MDedge Rheumatology

Booster shots to ramp up protection against COVID-19 infection are slated to begin the week of Sept. 20, the Biden administration announced at a press briefing August 18.

Those who received the Pfizer-BioNTech and Moderna vaccines would be eligible to get a booster shot 8 months after they received the second dose of those vaccines, officials said. Information on boosters for those who got the one-dose Johnson & Johnson vaccine will be forthcoming.

“We anticipate a booster will [also] likely be needed,” said U.S. Surgeon General Vivek Murthy, MD. The J&J vaccine was not available in the U.S. until March, he said, and ‘’we expect more data on J&J in the coming weeks, so that plan is coming.”

The plan for boosters for the two mRNA vaccines is pending the FDA’s conducting of an independent review and authorizing the third dose of the Moderna and Pfizer-BioNTech vaccines, as well as an advisory committee of the CDC making the recommendation.

“We know that even highly effective vaccines become less effective over time,” Dr. Murthy said. “Having reviewed the most current data, it is now our clinical judgment that the time to lay out a plan for the COVID-19 boosters is now.”

Research released Aug. 18 shows waning effectiveness of the two mRNA vaccines.

At the briefing, Dr. Murthy and others continually reassured listeners that while effectiveness against infection declines, the vaccines continue to protect against severe infections, hospitalizations, and death.

“If you are fully vaccinated, you still have a high degree of protection against the worst outcomes,” Dr. Murthy said.
 

Data driving the plan

CDC Director Rochelle Walensky, MD, cited three research studies published Aug. 18 in the CDC’s Morbidity and Mortality Weekly Report that helped to drive the decision to recommend boosters.

Analysis of nursing home COVID-19 data from the CDC’s National Healthcare Safety Network showed a significant decline in the effectiveness of the full mRNA vaccine against lab-confirmed COVID-19 infection, from 74.7% before the Delta variant (March 1-May 9, 2021) to 53% when the Delta variant became predominant in the United States. The analysis during the Delta dominant period included 85,000 weekly reports from nearly 15,000 facilities.

Another study looked at more than 10 million New York adults who had been fully vaccinated with either the Moderna, Pfizer, or J&J vaccine by July 25. During the period from May 3 to July 25, overall, the age-adjusted vaccine effectiveness against infection decreased from 91.7% to 79.8%.

Vaccine effectiveness against hospitalization remains high, another study found. An analysis of 1,129 patients who had gotten two doses of an mRNA vaccine showed vaccine effectiveness against hospitalization after 24 weeks. It was 86% at weeks 2-12 and 84% at weeks 13-24.
 

Immunologic facts

Immunologic information also points to the need for a booster, said Anthony Fauci, MD, the chief medical advisor to the president and director of the National Institute of Allergy and Infectious Diseases.

“Antibody levels decline over time,” he said, “and higher antibody levels are associated with higher efficacy of the vaccine. Higher levels of antibody may be needed to protect against Delta.”

A booster increased antibody levels by ‘’at least tenfold and possibly more,” he said. And higher levels of antibody may be required to protect against Delta. Taken together, he said, the data support the use of a booster to increase the overall level of protection.
 

Booster details

“We will make sure it is convenient and easy to get the booster shot,” said Jeff Zients, the White House COVID-19 response coordinator. As with the previous immunization, he said, the booster will be free, and no one will be asked about immigration status.

The plan for booster shots is an attempt to stay ahead of the virus, officials stressed
 

Big picture

Not everyone agrees with the booster dose idea. At a World Health Organization briefing Aug. 18, WHO’s Chief Scientist Soumya Swaminathan, MD, an Indian pediatrician, said that the right thing to do right now ‘’is to wait for the science to tell us when boosters, which groups of people, and which vaccines need boosters.”

Like others, she also broached the ‘’moral and ethical argument of giving people third doses, when they’re already well protected and while the rest of the world is waiting for their primary immunization.”

Dr. Swaminathan does see a role for boosters to protect immunocompromised people but noted that ‘’that’s a small number of people.” Widespread boosters ‘’will only lead to more variants, to more escape variants, and perhaps we’re heading into more dire situations.”



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

Booster shots to ramp up protection against COVID-19 infection are slated to begin the week of Sept. 20, the Biden administration announced at a press briefing August 18.

Those who received the Pfizer-BioNTech and Moderna vaccines would be eligible to get a booster shot 8 months after they received the second dose of those vaccines, officials said. Information on boosters for those who got the one-dose Johnson & Johnson vaccine will be forthcoming.

“We anticipate a booster will [also] likely be needed,” said U.S. Surgeon General Vivek Murthy, MD. The J&J vaccine was not available in the U.S. until March, he said, and ‘’we expect more data on J&J in the coming weeks, so that plan is coming.”

The plan for boosters for the two mRNA vaccines is pending the FDA’s conducting of an independent review and authorizing the third dose of the Moderna and Pfizer-BioNTech vaccines, as well as an advisory committee of the CDC making the recommendation.

“We know that even highly effective vaccines become less effective over time,” Dr. Murthy said. “Having reviewed the most current data, it is now our clinical judgment that the time to lay out a plan for the COVID-19 boosters is now.”

Research released Aug. 18 shows waning effectiveness of the two mRNA vaccines.

At the briefing, Dr. Murthy and others continually reassured listeners that while effectiveness against infection declines, the vaccines continue to protect against severe infections, hospitalizations, and death.

“If you are fully vaccinated, you still have a high degree of protection against the worst outcomes,” Dr. Murthy said.
 

Data driving the plan

CDC Director Rochelle Walensky, MD, cited three research studies published Aug. 18 in the CDC’s Morbidity and Mortality Weekly Report that helped to drive the decision to recommend boosters.

Analysis of nursing home COVID-19 data from the CDC’s National Healthcare Safety Network showed a significant decline in the effectiveness of the full mRNA vaccine against lab-confirmed COVID-19 infection, from 74.7% before the Delta variant (March 1-May 9, 2021) to 53% when the Delta variant became predominant in the United States. The analysis during the Delta dominant period included 85,000 weekly reports from nearly 15,000 facilities.

Another study looked at more than 10 million New York adults who had been fully vaccinated with either the Moderna, Pfizer, or J&J vaccine by July 25. During the period from May 3 to July 25, overall, the age-adjusted vaccine effectiveness against infection decreased from 91.7% to 79.8%.

Vaccine effectiveness against hospitalization remains high, another study found. An analysis of 1,129 patients who had gotten two doses of an mRNA vaccine showed vaccine effectiveness against hospitalization after 24 weeks. It was 86% at weeks 2-12 and 84% at weeks 13-24.
 

Immunologic facts

Immunologic information also points to the need for a booster, said Anthony Fauci, MD, the chief medical advisor to the president and director of the National Institute of Allergy and Infectious Diseases.

