, and women. Trial materials and design need to incorporate linguistic diversity in addition to racial/ethnic diversity.

Upward of 75% of long COVID cases happen after mild acute cases; clinical researchers should ensure that nonhospitalized patients make up the bulk of trial participants. 
 

13: Utilize meaningful engagement of patients, especially in treatment selection and study design

Meaningful patient engagement means engaging multiple patients at every step of the trial process, from treatment selection to study design to analysis to communication of the results. 

Patient experiences are extremely valuable and contain information that researchers may not be familiar with, including the nature and patterns of the illness, insights into possible treatments, and barriers to documentation and care that may also impact research. Tapping into those patient experiences will make trials stronger.

Overall, the landscape of long COVID clinical trials is ripe for discovery, and researchers choosing to go down this path will be deeply appreciated by the patient community. 

Hannah Davis is a long COVID patient-researcher and cofounder of the Patient-Led Research Collaborative, an organization studying the long-term effects of COVID.

A version of this article first appeared on Medscape.com.

The inappropriate use of antibiotics is associated with an increased risk of antibiotic resistance, health care costs, and risk of adverse drug reactions.¹ According to the Centers for Disease Control and Prevention (CDC), a 10% decrease in overall antibiotic use across different wards was associated with a 34% decrease in Clostridioides difficile (C difficile) infections.² In addition, antimicrobial resistance accounts for > 2.8 million infections and > 35,000 deaths each year.³ The estimated total economic costs of antibiotic resistance to the US economy have ranged as high as $20 billion in excess direct health care costs.⁴ A main goal of an antimicrobial stewardship program (ASP) is to optimize antibiotic use to prevent the adverse consequences of inappropriate antibiotic prescribing.

During the COVID-19 pandemic, increased use of empiric antibiotic therapy has been observed. According to the CDC, almost 80% of patients hospitalized with COVID-19 received an antibiotic from March 2020 to October 2020.⁵ Studies were conducted to investigate the prevalence of bacterial coinfection in patients with COVID-19 and whether antibiotics were indicated in this patient population. A United Kingdom multicenter, prospective cohort study showed a high proportion of patients hospitalized with COVID-19 received antimicrobials despite microbiologically confirmed bacterial infections being rare and more likely to be secondary infections.⁶

Many other studies have reported similar findings. Langord and colleagues found the prevalence of bacterial coinfection in patients with COVID-19 was 3.5% but that 71.9% received antibiotics.⁷ Coenen and colleagues identified 12.4% of the patients with possible and 1.1% of patients with probable bacterial coinfection, while 81% of the study population and 78% of patients were classified as unlikely bacterial coinfection received antibiotics.⁸

At Veterans Affairs Southern Nevada Healthcare System (VASNHS), an ASP team consisting of an infectious disease (ID) physician and 2 pharmacists provide daily prospective audits with intervention and feedback along with other interventions, such as providing restricted order menus, institutional treatment guidelines, and staff education to help improve antibiotic prescribing. The ASP pharmacists have a scope of practice to make changes to anti-infective therapies. The purpose of this study was to describe antibiotic prescribing in patients hospitalized with COVID-19 from November 1, 2020, to January 31, 2021, in an ASP setting led by pharmacists.

Methods

This retrospective descriptive study included patients who were hospitalized for the treatment of laboratory-confirmed COVID-19 infection. The Theradoc clinical surveillance system was used to retrieve a list of patients who were admitted to VASNHS from November 1, 2020, to January 31, 2021, and tested positive for COVID-19. Patients with incidental positive COVID-19 test results or those who received antibiotics for extrapulmonary indications on hospital admission were excluded.

Each patient chart was reviewed and data, including clinical presentations, procalcitonin (PCT), the requirement of supplemental oxygen, vital signs, imaging findings, antibiotic orders on admission, ASP interventions such as discontinuation or changes to antibiotic therapy during the first 72 hours of hospital admission, clinical outcomes, culture results, and readmission rate, defined as any hospital admission related to COVID-19 or respiratory tract infection within 30 days from the previous discharge, were collected.

The primary objective of the study was to describe antibiotic prescribing in patients hospitalized with COVID-19. The secondary outcomes included the prevalence of bacterial coinfection and nosocomial bacterial infection in patients hospitalized with COVID-19.

Results

A total of 199 patients were admitted to the hospital for laboratory-confirmed COVID-19 infection from November 1, 2020, to January 31, 2021. Sixty-one patients (31%) received at least 1 antibiotic on hospital admission. Among those patients who received empiric antibiotic treatment, 29 patients (48%) met the Systemic Inflammatory Response Syndrome (SIRS) criteria. Fifty-six patients (92%) had ≥ 1 PCT level obtained, and 26 of those (46%) presented with elevated PCT levels (PCT > 0.25). Fifty patients (82%) required oxygen supplement and 49 (80%) presented with remarkable imaging findings. Of 138 patients who did not receive empiric antibiotic therapy within 72 hours of hospital admission, 56 (41%) met the SIRS criteria, 31 (29%) had elevated PCT levels, 100 (72%) required oxygen supplement, and 79 (59%) presented with remarkable imaging findings.