“Antibody levels decline over time,” he said, “and higher antibody levels are associated with higher efficacy of the vaccine. Higher levels of antibody may be needed to protect against Delta.”

A booster increased antibody levels by ‘’at least tenfold and possibly more,” he said. And higher levels of antibody may be required to protect against Delta. Taken together, he said, the data support the use of a booster to increase the overall level of protection.
 

Booster details

“We will make sure it is convenient and easy to get the booster shot,” said Jeff Zients, the White House COVID-19 response coordinator. As with the previous immunization, he said, the booster will be free, and no one will be asked about immigration status.

The plan for booster shots is an attempt to stay ahead of the virus, officials stressed
 

Big picture

Not everyone agrees with the booster dose idea. At a World Health Organization briefing Aug. 18, WHO’s Chief Scientist Soumya Swaminathan, MD, an Indian pediatrician, said that the right thing to do right now ‘’is to wait for the science to tell us when boosters, which groups of people, and which vaccines need boosters.”

Like others, she also broached the ‘’moral and ethical argument of giving people third doses, when they’re already well protected and while the rest of the world is waiting for their primary immunization.”

Dr. Swaminathan does see a role for boosters to protect immunocompromised people but noted that ‘’that’s a small number of people.” Widespread boosters ‘’will only lead to more variants, to more escape variants, and perhaps we’re heading into more dire situations.”



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

Booster shots to ramp up protection against COVID-19 infection are slated to begin the week of Sept. 20, the Biden administration announced at a press briefing August 18.

Those who received the Pfizer-BioNTech and Moderna vaccines would be eligible to get a booster shot 8 months after they received the second dose of those vaccines, officials said. Information on boosters for those who got the one-dose Johnson & Johnson vaccine will be forthcoming.

“We anticipate a booster will [also] likely be needed,” said U.S. Surgeon General Vivek Murthy, MD. The J&J vaccine was not available in the U.S. until March, he said, and ‘’we expect more data on J&J in the coming weeks, so that plan is coming.”

The plan for boosters for the two mRNA vaccines is pending the FDA’s conducting of an independent review and authorizing the third dose of the Moderna and Pfizer-BioNTech vaccines, as well as an advisory committee of the CDC making the recommendation.

“We know that even highly effective vaccines become less effective over time,” Dr. Murthy said. “Having reviewed the most current data, it is now our clinical judgment that the time to lay out a plan for the COVID-19 boosters is now.”

Research released Aug. 18 shows waning effectiveness of the two mRNA vaccines.

At the briefing, Dr. Murthy and others continually reassured listeners that while effectiveness against infection declines, the vaccines continue to protect against severe infections, hospitalizations, and death.

“If you are fully vaccinated, you still have a high degree of protection against the worst outcomes,” Dr. Murthy said.
 

Data driving the plan

CDC Director Rochelle Walensky, MD, cited three research studies published Aug. 18 in the CDC’s Morbidity and Mortality Weekly Report that helped to drive the decision to recommend boosters.

Analysis of nursing home COVID-19 data from the CDC’s National Healthcare Safety Network showed a significant decline in the effectiveness of the full mRNA vaccine against lab-confirmed COVID-19 infection, from 74.7% before the Delta variant (March 1-May 9, 2021) to 53% when the Delta variant became predominant in the United States. The analysis during the Delta dominant period included 85,000 weekly reports from nearly 15,000 facilities.

Another study looked at more than 10 million New York adults who had been fully vaccinated with either the Moderna, Pfizer, or J&J vaccine by July 25. During the period from May 3 to July 25, overall, the age-adjusted vaccine effectiveness against infection decreased from 91.7% to 79.8%.

Vaccine effectiveness against hospitalization remains high, another study found. An analysis of 1,129 patients who had gotten two doses of an mRNA vaccine showed vaccine effectiveness against hospitalization after 24 weeks. It was 86% at weeks 2-12 and 84% at weeks 13-24.
 

Immunologic facts

Immunologic information also points to the need for a booster, said Anthony Fauci, MD, the chief medical advisor to the president and director of the National Institute of Allergy and Infectious Diseases.

“Antibody levels decline over time,” he said, “and higher antibody levels are associated with higher efficacy of the vaccine. Higher levels of antibody may be needed to protect against Delta.”

A booster increased antibody levels by ‘’at least tenfold and possibly more,” he said. And higher levels of antibody may be required to protect against Delta. Taken together, he said, the data support the use of a booster to increase the overall level of protection.
 

Booster details

“We will make sure it is convenient and easy to get the booster shot,” said Jeff Zients, the White House COVID-19 response coordinator. As with the previous immunization, he said, the booster will be free, and no one will be asked about immigration status.

The plan for booster shots is an attempt to stay ahead of the virus, officials stressed
 

Big picture

Not everyone agrees with the booster dose idea. At a World Health Organization briefing Aug. 18, WHO’s Chief Scientist Soumya Swaminathan, MD, an Indian pediatrician, said that the right thing to do right now ‘’is to wait for the science to tell us when boosters, which groups of people, and which vaccines need boosters.”

Like others, she also broached the ‘’moral and ethical argument of giving people third doses, when they’re already well protected and while the rest of the world is waiting for their primary immunization.”

Dr. Swaminathan does see a role for boosters to protect immunocompromised people but noted that ‘’that’s a small number of people.” Widespread boosters ‘’will only lead to more variants, to more escape variants, and perhaps we’re heading into more dire situations.”



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

Preliminary data from seven states suggests that breakthrough COVID-19 infections among vaccinated people may be on the rise because of the more contagious Delta variant.

Breakthrough cases accounted for about one in five newly diagnosed cases in six of the states, according to the New York Times. Hospitalizations and deaths among vaccinated people may be higher than previously thought as well.

“Remember when the early vaccine studies came out, it was like nobody gets hospitalized, nobody dies,” Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, said in an interview. “That clearly is not true.”

The New York Times analyzed data in seven states – California, Colorado, Massachusetts, Oregon, Utah, Vermont, and Virginia – that are tracking the most detailed information. The trends in these states may not reflect the numbers throughout the country, the newspaper reported.

Even still, the numbers back up the idea that vaccinated people may need booster shots this fall to support their earlier vaccine doses. Federal health officials are scheduled to approve the extra shots in coming weeks, potentially in September. The first people to receive booster shots will likely be health care workers and nursing home residents who took the first vaccines in December and January.

“If the chances of a breakthrough infection have gone up considerably, and I think the evidence is clear that they have, and the level of protection against severe illness is no longer as robust as it was, I think the case for boosters goes up pretty quickly,” Dr. Wachter said.

Previous analyses of breakthrough cases included data from June and earlier, the newspaper reported. But since July, COVID-19 cases have soared again because of the Delta variant, and the most recent numbers show an uptick among vaccinated people. In Los Angeles County, for instance, fully vaccinated people account for 20% of new COVID-19 cases, which is up from 11% in May, 5% in April, and 2% in March, according to a late July report from the Los Angeles County Department of Public Health.

What’s more, breakthrough infections in the seven states accounted for 12%-24% of COVID-19 hospitalizations in those states. About 8,000 breakthrough hospitalizations have been reported to the CDC. Still, the overall numbers remain low – in California, for instance, about 1,615 people have been hospitalized with breakthrough infections, which accounts for 0.007% of the state’s 22 million vaccinated people, the Times reported.

The breakthrough infections appear to be more severe among vaccinated people who are older or have weakened immune systems. About 74% of breakthrough cases are among adults 65 or older, the CDC reported.

The increase may shift how vaccinated people see their risks for infection and interact with loved ones. Public health officials have suggested that people follow some COVID-19 safety protocols again, such as wearing masks in public indoor spaces regardless of vaccination status.

As the Delta variant continues to circulate this fall, public health researchers will be researching more about breakthrough cases among vaccinated people, including whether they have prolonged symptoms and how easily they may pass the virus to others.

“I think some of us have been challenged by the numbers of clusters that we’ve seen,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told this news organization.

“I think that really needs to be examined more,” he said.

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

Preliminary data from seven states suggests that breakthrough COVID-19 infections among vaccinated people may be on the rise because of the more contagious Delta variant.

Breakthrough cases accounted for about one in five newly diagnosed cases in six of the states, according to the New York Times. Hospitalizations and deaths among vaccinated people may be higher than previously thought as well.

“Remember when the early vaccine studies came out, it was like nobody gets hospitalized, nobody dies,” Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, said in an interview. “That clearly is not true.”

The New York Times analyzed data in seven states – California, Colorado, Massachusetts, Oregon, Utah, Vermont, and Virginia – that are tracking the most detailed information. The trends in these states may not reflect the numbers throughout the country, the newspaper reported.

Even still, the numbers back up the idea that vaccinated people may need booster shots this fall to support their earlier vaccine doses. Federal health officials are scheduled to approve the extra shots in coming weeks, potentially in September. The first people to receive booster shots will likely be health care workers and nursing home residents who took the first vaccines in December and January.

“If the chances of a breakthrough infection have gone up considerably, and I think the evidence is clear that they have, and the level of protection against severe illness is no longer as robust as it was, I think the case for boosters goes up pretty quickly,” Dr. Wachter said.

Previous analyses of breakthrough cases included data from June and earlier, the newspaper reported. But since July, COVID-19 cases have soared again because of the Delta variant, and the most recent numbers show an uptick among vaccinated people. In Los Angeles County, for instance, fully vaccinated people account for 20% of new COVID-19 cases, which is up from 11% in May, 5% in April, and 2% in March, according to a late July report from the Los Angeles County Department of Public Health.

What’s more, breakthrough infections in the seven states accounted for 12%-24% of COVID-19 hospitalizations in those states. About 8,000 breakthrough hospitalizations have been reported to the CDC. Still, the overall numbers remain low – in California, for instance, about 1,615 people have been hospitalized with breakthrough infections, which accounts for 0.007% of the state’s 22 million vaccinated people, the Times reported.

The breakthrough infections appear to be more severe among vaccinated people who are older or have weakened immune systems. About 74% of breakthrough cases are among adults 65 or older, the CDC reported.

The increase may shift how vaccinated people see their risks for infection and interact with loved ones. Public health officials have suggested that people follow some COVID-19 safety protocols again, such as wearing masks in public indoor spaces regardless of vaccination status.

As the Delta variant continues to circulate this fall, public health researchers will be researching more about breakthrough cases among vaccinated people, including whether they have prolonged symptoms and how easily they may pass the virus to others.

“I think some of us have been challenged by the numbers of clusters that we’ve seen,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told this news organization.

“I think that really needs to be examined more,” he said.

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

Preliminary data from seven states suggests that breakthrough COVID-19 infections among vaccinated people may be on the rise because of the more contagious Delta variant.

Breakthrough cases accounted for about one in five newly diagnosed cases in six of the states, according to the New York Times. Hospitalizations and deaths among vaccinated people may be higher than previously thought as well.

“Remember when the early vaccine studies came out, it was like nobody gets hospitalized, nobody dies,” Robert Wachter, MD, chairman of the department of medicine at the University of California, San Francisco, said in an interview. “That clearly is not true.”

The New York Times analyzed data in seven states – California, Colorado, Massachusetts, Oregon, Utah, Vermont, and Virginia – that are tracking the most detailed information. The trends in these states may not reflect the numbers throughout the country, the newspaper reported.

Even still, the numbers back up the idea that vaccinated people may need booster shots this fall to support their earlier vaccine doses. Federal health officials are scheduled to approve the extra shots in coming weeks, potentially in September. The first people to receive booster shots will likely be health care workers and nursing home residents who took the first vaccines in December and January.

“If the chances of a breakthrough infection have gone up considerably, and I think the evidence is clear that they have, and the level of protection against severe illness is no longer as robust as it was, I think the case for boosters goes up pretty quickly,” Dr. Wachter said.

Previous analyses of breakthrough cases included data from June and earlier, the newspaper reported. But since July, COVID-19 cases have soared again because of the Delta variant, and the most recent numbers show an uptick among vaccinated people. In Los Angeles County, for instance, fully vaccinated people account for 20% of new COVID-19 cases, which is up from 11% in May, 5% in April, and 2% in March, according to a late July report from the Los Angeles County Department of Public Health.

What’s more, breakthrough infections in the seven states accounted for 12%-24% of COVID-19 hospitalizations in those states. About 8,000 breakthrough hospitalizations have been reported to the CDC. Still, the overall numbers remain low – in California, for instance, about 1,615 people have been hospitalized with breakthrough infections, which accounts for 0.007% of the state’s 22 million vaccinated people, the Times reported.

The breakthrough infections appear to be more severe among vaccinated people who are older or have weakened immune systems. About 74% of breakthrough cases are among adults 65 or older, the CDC reported.

The increase may shift how vaccinated people see their risks for infection and interact with loved ones. Public health officials have suggested that people follow some COVID-19 safety protocols again, such as wearing masks in public indoor spaces regardless of vaccination status.

As the Delta variant continues to circulate this fall, public health researchers will be researching more about breakthrough cases among vaccinated people, including whether they have prolonged symptoms and how easily they may pass the virus to others.

“I think some of us have been challenged by the numbers of clusters that we’ve seen,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told this news organization.

“I think that really needs to be examined more,” he said.

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

With the Delta variant surging across the country, already spread-thin health care workers are facing even sicker –and younger – Americans affected by COVID-19 than at the start of the pandemic.