Antibiotic Prescribing

Forty-six of 61 patients (75%) received antibiotic treatment for community-acquired pneumonia (CAP) that included ceftriaxone and azithromycin. Three patients (5%) received ≥ 1 broad-spectrum antibiotic (4th generation cephalosporin [cefepime] or piperacillin-tazobactam), 2 (3%) received vancomycin, and 1 (2%) received a fluoroquinolone (levofloxacin) on admission.

Among 61 patients who received empiric antibiotics, the readmission rate was 6%. The mortality rate was 20%, and the mean (SD) duration of hospital stay was 13.1 (12.5) days. There were 47 patients (77%) who had antibiotics discontinued by the ASP within 72 hours of admission. Among these patients, the readmission rate was 8% and the mortality rate was 15%. The mean (SD) duration of hospital stay was 12.7 (13.3) days. In the group of patients without empiric antibiotic therapy, the readmission rate was 6%, the mortality rate was 10%, and the mean (SD) duration of hospital stay was 10.1 (9.5) days.

Six of 199 patients (3%) had microbiologically confirmed bacterial coinfection on hospital admission: 3 were Pseudomonas aeruginosa (P aeruginosa) and 2 were Klebsiella oxytoca (Table 1).

Discussion

Prospective audit and feedback and preauthorization are recommended in guidelines as “core components of any stewardship program.”⁹ At VASNHS, the ASP performs daily prospective audits with intervention and feedback. Efforts have been made to maintain daily ASP activities during the pandemic. This study aimed to describe antibiotic prescribing for patients hospitalized with COVID-19 in a pharmacist-led ASP setting. It was found that up to 31% of the patients received ≥ 1 antibiotic on admission for empiric treatment of bacterial coinfection. About half of these patients met the SIRS criteria. Most of these patients received ceftriaxone and azithromycin for concern of CAP. ASP discontinued antibiotics within 72 hours in most of the patients. Chart review and discussion with ID physicians and/or hospitalists determined the probability of bacterial coinfection as well as any potential complication or patient-specific risk factor. It is important to note that most patients who received antibiotics on admission had ≥ 1 PCT level and up to 46% of them had a PCT level > 0.25. However, according to Relph and colleagues, PCT may not be a reliable indicator of bacterial infection in severe viral diseases with raised interleukin-6 levels.¹⁰ An elevated PCT level should not be the sole indicator for empiric antibiotic treatment.

Study findings confirmed the low prevalence of bacterial coinfection in patients hospitalized with COVID-19. The overuse of empiric antibiotics in a patient population unlikely to present with bacterial coinfection is concerning. It is essential to continue promoting antimicrobial stewardship during the COVID-19 pandemic to ensure appropriate and responsible antimicrobial prescribing. A thorough clinical assessment consisting of comorbidities, clinical symptoms, radiologic and microbiologic findings, as well as other relevant workup or biomarker results is crucial to determine whether the antibiotic is strongly indicated in patients hospitalized with COVID-19. Empiric antibiotic therapy should be considered only in patients with clinical findings suggestive of bacterial coinfection.

Limitations

Limitations of our study included the study design (single-center, retrospective review, lack of comparative group) and small sample size with a 3-month study period. In addition, respiratory cultures are not commonly obtained in patients who present with mild-to-moderate CAP. Using culture results solely to confirm bacterial coinfection in patients with COVID-19 could have underestimated the prevalence of bacterial infection. Developing diagnostic criteria that include clinical signs and symptoms, imaging findings, and laboratory results as well as culture results would help to better assess the presence of bacterial coinfection in this patient population.

Conclusions

The study findings showed that up to 30% of patients hospitalized for COVID-19 infection received empiric antibiotic treatment for concern of bacterial coinfection. A pharmacist-led ASP provided interventions, including early discontinuation of antibiotics in 77% of these patients.

A low prevalence of bacterial coinfection (3%) in patients hospitalized with COVID-19 also was reported. A thorough clinical workup to determine the risk of bacterial coinfection in patients with COVID-19 is important before starting empiric antibiotic therapy. Continuing to promote the ASP during the COVID-19 pandemic to ensure responsible antibiotic use and prevent antimicrobial resistance is essential.

The inappropriate use of antibiotics is associated with an increased risk of antibiotic resistance, health care costs, and risk of adverse drug reactions.¹ According to the Centers for Disease Control and Prevention (CDC), a 10% decrease in overall antibiotic use across different wards was associated with a 34% decrease in Clostridioides difficile (C difficile) infections.² In addition, antimicrobial resistance accounts for > 2.8 million infections and > 35,000 deaths each year.³ The estimated total economic costs of antibiotic resistance to the US economy have ranged as high as $20 billion in excess direct health care costs.⁴ A main goal of an antimicrobial stewardship program (ASP) is to optimize antibiotic use to prevent the adverse consequences of inappropriate antibiotic prescribing.