While the exact toll the pandemic will take on essential workers will remain unknown, one thing is clear: The COVID-19 outbreak they’re experiencing right now on the front lines is a far cry from the original strain. They’re scared, exasperated, and crying out for us to pay attention and get vaccinated.

Five health care workers told this news organization about their experiences working the front lines amid the recent surge and what they think needs to happen – fast.
 

COVID-19 perspective from a paramedic in Connecticut

Michael Battistelli has been an emergency medical services worker for over 20 years and a licensed paramedic in Stratford, Conn., for a decade. He’s also the father of a 5-year-old daughter who isn’t eligible for a vaccination yet. For him, every day has been the same since the start of the pandemic: Surgical mask, N95 mask, face shield, change clothes before going home, and shower as soon as he walks in the door. He’s worried about Delta right now and wants you to be, too.

What keeps him up at night: “It seems like the last time, COVID-19 hit the Pacific Northwest and Northeast first. I hope it’s not the reverse and that it isn’t working its way back up to us here in Connecticut. I’ll add that if we start seeing young people dying, that might be it for me. That might be my final stand as an EMS.”

Why he’s frustrated: “For people to say COVID-19 isn’t real is mind-blowing. I’ve been at this for over a year, and all I think about is how to keep my daughter safe and protect my parents, especially my mom, who is a cancer survivor. When this first started, I brought people into the hospital who thought they would be fine after a day or week in the hospital. They ended up being on ventilators for months – and these were healthy people.”

What he wants to see: “I try not to judge people, but please understand how hard health care workers are working. We’re fatigued and burned out, and we are begging you: Please get vaccinated.”
 

COVID-19 perspective from an ICU director in Tennessee

Todd Rice, MD, FCCP, is an associate professor of medicine in the division of allergy, pulmonary and critical care at Vanderbilt Medical Center in Nashville, Tenn. While this father of two – ages 15 and 17 – trained for a pandemic, specifically Ebola and H1N1, the sheer volume of young COVID-19 patients in the ICU right now is taking a huge toll on him and his staff.

Why he’s frustrated: “First, there are a group of people that are adamantly against getting vaccinated. It doesn’t matter what we do or say. Second, a lot of people are confused and tell me that they don’t have somebody they trust to answer their questions about the vaccine. Third, some of this is driven by our colleagues: In the last 2 weeks, eight pregnant women with COVID-19 were admitted to our ICU. At least six said that their [obstetrician] told them not to get the vaccine while pregnant. That myth is still out there.”

What’s going on in the ICU: “I want people to know that our unvaccinated infected COVID-19 patients are the sickest patients we take care of. Their condition can change on a dime. We think they’re getting better, and suddenly we turn around and they’re near death or they die in seconds. What’s hard for our staff is that many of these patients have been with us for several weeks, and we get to know them. So when this happens, it hurts us even more because we’ve gotten to know them.”

What we need to do: “While it may take time, we have to talk to vaccine-hesitant people one by one and ask them what questions they have and then provide them with the answers they need. I think the next 6 months is going to be all about getting people who are still movable on this and get them to be comfortable that the vaccine is safe, that we didn’t cut corners. Yes, it was developed faster than anything we’ve ever done before, but that’s because it had to be.”
 

COVID-19 perspective from a cardiopulmonary doctor in Florida

Yvonne Billings, MD, director of cardiopulmonary medicine at Cleveland Clinic Martin Health in Stuart, Fla., says the “explosion” of COVID-19 cases right after July 4 has left her and her staff emotionally and physically overwhelmed.

What worries her: “We have great PPE, but we’re all worries because Delta is so contagious, and our colleagues have gotten it. We’ll eat lunch next to each other – socially distanced, of course – and we won’t know if we’ve gotten it by just sitting down to eat.”

What she wants us to do – now: “Everyone needs to listen to the real medical science and understand how much this is impacting everyone’s care. For example, if you need to come to the hospital for something other than COVID-19, you will receive slower care because everyone is so tied up caring for COVID-19 patients.”

Health care workers need to get on board, too: “I look at some of my respiratory therapists who chose not to be vaccinated until this last surge. Many told me that when the younger patients started coming in, they could relate to that. One said: ‘I see this gentleman is 27. I’m 27. I could be in the exact same position.’ I don’t want to see anyone get sick, but I’m hoping that when people see that this affects anyone at any age, they can push politics and what they thought was true about the vaccine aside, and make different choices and move forward.”
 

COVID-19 perspective from a registered nurse in Louisiana

Gina McNemar, 37, an ICU nurse at Baton Rouge General Medical Center in Baton Rouge, La., is wiped out. Her ICU unit is currently full of COVID-19 patients. This mom of 5-year-old twins is so upset about the onslaught of patients in her unit that she sent an email to the CEO of the hospital, which he then shared on Facebook with hundreds of followers. From the email: “This Covid is different. Let me repeat myself: THIS COVID IS NOT THE SAME. ... For the first time since April 2020, I kneeled on top of a patient in the middle of CPR and saw myself. She was 41 years old, no comorbidities, a full life ahead of her. The first time we fought Covid, everyone was old and sickly. They weren’t ‘me.’ This sweet woman was ‘me.’ We ran a full code on her for 1 hour and 26 minutes in front of her fiancé. He cried out to God to save her. He cried out to us to save her. We did everything in our power to save her. We weren’t able to. Three nurses, a pharmacy tech, an x-ray tech, and our HMG doctor hugged, prayed, and cried together after. She was living her life, got Covid, and died.”

Why she wants people to pay attention: “Our COVID-19 patients are young, they’re healthy, they’re able to answer our questions and immediately crash. We don’t have time to catch our breath between one code to the next. This COVID-19 is a much more violent disease, and I can no longer keep quiet. Someone has to say it. Someone has to say, ‘You can believe what you want to believe,’ but I’m seeing it with my own eyes, I’m holding their hands while they die, I’m bagging their body for the morgue. See this crisis through my eyes – please!”

What’s happening with her coworkers: “We’ve had some pretty bad days. We’re all crying and we’re afraid for each other now. We feel like it could be any of us at any point. I’m feeling that I don’t want to let it get to me, but it is. At home, we pray every night. The other night, one of my twins said: ‘I pray that you don’t get coronavirus and die.’ I can’t help but think: 5-year-olds should pray for unicorns and rainbows, not that their mom could die at work.”

Please stop playing politics: “America has become so divided and the vaccine somehow became the evil thing instead of the fact that the vaccine is the savior. I waited in line to get my vaccine because the scientists came up with something to end all this, but not everyone sees it that way. I feel like people don’t want to see and it shouldn’t matter if you’re a Republican or Democrat – after all, Biden is vaccinated [and] Trump is vaccinated.”
 

COVID-19 perspective from an ED doctor in New York City

Amanda Smith, MD, an ED doctor at Staten Island University Hospital in New York, says she’s sensing a “slow wave coming” when it comes to the Delta variant. The mom of three kids (she has 10-year-old twins and a 12-year-old) thinks often of the first signs of COVID-19 in 2020 and hopes that there won’t be a repeat surge like the initial one in New York City.

It’s hard not to feel frustrated: “I’m annoyed about the Delta variant. Of course, I’ve experienced the ‘I’m not getting the vaccine’ argument, and I’ve been at this long enough that I’m able to compartmentalize my own feelings, but I’m worn down, and I’m aware that I have compassion fatigue. When people complain about their COVID-19 symptoms and say things like ‘If I knew I would feel this horrible, I would have gotten the vaccine,’ I can’t help but feel that this was avoidable. It’s hard to talk to those people. I want to say ‘600,000 dead people weren’t enough to get vaccinated?’ ”

The people avoiding the vaccine: “There are the absolute deniers who will never get vaccinated and aren’t going to change their minds. Then there are the people who feel invincible, and then there are the folks who think that COVID-19 isn’t that bad, it’s just like the flu, it’s only old people dying and they’re not getting information from an appropriate source. It’s not the flu, it does kill you. Delta kills younger people, and it’s very easy to spread. Every one person who was infected with the original strain could infect two to three others. The Delta variant can infect 8-9, and measles, at 13, is the most contagious, so we need to keep reminding people about this.”

It’s not just about you: “Vaccination campaigns were never about the individual. We live together in a civilized society, and the vaccine is something you do for each other. People don’t understand the importance of breaking the chain of transmission and doing this to help each other and eradicate the spread. I just don’t understand what happened to us that we forgot this.”

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

With the Delta variant surging across the country, already spread-thin health care workers are facing even sicker –and younger – Americans affected by COVID-19 than at the start of the pandemic.

While the exact toll the pandemic will take on essential workers will remain unknown, one thing is clear: The COVID-19 outbreak they’re experiencing right now on the front lines is a far cry from the original strain. They’re scared, exasperated, and crying out for us to pay attention and get vaccinated.

Five health care workers told this news organization about their experiences working the front lines amid the recent surge and what they think needs to happen – fast.
 

COVID-19 perspective from a paramedic in Connecticut

Michael Battistelli has been an emergency medical services worker for over 20 years and a licensed paramedic in Stratford, Conn., for a decade. He’s also the father of a 5-year-old daughter who isn’t eligible for a vaccination yet. For him, every day has been the same since the start of the pandemic: Surgical mask, N95 mask, face shield, change clothes before going home, and shower as soon as he walks in the door. He’s worried about Delta right now and wants you to be, too.

What keeps him up at night: “It seems like the last time, COVID-19 hit the Pacific Northwest and Northeast first. I hope it’s not the reverse and that it isn’t working its way back up to us here in Connecticut. I’ll add that if we start seeing young people dying, that might be it for me. That might be my final stand as an EMS.”

Why he’s frustrated: “For people to say COVID-19 isn’t real is mind-blowing. I’ve been at this for over a year, and all I think about is how to keep my daughter safe and protect my parents, especially my mom, who is a cancer survivor. When this first started, I brought people into the hospital who thought they would be fine after a day or week in the hospital. They ended up being on ventilators for months – and these were healthy people.”

What he wants to see: “I try not to judge people, but please understand how hard health care workers are working. We’re fatigued and burned out, and we are begging you: Please get vaccinated.”
 

COVID-19 perspective from an ICU director in Tennessee

Todd Rice, MD, FCCP, is an associate professor of medicine in the division of allergy, pulmonary and critical care at Vanderbilt Medical Center in Nashville, Tenn. While this father of two – ages 15 and 17 – trained for a pandemic, specifically Ebola and H1N1, the sheer volume of young COVID-19 patients in the ICU right now is taking a huge toll on him and his staff.

Why he’s frustrated: “First, there are a group of people that are adamantly against getting vaccinated. It doesn’t matter what we do or say. Second, a lot of people are confused and tell me that they don’t have somebody they trust to answer their questions about the vaccine. Third, some of this is driven by our colleagues: In the last 2 weeks, eight pregnant women with COVID-19 were admitted to our ICU. At least six said that their [obstetrician] told them not to get the vaccine while pregnant. That myth is still out there.”

What’s going on in the ICU: “I want people to know that our unvaccinated infected COVID-19 patients are the sickest patients we take care of. Their condition can change on a dime. We think they’re getting better, and suddenly we turn around and they’re near death or they die in seconds. What’s hard for our staff is that many of these patients have been with us for several weeks, and we get to know them. So when this happens, it hurts us even more because we’ve gotten to know them.”

What we need to do: “While it may take time, we have to talk to vaccine-hesitant people one by one and ask them what questions they have and then provide them with the answers they need. I think the next 6 months is going to be all about getting people who are still movable on this and get them to be comfortable that the vaccine is safe, that we didn’t cut corners. Yes, it was developed faster than anything we’ve ever done before, but that’s because it had to be.”
 

COVID-19 perspective from a cardiopulmonary doctor in Florida

Yvonne Billings, MD, director of cardiopulmonary medicine at Cleveland Clinic Martin Health in Stuart, Fla., says the “explosion” of COVID-19 cases right after July 4 has left her and her staff emotionally and physically overwhelmed.

What worries her: “We have great PPE, but we’re all worries because Delta is so contagious, and our colleagues have gotten it. We’ll eat lunch next to each other – socially distanced, of course – and we won’t know if we’ve gotten it by just sitting down to eat.”

What she wants us to do – now: “Everyone needs to listen to the real medical science and understand how much this is impacting everyone’s care. For example, if you need to come to the hospital for something other than COVID-19, you will receive slower care because everyone is so tied up caring for COVID-19 patients.”

Health care workers need to get on board, too: “I look at some of my respiratory therapists who chose not to be vaccinated until this last surge. Many told me that when the younger patients started coming in, they could relate to that. One said: ‘I see this gentleman is 27. I’m 27. I could be in the exact same position.’ I don’t want to see anyone get sick, but I’m hoping that when people see that this affects anyone at any age, they can push politics and what they thought was true about the vaccine aside, and make different choices and move forward.”
 