During the COVID-19 pandemic, increased use of empiric antibiotic therapy has been observed. According to the CDC, almost 80% of patients hospitalized with COVID-19 received an antibiotic from March 2020 to October 2020.⁵ Studies were conducted to investigate the prevalence of bacterial coinfection in patients with COVID-19 and whether antibiotics were indicated in this patient population. A United Kingdom multicenter, prospective cohort study showed a high proportion of patients hospitalized with COVID-19 received antimicrobials despite microbiologically confirmed bacterial infections being rare and more likely to be secondary infections.⁶

Many other studies have reported similar findings. Langord and colleagues found the prevalence of bacterial coinfection in patients with COVID-19 was 3.5% but that 71.9% received antibiotics.⁷ Coenen and colleagues identified 12.4% of the patients with possible and 1.1% of patients with probable bacterial coinfection, while 81% of the study population and 78% of patients were classified as unlikely bacterial coinfection received antibiotics.⁸

At Veterans Affairs Southern Nevada Healthcare System (VASNHS), an ASP team consisting of an infectious disease (ID) physician and 2 pharmacists provide daily prospective audits with intervention and feedback along with other interventions, such as providing restricted order menus, institutional treatment guidelines, and staff education to help improve antibiotic prescribing. The ASP pharmacists have a scope of practice to make changes to anti-infective therapies. The purpose of this study was to describe antibiotic prescribing in patients hospitalized with COVID-19 from November 1, 2020, to January 31, 2021, in an ASP setting led by pharmacists.

Methods

This retrospective descriptive study included patients who were hospitalized for the treatment of laboratory-confirmed COVID-19 infection. The Theradoc clinical surveillance system was used to retrieve a list of patients who were admitted to VASNHS from November 1, 2020, to January 31, 2021, and tested positive for COVID-19. Patients with incidental positive COVID-19 test results or those who received antibiotics for extrapulmonary indications on hospital admission were excluded.

Each patient chart was reviewed and data, including clinical presentations, procalcitonin (PCT), the requirement of supplemental oxygen, vital signs, imaging findings, antibiotic orders on admission, ASP interventions such as discontinuation or changes to antibiotic therapy during the first 72 hours of hospital admission, clinical outcomes, culture results, and readmission rate, defined as any hospital admission related to COVID-19 or respiratory tract infection within 30 days from the previous discharge, were collected.

The primary objective of the study was to describe antibiotic prescribing in patients hospitalized with COVID-19. The secondary outcomes included the prevalence of bacterial coinfection and nosocomial bacterial infection in patients hospitalized with COVID-19.

Results

A total of 199 patients were admitted to the hospital for laboratory-confirmed COVID-19 infection from November 1, 2020, to January 31, 2021. Sixty-one patients (31%) received at least 1 antibiotic on hospital admission. Among those patients who received empiric antibiotic treatment, 29 patients (48%) met the Systemic Inflammatory Response Syndrome (SIRS) criteria. Fifty-six patients (92%) had ≥ 1 PCT level obtained, and 26 of those (46%) presented with elevated PCT levels (PCT > 0.25). Fifty patients (82%) required oxygen supplement and 49 (80%) presented with remarkable imaging findings. Of 138 patients who did not receive empiric antibiotic therapy within 72 hours of hospital admission, 56 (41%) met the SIRS criteria, 31 (29%) had elevated PCT levels, 100 (72%) required oxygen supplement, and 79 (59%) presented with remarkable imaging findings.

Antibiotic Prescribing

Forty-six of 61 patients (75%) received antibiotic treatment for community-acquired pneumonia (CAP) that included ceftriaxone and azithromycin. Three patients (5%) received ≥ 1 broad-spectrum antibiotic (4th generation cephalosporin [cefepime] or piperacillin-tazobactam), 2 (3%) received vancomycin, and 1 (2%) received a fluoroquinolone (levofloxacin) on admission.

Among 61 patients who received empiric antibiotics, the readmission rate was 6%. The mortality rate was 20%, and the mean (SD) duration of hospital stay was 13.1 (12.5) days. There were 47 patients (77%) who had antibiotics discontinued by the ASP within 72 hours of admission. Among these patients, the readmission rate was 8% and the mortality rate was 15%. The mean (SD) duration of hospital stay was 12.7 (13.3) days. In the group of patients without empiric antibiotic therapy, the readmission rate was 6%, the mortality rate was 10%, and the mean (SD) duration of hospital stay was 10.1 (9.5) days.

Six of 199 patients (3%) had microbiologically confirmed bacterial coinfection on hospital admission: 3 were Pseudomonas aeruginosa (P aeruginosa) and 2 were Klebsiella oxytoca (Table 1).

Discussion

Prospective audit and feedback and preauthorization are recommended in guidelines as “core components of any stewardship program.”⁹ At VASNHS, the ASP performs daily prospective audits with intervention and feedback. Efforts have been made to maintain daily ASP activities during the pandemic. This study aimed to describe antibiotic prescribing for patients hospitalized with COVID-19 in a pharmacist-led ASP setting. It was found that up to 31% of the patients received ≥ 1 antibiotic on admission for empiric treatment of bacterial coinfection. About half of these patients met the SIRS criteria. Most of these patients received ceftriaxone and azithromycin for concern of CAP. ASP discontinued antibiotics within 72 hours in most of the patients. Chart review and discussion with ID physicians and/or hospitalists determined the probability of bacterial coinfection as well as any potential complication or patient-specific risk factor. It is important to note that most patients who received antibiotics on admission had ≥ 1 PCT level and up to 46% of them had a PCT level > 0.25. However, according to Relph and colleagues, PCT may not be a reliable indicator of bacterial infection in severe viral diseases with raised interleukin-6 levels.¹⁰ An elevated PCT level should not be the sole indicator for empiric antibiotic treatment.