COVID-19 perspective from a registered nurse in Louisiana

Gina McNemar, 37, an ICU nurse at Baton Rouge General Medical Center in Baton Rouge, La., is wiped out. Her ICU unit is currently full of COVID-19 patients. This mom of 5-year-old twins is so upset about the onslaught of patients in her unit that she sent an email to the CEO of the hospital, which he then shared on Facebook with hundreds of followers. From the email: “This Covid is different. Let me repeat myself: THIS COVID IS NOT THE SAME. ... For the first time since April 2020, I kneeled on top of a patient in the middle of CPR and saw myself. She was 41 years old, no comorbidities, a full life ahead of her. The first time we fought Covid, everyone was old and sickly. They weren’t ‘me.’ This sweet woman was ‘me.’ We ran a full code on her for 1 hour and 26 minutes in front of her fiancé. He cried out to God to save her. He cried out to us to save her. We did everything in our power to save her. We weren’t able to. Three nurses, a pharmacy tech, an x-ray tech, and our HMG doctor hugged, prayed, and cried together after. She was living her life, got Covid, and died.”

Why she wants people to pay attention: “Our COVID-19 patients are young, they’re healthy, they’re able to answer our questions and immediately crash. We don’t have time to catch our breath between one code to the next. This COVID-19 is a much more violent disease, and I can no longer keep quiet. Someone has to say it. Someone has to say, ‘You can believe what you want to believe,’ but I’m seeing it with my own eyes, I’m holding their hands while they die, I’m bagging their body for the morgue. See this crisis through my eyes – please!”

What’s happening with her coworkers: “We’ve had some pretty bad days. We’re all crying and we’re afraid for each other now. We feel like it could be any of us at any point. I’m feeling that I don’t want to let it get to me, but it is. At home, we pray every night. The other night, one of my twins said: ‘I pray that you don’t get coronavirus and die.’ I can’t help but think: 5-year-olds should pray for unicorns and rainbows, not that their mom could die at work.”

Please stop playing politics: “America has become so divided and the vaccine somehow became the evil thing instead of the fact that the vaccine is the savior. I waited in line to get my vaccine because the scientists came up with something to end all this, but not everyone sees it that way. I feel like people don’t want to see and it shouldn’t matter if you’re a Republican or Democrat – after all, Biden is vaccinated [and] Trump is vaccinated.”
 

COVID-19 perspective from an ED doctor in New York City

Amanda Smith, MD, an ED doctor at Staten Island University Hospital in New York, says she’s sensing a “slow wave coming” when it comes to the Delta variant. The mom of three kids (she has 10-year-old twins and a 12-year-old) thinks often of the first signs of COVID-19 in 2020 and hopes that there won’t be a repeat surge like the initial one in New York City.

It’s hard not to feel frustrated: “I’m annoyed about the Delta variant. Of course, I’ve experienced the ‘I’m not getting the vaccine’ argument, and I’ve been at this long enough that I’m able to compartmentalize my own feelings, but I’m worn down, and I’m aware that I have compassion fatigue. When people complain about their COVID-19 symptoms and say things like ‘If I knew I would feel this horrible, I would have gotten the vaccine,’ I can’t help but feel that this was avoidable. It’s hard to talk to those people. I want to say ‘600,000 dead people weren’t enough to get vaccinated?’ ”

The people avoiding the vaccine: “There are the absolute deniers who will never get vaccinated and aren’t going to change their minds. Then there are the people who feel invincible, and then there are the folks who think that COVID-19 isn’t that bad, it’s just like the flu, it’s only old people dying and they’re not getting information from an appropriate source. It’s not the flu, it does kill you. Delta kills younger people, and it’s very easy to spread. Every one person who was infected with the original strain could infect two to three others. The Delta variant can infect 8-9, and measles, at 13, is the most contagious, so we need to keep reminding people about this.”

It’s not just about you: “Vaccination campaigns were never about the individual. We live together in a civilized society, and the vaccine is something you do for each other. People don’t understand the importance of breaking the chain of transmission and doing this to help each other and eradicate the spread. I just don’t understand what happened to us that we forgot this.”

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

With the Delta variant surging across the country, already spread-thin health care workers are facing even sicker –and younger – Americans affected by COVID-19 than at the start of the pandemic.

While the exact toll the pandemic will take on essential workers will remain unknown, one thing is clear: The COVID-19 outbreak they’re experiencing right now on the front lines is a far cry from the original strain. They’re scared, exasperated, and crying out for us to pay attention and get vaccinated.

Five health care workers told this news organization about their experiences working the front lines amid the recent surge and what they think needs to happen – fast.
 

COVID-19 perspective from a paramedic in Connecticut

Michael Battistelli has been an emergency medical services worker for over 20 years and a licensed paramedic in Stratford, Conn., for a decade. He’s also the father of a 5-year-old daughter who isn’t eligible for a vaccination yet. For him, every day has been the same since the start of the pandemic: Surgical mask, N95 mask, face shield, change clothes before going home, and shower as soon as he walks in the door. He’s worried about Delta right now and wants you to be, too.

What keeps him up at night: “It seems like the last time, COVID-19 hit the Pacific Northwest and Northeast first. I hope it’s not the reverse and that it isn’t working its way back up to us here in Connecticut. I’ll add that if we start seeing young people dying, that might be it for me. That might be my final stand as an EMS.”

Why he’s frustrated: “For people to say COVID-19 isn’t real is mind-blowing. I’ve been at this for over a year, and all I think about is how to keep my daughter safe and protect my parents, especially my mom, who is a cancer survivor. When this first started, I brought people into the hospital who thought they would be fine after a day or week in the hospital. They ended up being on ventilators for months – and these were healthy people.”

What he wants to see: “I try not to judge people, but please understand how hard health care workers are working. We’re fatigued and burned out, and we are begging you: Please get vaccinated.”
 

COVID-19 perspective from an ICU director in Tennessee

Todd Rice, MD, FCCP, is an associate professor of medicine in the division of allergy, pulmonary and critical care at Vanderbilt Medical Center in Nashville, Tenn. While this father of two – ages 15 and 17 – trained for a pandemic, specifically Ebola and H1N1, the sheer volume of young COVID-19 patients in the ICU right now is taking a huge toll on him and his staff.

Why he’s frustrated: “First, there are a group of people that are adamantly against getting vaccinated. It doesn’t matter what we do or say. Second, a lot of people are confused and tell me that they don’t have somebody they trust to answer their questions about the vaccine. Third, some of this is driven by our colleagues: In the last 2 weeks, eight pregnant women with COVID-19 were admitted to our ICU. At least six said that their [obstetrician] told them not to get the vaccine while pregnant. That myth is still out there.”

What’s going on in the ICU: “I want people to know that our unvaccinated infected COVID-19 patients are the sickest patients we take care of. Their condition can change on a dime. We think they’re getting better, and suddenly we turn around and they’re near death or they die in seconds. What’s hard for our staff is that many of these patients have been with us for several weeks, and we get to know them. So when this happens, it hurts us even more because we’ve gotten to know them.”

What we need to do: “While it may take time, we have to talk to vaccine-hesitant people one by one and ask them what questions they have and then provide them with the answers they need. I think the next 6 months is going to be all about getting people who are still movable on this and get them to be comfortable that the vaccine is safe, that we didn’t cut corners. Yes, it was developed faster than anything we’ve ever done before, but that’s because it had to be.”
 

COVID-19 perspective from a cardiopulmonary doctor in Florida

Yvonne Billings, MD, director of cardiopulmonary medicine at Cleveland Clinic Martin Health in Stuart, Fla., says the “explosion” of COVID-19 cases right after July 4 has left her and her staff emotionally and physically overwhelmed.

What worries her: “We have great PPE, but we’re all worries because Delta is so contagious, and our colleagues have gotten it. We’ll eat lunch next to each other – socially distanced, of course – and we won’t know if we’ve gotten it by just sitting down to eat.”

What she wants us to do – now: “Everyone needs to listen to the real medical science and understand how much this is impacting everyone’s care. For example, if you need to come to the hospital for something other than COVID-19, you will receive slower care because everyone is so tied up caring for COVID-19 patients.”

Health care workers need to get on board, too: “I look at some of my respiratory therapists who chose not to be vaccinated until this last surge. Many told me that when the younger patients started coming in, they could relate to that. One said: ‘I see this gentleman is 27. I’m 27. I could be in the exact same position.’ I don’t want to see anyone get sick, but I’m hoping that when people see that this affects anyone at any age, they can push politics and what they thought was true about the vaccine aside, and make different choices and move forward.”
 

COVID-19 perspective from a registered nurse in Louisiana

Gina McNemar, 37, an ICU nurse at Baton Rouge General Medical Center in Baton Rouge, La., is wiped out. Her ICU unit is currently full of COVID-19 patients. This mom of 5-year-old twins is so upset about the onslaught of patients in her unit that she sent an email to the CEO of the hospital, which he then shared on Facebook with hundreds of followers. From the email: “This Covid is different. Let me repeat myself: THIS COVID IS NOT THE SAME. ... For the first time since April 2020, I kneeled on top of a patient in the middle of CPR and saw myself. She was 41 years old, no comorbidities, a full life ahead of her. The first time we fought Covid, everyone was old and sickly. They weren’t ‘me.’ This sweet woman was ‘me.’ We ran a full code on her for 1 hour and 26 minutes in front of her fiancé. He cried out to God to save her. He cried out to us to save her. We did everything in our power to save her. We weren’t able to. Three nurses, a pharmacy tech, an x-ray tech, and our HMG doctor hugged, prayed, and cried together after. She was living her life, got Covid, and died.”

Why she wants people to pay attention: “Our COVID-19 patients are young, they’re healthy, they’re able to answer our questions and immediately crash. We don’t have time to catch our breath between one code to the next. This COVID-19 is a much more violent disease, and I can no longer keep quiet. Someone has to say it. Someone has to say, ‘You can believe what you want to believe,’ but I’m seeing it with my own eyes, I’m holding their hands while they die, I’m bagging their body for the morgue. See this crisis through my eyes – please!”

What’s happening with her coworkers: “We’ve had some pretty bad days. We’re all crying and we’re afraid for each other now. We feel like it could be any of us at any point. I’m feeling that I don’t want to let it get to me, but it is. At home, we pray every night. The other night, one of my twins said: ‘I pray that you don’t get coronavirus and die.’ I can’t help but think: 5-year-olds should pray for unicorns and rainbows, not that their mom could die at work.”

Please stop playing politics: “America has become so divided and the vaccine somehow became the evil thing instead of the fact that the vaccine is the savior. I waited in line to get my vaccine because the scientists came up with something to end all this, but not everyone sees it that way. I feel like people don’t want to see and it shouldn’t matter if you’re a Republican or Democrat – after all, Biden is vaccinated [and] Trump is vaccinated.”
 

COVID-19 perspective from an ED doctor in New York City

Amanda Smith, MD, an ED doctor at Staten Island University Hospital in New York, says she’s sensing a “slow wave coming” when it comes to the Delta variant. The mom of three kids (she has 10-year-old twins and a 12-year-old) thinks often of the first signs of COVID-19 in 2020 and hopes that there won’t be a repeat surge like the initial one in New York City.

It’s hard not to feel frustrated: “I’m annoyed about the Delta variant. Of course, I’ve experienced the ‘I’m not getting the vaccine’ argument, and I’ve been at this long enough that I’m able to compartmentalize my own feelings, but I’m worn down, and I’m aware that I have compassion fatigue. When people complain about their COVID-19 symptoms and say things like ‘If I knew I would feel this horrible, I would have gotten the vaccine,’ I can’t help but feel that this was avoidable. It’s hard to talk to those people. I want to say ‘600,000 dead people weren’t enough to get vaccinated?’ ”

The people avoiding the vaccine: “There are the absolute deniers who will never get vaccinated and aren’t going to change their minds. Then there are the people who feel invincible, and then there are the folks who think that COVID-19 isn’t that bad, it’s just like the flu, it’s only old people dying and they’re not getting information from an appropriate source. It’s not the flu, it does kill you. Delta kills younger people, and it’s very easy to spread. Every one person who was infected with the original strain could infect two to three others. The Delta variant can infect 8-9, and measles, at 13, is the most contagious, so we need to keep reminding people about this.”

It’s not just about you: “Vaccination campaigns were never about the individual. We live together in a civilized society, and the vaccine is something you do for each other. People don’t understand the importance of breaking the chain of transmission and doing this to help each other and eradicate the spread. I just don’t understand what happened to us that we forgot this.”

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

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Since the COVID-19 pandemic began, I have received a growing number of inquiries about collection issues. For a variety of reasons, many patients seem increasingly reluctant to pay their medical bills. I’ve written many columns on keeping credit card numbers on file, and other techniques for keeping your accounts receivable in check; but despite your best efforts, there will always be a few deadbeats that you will need to pursue.

For the record, I am not speaking about patients who lost income due to the pandemic and are now struggling with debts, or otherwise have fallen on hard times and are unable to pay. I am addressing the problem of patients who are able to pay, but for whatever reason, do not.

The worst kinds of deadbeats are the ones who rob you twice; they accept payments from insurance companies and keep them. Such crooks must be pursued aggressively, with all the means at your disposal; but to reiterate the point I’ve tried to drive home repeatedly, the best cure is prevention.

You already know that you should collect as many fees as possible at the time of service. For cosmetic procedures you should require a substantial deposit in advance, with the balance due at the time of service. When that is impossible, maximize the chances you will be paid by making sure all available payment mechanisms are in place.

With my credit-card-on-file system that I’ve described many times, patients who fail to pay their credit card bill are the credit card company’s problem, not yours. In cases where you suspect fees might exceed credit card limits, you can arrange a realistic payment schedule in advance and have the patient fill out a credit application. You can find forms for this online at formswift.com, templates.office.com, and many other websites.