Study findings confirmed the low prevalence of bacterial coinfection in patients hospitalized with COVID-19. The overuse of empiric antibiotics in a patient population unlikely to present with bacterial coinfection is concerning. It is essential to continue promoting antimicrobial stewardship during the COVID-19 pandemic to ensure appropriate and responsible antimicrobial prescribing. A thorough clinical assessment consisting of comorbidities, clinical symptoms, radiologic and microbiologic findings, as well as other relevant workup or biomarker results is crucial to determine whether the antibiotic is strongly indicated in patients hospitalized with COVID-19. Empiric antibiotic therapy should be considered only in patients with clinical findings suggestive of bacterial coinfection.

Limitations

Limitations of our study included the study design (single-center, retrospective review, lack of comparative group) and small sample size with a 3-month study period. In addition, respiratory cultures are not commonly obtained in patients who present with mild-to-moderate CAP. Using culture results solely to confirm bacterial coinfection in patients with COVID-19 could have underestimated the prevalence of bacterial infection. Developing diagnostic criteria that include clinical signs and symptoms, imaging findings, and laboratory results as well as culture results would help to better assess the presence of bacterial coinfection in this patient population.

Conclusions

The study findings showed that up to 30% of patients hospitalized for COVID-19 infection received empiric antibiotic treatment for concern of bacterial coinfection. A pharmacist-led ASP provided interventions, including early discontinuation of antibiotics in 77% of these patients.

A low prevalence of bacterial coinfection (3%) in patients hospitalized with COVID-19 also was reported. A thorough clinical workup to determine the risk of bacterial coinfection in patients with COVID-19 is important before starting empiric antibiotic therapy. Continuing to promote the ASP during the COVID-19 pandemic to ensure responsible antibiotic use and prevent antimicrobial resistance is essential.

The inappropriate use of antibiotics is associated with an increased risk of antibiotic resistance, health care costs, and risk of adverse drug reactions.¹ According to the Centers for Disease Control and Prevention (CDC), a 10% decrease in overall antibiotic use across different wards was associated with a 34% decrease in Clostridioides difficile (C difficile) infections.² In addition, antimicrobial resistance accounts for > 2.8 million infections and > 35,000 deaths each year.³ The estimated total economic costs of antibiotic resistance to the US economy have ranged as high as $20 billion in excess direct health care costs.⁴ A main goal of an antimicrobial stewardship program (ASP) is to optimize antibiotic use to prevent the adverse consequences of inappropriate antibiotic prescribing.

During the COVID-19 pandemic, increased use of empiric antibiotic therapy has been observed. According to the CDC, almost 80% of patients hospitalized with COVID-19 received an antibiotic from March 2020 to October 2020.⁵ Studies were conducted to investigate the prevalence of bacterial coinfection in patients with COVID-19 and whether antibiotics were indicated in this patient population. A United Kingdom multicenter, prospective cohort study showed a high proportion of patients hospitalized with COVID-19 received antimicrobials despite microbiologically confirmed bacterial infections being rare and more likely to be secondary infections.⁶

Many other studies have reported similar findings. Langord and colleagues found the prevalence of bacterial coinfection in patients with COVID-19 was 3.5% but that 71.9% received antibiotics.⁷ Coenen and colleagues identified 12.4% of the patients with possible and 1.1% of patients with probable bacterial coinfection, while 81% of the study population and 78% of patients were classified as unlikely bacterial coinfection received antibiotics.⁸

At Veterans Affairs Southern Nevada Healthcare System (VASNHS), an ASP team consisting of an infectious disease (ID) physician and 2 pharmacists provide daily prospective audits with intervention and feedback along with other interventions, such as providing restricted order menus, institutional treatment guidelines, and staff education to help improve antibiotic prescribing. The ASP pharmacists have a scope of practice to make changes to anti-infective therapies. The purpose of this study was to describe antibiotic prescribing in patients hospitalized with COVID-19 from November 1, 2020, to January 31, 2021, in an ASP setting led by pharmacists.

Methods

This retrospective descriptive study included patients who were hospitalized for the treatment of laboratory-confirmed COVID-19 infection. The Theradoc clinical surveillance system was used to retrieve a list of patients who were admitted to VASNHS from November 1, 2020, to January 31, 2021, and tested positive for COVID-19. Patients with incidental positive COVID-19 test results or those who received antibiotics for extrapulmonary indications on hospital admission were excluded.

Each patient chart was reviewed and data, including clinical presentations, procalcitonin (PCT), the requirement of supplemental oxygen, vital signs, imaging findings, antibiotic orders on admission, ASP interventions such as discontinuation or changes to antibiotic therapy during the first 72 hours of hospital admission, clinical outcomes, culture results, and readmission rate, defined as any hospital admission related to COVID-19 or respiratory tract infection within 30 days from the previous discharge, were collected.

The primary objective of the study was to describe antibiotic prescribing in patients hospitalized with COVID-19. The secondary outcomes included the prevalence of bacterial coinfection and nosocomial bacterial infection in patients hospitalized with COVID-19.

Results

A total of 199 patients were admitted to the hospital for laboratory-confirmed COVID-19 infection from November 1, 2020, to January 31, 2021. Sixty-one patients (31%) received at least 1 antibiotic on hospital admission. Among those patients who received empiric antibiotic treatment, 29 patients (48%) met the Systemic Inflammatory Response Syndrome (SIRS) criteria. Fifty-six patients (92%) had ≥ 1 PCT level obtained, and 26 of those (46%) presented with elevated PCT levels (PCT > 0.25). Fifty patients (82%) required oxygen supplement and 49 (80%) presented with remarkable imaging findings. Of 138 patients who did not receive empiric antibiotic therapy within 72 hours of hospital admission, 56 (41%) met the SIRS criteria, 31 (29%) had elevated PCT levels, 100 (72%) required oxygen supplement, and 79 (59%) presented with remarkable imaging findings.

Antibiotic Prescribing

Forty-six of 61 patients (75%) received antibiotic treatment for community-acquired pneumonia (CAP) that included ceftriaxone and azithromycin. Three patients (5%) received ≥ 1 broad-spectrum antibiotic (4th generation cephalosporin [cefepime] or piperacillin-tazobactam), 2 (3%) received vancomycin, and 1 (2%) received a fluoroquinolone (levofloxacin) on admission.

Among 61 patients who received empiric antibiotics, the readmission rate was 6%. The mortality rate was 20%, and the mean (SD) duration of hospital stay was 13.1 (12.5) days. There were 47 patients (77%) who had antibiotics discontinued by the ASP within 72 hours of admission. Among these patients, the readmission rate was 8% and the mortality rate was 15%. The mean (SD) duration of hospital stay was 12.7 (13.3) days. In the group of patients without empiric antibiotic therapy, the readmission rate was 6%, the mortality rate was 10%, and the mean (SD) duration of hospital stay was 10.1 (9.5) days.

Six of 199 patients (3%) had microbiologically confirmed bacterial coinfection on hospital admission: 3 were Pseudomonas aeruginosa (P aeruginosa) and 2 were Klebsiella oxytoca (Table 1).

Discussion

Prospective audit and feedback and preauthorization are recommended in guidelines as “core components of any stewardship program.”⁹ At VASNHS, the ASP performs daily prospective audits with intervention and feedback. Efforts have been made to maintain daily ASP activities during the pandemic. This study aimed to describe antibiotic prescribing for patients hospitalized with COVID-19 in a pharmacist-led ASP setting. It was found that up to 31% of the patients received ≥ 1 antibiotic on admission for empiric treatment of bacterial coinfection. About half of these patients met the SIRS criteria. Most of these patients received ceftriaxone and azithromycin for concern of CAP. ASP discontinued antibiotics within 72 hours in most of the patients. Chart review and discussion with ID physicians and/or hospitalists determined the probability of bacterial coinfection as well as any potential complication or patient-specific risk factor. It is important to note that most patients who received antibiotics on admission had ≥ 1 PCT level and up to 46% of them had a PCT level > 0.25. However, according to Relph and colleagues, PCT may not be a reliable indicator of bacterial infection in severe viral diseases with raised interleukin-6 levels.¹⁰ An elevated PCT level should not be the sole indicator for empiric antibiotic treatment.

Study findings confirmed the low prevalence of bacterial coinfection in patients hospitalized with COVID-19. The overuse of empiric antibiotics in a patient population unlikely to present with bacterial coinfection is concerning. It is essential to continue promoting antimicrobial stewardship during the COVID-19 pandemic to ensure appropriate and responsible antimicrobial prescribing. A thorough clinical assessment consisting of comorbidities, clinical symptoms, radiologic and microbiologic findings, as well as other relevant workup or biomarker results is crucial to determine whether the antibiotic is strongly indicated in patients hospitalized with COVID-19. Empiric antibiotic therapy should be considered only in patients with clinical findings suggestive of bacterial coinfection.

Limitations

Limitations of our study included the study design (single-center, retrospective review, lack of comparative group) and small sample size with a 3-month study period. In addition, respiratory cultures are not commonly obtained in patients who present with mild-to-moderate CAP. Using culture results solely to confirm bacterial coinfection in patients with COVID-19 could have underestimated the prevalence of bacterial infection. Developing diagnostic criteria that include clinical signs and symptoms, imaging findings, and laboratory results as well as culture results would help to better assess the presence of bacterial coinfection in this patient population.

Conclusions

The study findings showed that up to 30% of patients hospitalized for COVID-19 infection received empiric antibiotic treatment for concern of bacterial coinfection. A pharmacist-led ASP provided interventions, including early discontinuation of antibiotics in 77% of these patients.

A low prevalence of bacterial coinfection (3%) in patients hospitalized with COVID-19 also was reported. A thorough clinical workup to determine the risk of bacterial coinfection in patients with COVID-19 is important before starting empiric antibiotic therapy. Continuing to promote the ASP during the COVID-19 pandemic to ensure responsible antibiotic use and prevent antimicrobial resistance is essential.

A cohort study of more than 1.5 million hospital admissions in Canada through the first 2 years of the COVID-19 pandemic has quantified the benefit of vaccinations. Unvaccinated patients were found to be up to 15 times more likely to die from COVID-19 than fully vaccinated patients.

Investigators analyzed 1.513 million admissions at 155 hospitals across Canada from March 15, 2020, to May 28, 2022. The study included 51,679 adult admissions and 4,035 pediatric admissions for COVID-19. Although the share of COVID-19 admissions increased in the fifth and sixth waves, from Dec. 26, 2021, to March 19, 2022 – after the full vaccine rollout – to 7.73% from 2.47% in the previous four waves, the proportion of adults admitted to the intensive care unit was significantly lower, at 8.7% versus 21.8% (odds ratio, 0.35; 95% confidence interval, 0.32-0.36).

“The good thing about waves five and six was we were able to show the COVID cases tended to be less severe, but on the other hand, because the disease in the community was so much higher, the demands on the health care system were much higher than the previous waves,” study author Charles Frenette, MD, director of infection prevention and control at McGill University, Montreal, and chair of the study’s adult subgroup, said in an interview. “But here we were able to show the benefit of vaccinations, particularly the boosting dose, in protecting against those severe outcomes.”

The study, published  in JAMA Network Open, used the Canadian Nosocomial Infection Surveillance Program database, which collects hospital data across Canada. It was activated in March 2020 to collect details on all COVID-19 admissions, co-author Nisha Thampi, MD, chair of the study’s pediatric subgroup, told this news organization.

“We’re now over 3 years into the pandemic, and CNISP continues to monitor COVID-19 as well as other pathogens in near real time,” said Dr. Thampi, an associate professor and infectious disease specialist at Children’s Hospital of Eastern Ontario.

“That’s a particular strength of this surveillance program as well. We would see this data on a biweekly basis, and that allows for [us] to implement timely protection and action.”
 

Tracing trends over six waves

The study tracked COVID-19 hospitalizations during six waves. The first lasted from March 15 to August 31, 2020, and the second lasted from Sept. 1, 2020, to Feb. 28, 2021. The wild-type variant was dominant during both waves. The third wave lasted from March 1 to June 30, 2021, and was marked by the mixed Alpha, Beta, and Gamma variants. The fourth wave lasted from July 1 to Dec. 25, 2021, when the Alpha variant was dominant. The Omicron variant dominated during waves five (Dec. 26, 2021, to March 19, 2022) and six (March 20 to May 28, 2022).

Hospitalizations reached a peak of 14,461 in wave five. ICU admissions, however, peaked at 2,164 during wave four, and all-cause deaths peaked at 1,663 during wave two.

The investigators also analyzed how unvaccinated patients fared, compared with the fully vaccinated and the fully vaccinated-plus (that is, patients with one or more additional doses). During waves five and six, unvaccinated patients were 4.3 times more likely to end up in the ICU than fully vaccinated patients and were 12.2 times more likely than fully vaccinated-plus patients. Likewise, the rate for all-cause in-hospital death for unvaccinated patients was 3.9 times greater than that for fully vaccinated patients and 15.1 times greater than that for fully vaccinated-plus patients.

The effect of vaccines emerged in waves three and four, said Dr. Frenette. “We started to see really, really significant protection and benefit from the vaccine, not only in incidence of admission but also in the incidence of complications of ICU care, ventilation, and mortality.”

Results for pediatric patients were similar to those for adults, Dr. Thampi noted. During waves five and six, overall admissions peaked, but the share of ICU admissions decreased to 9.4% from 18.1%, which was the rate during the previous four waves (OR, 0.47).

“What’s important is how pediatric hospitalizations changed over the course of the various waves,” said Dr. Thampi.

“Where we saw the highest admissions during the early Omicron dominance, we actually had the lowest numbers of hospitalizations with death and admissions into ICUs.”
 

Doing more with the data

David Fisman, MD, MPH, a professor of epidemiology at the University of Toronto, said, “This is a study that shows us how tremendously dramatic the effects of the COVID-19 vaccine were in terms of saving lives during the pandemic.” Dr. Fisman was not involved in the study.

But CNISP, which receives funding from Public Health Agency of Canada, could do more with the data it collects to better protect the public from COVID-19 and other nosocomial infections, Dr. Fisman said.

“The first problematic thing about this paper is that Canadians are paying for a surveillance system that looks at risks of acquiring infections, including COVID-19 infections, in the hospital, but that data is not fed back to the people paying for its production,” he said.

“So, Canadians don’t have the ability to really understand in real time how much risk they’re experiencing via going to the hospital for some other reason.”

The study was independently supported. Dr. Frenette and Dr. Thampi report no relevant financial relationships. Dr. Fisman has disclosed financial relationships with Pfizer, AstraZeneca, Sanofi, Seqirus, Merck, the Ontario Nurses Association, and the Elementary Teachers’ Federation of Ontario.

A version of this article first appeared on Medscape.com.

A cohort study of more than 1.5 million hospital admissions in Canada through the first 2 years of the COVID-19 pandemic has quantified the benefit of vaccinations. Unvaccinated patients were found to be up to 15 times more likely to die from COVID-19 than fully vaccinated patients.

Investigators analyzed 1.513 million admissions at 155 hospitals across Canada from March 15, 2020, to May 28, 2022. The study included 51,679 adult admissions and 4,035 pediatric admissions for COVID-19. Although the share of COVID-19 admissions increased in the fifth and sixth waves, from Dec. 26, 2021, to March 19, 2022 – after the full vaccine rollout – to 7.73% from 2.47% in the previous four waves, the proportion of adults admitted to the intensive care unit was significantly lower, at 8.7% versus 21.8% (odds ratio, 0.35; 95% confidence interval, 0.32-0.36).

“The good thing about waves five and six was we were able to show the COVID cases tended to be less severe, but on the other hand, because the disease in the community was so much higher, the demands on the health care system were much higher than the previous waves,” study author Charles Frenette, MD, director of infection prevention and control at McGill University, Montreal, and chair of the study’s adult subgroup, said in an interview. “But here we were able to show the benefit of vaccinations, particularly the boosting dose, in protecting against those severe outcomes.”

The study, published  in JAMA Network Open, used the Canadian Nosocomial Infection Surveillance Program database, which collects hospital data across Canada. It was activated in March 2020 to collect details on all COVID-19 admissions, co-author Nisha Thampi, MD, chair of the study’s pediatric subgroup, told this news organization.

“We’re now over 3 years into the pandemic, and CNISP continues to monitor COVID-19 as well as other pathogens in near real time,” said Dr. Thampi, an associate professor and infectious disease specialist at Children’s Hospital of Eastern Ontario.

“That’s a particular strength of this surveillance program as well. We would see this data on a biweekly basis, and that allows for [us] to implement timely protection and action.”
 

Tracing trends over six waves

The study tracked COVID-19 hospitalizations during six waves. The first lasted from March 15 to August 31, 2020, and the second lasted from Sept. 1, 2020, to Feb. 28, 2021. The wild-type variant was dominant during both waves. The third wave lasted from March 1 to June 30, 2021, and was marked by the mixed Alpha, Beta, and Gamma variants. The fourth wave lasted from July 1 to Dec. 25, 2021, when the Alpha variant was dominant. The Omicron variant dominated during waves five (Dec. 26, 2021, to March 19, 2022) and six (March 20 to May 28, 2022).

Hospitalizations reached a peak of 14,461 in wave five. ICU admissions, however, peaked at 2,164 during wave four, and all-cause deaths peaked at 1,663 during wave two.

The investigators also analyzed how unvaccinated patients fared, compared with the fully vaccinated and the fully vaccinated-plus (that is, patients with one or more additional doses). During waves five and six, unvaccinated patients were 4.3 times more likely to end up in the ICU than fully vaccinated patients and were 12.2 times more likely than fully vaccinated-plus patients. Likewise, the rate for all-cause in-hospital death for unvaccinated patients was 3.9 times greater than that for fully vaccinated patients and 15.1 times greater than that for fully vaccinated-plus patients.

The effect of vaccines emerged in waves three and four, said Dr. Frenette. “We started to see really, really significant protection and benefit from the vaccine, not only in incidence of admission but also in the incidence of complications of ICU care, ventilation, and mortality.”

Results for pediatric patients were similar to those for adults, Dr. Thampi noted. During waves five and six, overall admissions peaked, but the share of ICU admissions decreased to 9.4% from 18.1%, which was the rate during the previous four waves (OR, 0.47).

“What’s important is how pediatric hospitalizations changed over the course of the various waves,” said Dr. Thampi.

“Where we saw the highest admissions during the early Omicron dominance, we actually had the lowest numbers of hospitalizations with death and admissions into ICUs.”
 

Doing more with the data

David Fisman, MD, MPH, a professor of epidemiology at the University of Toronto, said, “This is a study that shows us how tremendously dramatic the effects of the COVID-19 vaccine were in terms of saving lives during the pandemic.” Dr. Fisman was not involved in the study.

But CNISP, which receives funding from Public Health Agency of Canada, could do more with the data it collects to better protect the public from COVID-19 and other nosocomial infections, Dr. Fisman said.

“The first problematic thing about this paper is that Canadians are paying for a surveillance system that looks at risks of acquiring infections, including COVID-19 infections, in the hospital, but that data is not fed back to the people paying for its production,” he said.

“So, Canadians don’t have the ability to really understand in real time how much risk they’re experiencing via going to the hospital for some other reason.”

The study was independently supported. Dr. Frenette and Dr. Thampi report no relevant financial relationships. Dr. Fisman has disclosed financial relationships with Pfizer, AstraZeneca, Sanofi, Seqirus, Merck, the Ontario Nurses Association, and the Elementary Teachers’ Federation of Ontario.

A version of this article first appeared on Medscape.com.

A cohort study of more than 1.5 million hospital admissions in Canada through the first 2 years of the COVID-19 pandemic has quantified the benefit of vaccinations. Unvaccinated patients were found to be up to 15 times more likely to die from COVID-19 than fully vaccinated patients.

Investigators analyzed 1.513 million admissions at 155 hospitals across Canada from March 15, 2020, to May 28, 2022. The study included 51,679 adult admissions and 4,035 pediatric admissions for COVID-19. Although the share of COVID-19 admissions increased in the fifth and sixth waves, from Dec. 26, 2021, to March 19, 2022 – after the full vaccine rollout – to 7.73% from 2.47% in the previous four waves, the proportion of adults admitted to the intensive care unit was significantly lower, at 8.7% versus 21.8% (odds ratio, 0.35; 95% confidence interval, 0.32-0.36).

“The good thing about waves five and six was we were able to show the COVID cases tended to be less severe, but on the other hand, because the disease in the community was so much higher, the demands on the health care system were much higher than the previous waves,” study author Charles Frenette, MD, director of infection prevention and control at McGill University, Montreal, and chair of the study’s adult subgroup, said in an interview. “But here we were able to show the benefit of vaccinations, particularly the boosting dose, in protecting against those severe outcomes.”

The study, published  in JAMA Network Open, used the Canadian Nosocomial Infection Surveillance Program database, which collects hospital data across Canada. It was activated in March 2020 to collect details on all COVID-19 admissions, co-author Nisha Thampi, MD, chair of the study’s pediatric subgroup, told this news organization.

“We’re now over 3 years into the pandemic, and CNISP continues to monitor COVID-19 as well as other pathogens in near real time,” said Dr. Thampi, an associate professor and infectious disease specialist at Children’s Hospital of Eastern Ontario.

“That’s a particular strength of this surveillance program as well. We would see this data on a biweekly basis, and that allows for [us] to implement timely protection and action.”
 

Tracing trends over six waves

The study tracked COVID-19 hospitalizations during six waves. The first lasted from March 15 to August 31, 2020, and the second lasted from Sept. 1, 2020, to Feb. 28, 2021. The wild-type variant was dominant during both waves. The third wave lasted from March 1 to June 30, 2021, and was marked by the mixed Alpha, Beta, and Gamma variants. The fourth wave lasted from July 1 to Dec. 25, 2021, when the Alpha variant was dominant. The Omicron variant dominated during waves five (Dec. 26, 2021, to March 19, 2022) and six (March 20 to May 28, 2022).

Hospitalizations reached a peak of 14,461 in wave five. ICU admissions, however, peaked at 2,164 during wave four, and all-cause deaths peaked at 1,663 during wave two.

The investigators also analyzed how unvaccinated patients fared, compared with the fully vaccinated and the fully vaccinated-plus (that is, patients with one or more additional doses). During waves five and six, unvaccinated patients were 4.3 times more likely to end up in the ICU than fully vaccinated patients and were 12.2 times more likely than fully vaccinated-plus patients. Likewise, the rate for all-cause in-hospital death for unvaccinated patients was 3.9 times greater than that for fully vaccinated patients and 15.1 times greater than that for fully vaccinated-plus patients.

The effect of vaccines emerged in waves three and four, said Dr. Frenette. “We started to see really, really significant protection and benefit from the vaccine, not only in incidence of admission but also in the incidence of complications of ICU care, ventilation, and mortality.”

Results for pediatric patients were similar to those for adults, Dr. Thampi noted. During waves five and six, overall admissions peaked, but the share of ICU admissions decreased to 9.4% from 18.1%, which was the rate during the previous four waves (OR, 0.47).

“What’s important is how pediatric hospitalizations changed over the course of the various waves,” said Dr. Thampi.

“Where we saw the highest admissions during the early Omicron dominance, we actually had the lowest numbers of hospitalizations with death and admissions into ICUs.”
 

Doing more with the data

David Fisman, MD, MPH, a professor of epidemiology at the University of Toronto, said, “This is a study that shows us how tremendously dramatic the effects of the COVID-19 vaccine were in terms of saving lives during the pandemic.” Dr. Fisman was not involved in the study.

But CNISP, which receives funding from Public Health Agency of Canada, could do more with the data it collects to better protect the public from COVID-19 and other nosocomial infections, Dr. Fisman said.

“The first problematic thing about this paper is that Canadians are paying for a surveillance system that looks at risks of acquiring infections, including COVID-19 infections, in the hospital, but that data is not fed back to the people paying for its production,” he said.

“So, Canadians don’t have the ability to really understand in real time how much risk they’re experiencing via going to the hospital for some other reason.”

The study was independently supported. Dr. Frenette and Dr. Thampi report no relevant financial relationships. Dr. Fisman has disclosed financial relationships with Pfizer, AstraZeneca, Sanofi, Seqirus, Merck, the Ontario Nurses Association, and the Elementary Teachers’ Federation of Ontario.

A version of this article first appeared on Medscape.com.