In some cases, it may be worth the trouble to run a background check. There are easy and affordable ways to do this. Dunn & Bradstreet, for example, will furnish a report containing payment records and details of any lawsuits, liens, and other legal actions for a nominal fee. The more financial information you have on file, the more leverage you have if a patient later balks at paying his or her balance.

For cosmetic work, always take before and after photos, and have all patients sign a written consent giving permission for the procedure, assuming full financial responsibility, and acknowledging that no guarantees have been given or implied. This defuses the common deadbeat tactics of claiming ignorance of personal financial obligations and professing dissatisfaction with the results.

Despite all your precautions, a deadbeat will inevitably slip through on occasion; but even then, you have options for extracting payment. Collection agencies are the traditional first line of attack for most medical practices. Ideally, your agency should specialize in handling medical accounts, so it will know exactly how much pressure to exert to avoid charges of harassment. Delinquent accounts should be submitted earlier rather than later to maximize the chances of success; my manager never allows an account to age more than 90 days, and if circumstances dictate, she refers them sooner than that.

When collection agencies fail, think about small claims court. You will need to learn the rules in your state, but in most states there is a small filing fee and a limit of $5,000 or so on claims. No attorneys are involved. If your paperwork is in order, the court will nearly always rule in your favor, but it will not provide the means for actual collection. In other words, you will still have to persuade the deadbeat to pay up. However, in many states a court order will give you the authority to attach a lien to property, or garnish wages, which often provides enough leverage to force payment.

What about those double-deadbeats who keep the insurance checks for themselves? First, check your third-party contract; sometimes the insurance company or HMO will be compelled to pay you directly and then go after the patient to get back its money. (They won’t volunteer this service, however – you’ll have to ask for it.)

If that’s not an option, consider reporting the misdirected payment to the Internal Revenue Service as income to the patient, by submitting a 1099 Miscellaneous Income form. Be sure to notify the deadbeat that you will be doing this. Sometimes the threat of such action will convince the individual to pay up; if not, at least you’ll have the satisfaction of knowing he or she will have to pay taxes on the money.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Since the COVID-19 pandemic began, I have received a growing number of inquiries about collection issues. For a variety of reasons, many patients seem increasingly reluctant to pay their medical bills. I’ve written many columns on keeping credit card numbers on file, and other techniques for keeping your accounts receivable in check; but despite your best efforts, there will always be a few deadbeats that you will need to pursue.

For the record, I am not speaking about patients who lost income due to the pandemic and are now struggling with debts, or otherwise have fallen on hard times and are unable to pay. I am addressing the problem of patients who are able to pay, but for whatever reason, do not.

The worst kinds of deadbeats are the ones who rob you twice; they accept payments from insurance companies and keep them. Such crooks must be pursued aggressively, with all the means at your disposal; but to reiterate the point I’ve tried to drive home repeatedly, the best cure is prevention.

You already know that you should collect as many fees as possible at the time of service. For cosmetic procedures you should require a substantial deposit in advance, with the balance due at the time of service. When that is impossible, maximize the chances you will be paid by making sure all available payment mechanisms are in place.

With my credit-card-on-file system that I’ve described many times, patients who fail to pay their credit card bill are the credit card company’s problem, not yours. In cases where you suspect fees might exceed credit card limits, you can arrange a realistic payment schedule in advance and have the patient fill out a credit application. You can find forms for this online at formswift.com, templates.office.com, and many other websites.

In some cases, it may be worth the trouble to run a background check. There are easy and affordable ways to do this. Dunn & Bradstreet, for example, will furnish a report containing payment records and details of any lawsuits, liens, and other legal actions for a nominal fee. The more financial information you have on file, the more leverage you have if a patient later balks at paying his or her balance.

For cosmetic work, always take before and after photos, and have all patients sign a written consent giving permission for the procedure, assuming full financial responsibility, and acknowledging that no guarantees have been given or implied. This defuses the common deadbeat tactics of claiming ignorance of personal financial obligations and professing dissatisfaction with the results.

Despite all your precautions, a deadbeat will inevitably slip through on occasion; but even then, you have options for extracting payment. Collection agencies are the traditional first line of attack for most medical practices. Ideally, your agency should specialize in handling medical accounts, so it will know exactly how much pressure to exert to avoid charges of harassment. Delinquent accounts should be submitted earlier rather than later to maximize the chances of success; my manager never allows an account to age more than 90 days, and if circumstances dictate, she refers them sooner than that.

When collection agencies fail, think about small claims court. You will need to learn the rules in your state, but in most states there is a small filing fee and a limit of $5,000 or so on claims. No attorneys are involved. If your paperwork is in order, the court will nearly always rule in your favor, but it will not provide the means for actual collection. In other words, you will still have to persuade the deadbeat to pay up. However, in many states a court order will give you the authority to attach a lien to property, or garnish wages, which often provides enough leverage to force payment.

What about those double-deadbeats who keep the insurance checks for themselves? First, check your third-party contract; sometimes the insurance company or HMO will be compelled to pay you directly and then go after the patient to get back its money. (They won’t volunteer this service, however – you’ll have to ask for it.)

If that’s not an option, consider reporting the misdirected payment to the Internal Revenue Service as income to the patient, by submitting a 1099 Miscellaneous Income form. Be sure to notify the deadbeat that you will be doing this. Sometimes the threat of such action will convince the individual to pay up; if not, at least you’ll have the satisfaction of knowing he or she will have to pay taxes on the money.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Since the COVID-19 pandemic began, I have received a growing number of inquiries about collection issues. For a variety of reasons, many patients seem increasingly reluctant to pay their medical bills. I’ve written many columns on keeping credit card numbers on file, and other techniques for keeping your accounts receivable in check; but despite your best efforts, there will always be a few deadbeats that you will need to pursue.

For the record, I am not speaking about patients who lost income due to the pandemic and are now struggling with debts, or otherwise have fallen on hard times and are unable to pay. I am addressing the problem of patients who are able to pay, but for whatever reason, do not.

The worst kinds of deadbeats are the ones who rob you twice; they accept payments from insurance companies and keep them. Such crooks must be pursued aggressively, with all the means at your disposal; but to reiterate the point I’ve tried to drive home repeatedly, the best cure is prevention.

You already know that you should collect as many fees as possible at the time of service. For cosmetic procedures you should require a substantial deposit in advance, with the balance due at the time of service. When that is impossible, maximize the chances you will be paid by making sure all available payment mechanisms are in place.

With my credit-card-on-file system that I’ve described many times, patients who fail to pay their credit card bill are the credit card company’s problem, not yours. In cases where you suspect fees might exceed credit card limits, you can arrange a realistic payment schedule in advance and have the patient fill out a credit application. You can find forms for this online at formswift.com, templates.office.com, and many other websites.

In some cases, it may be worth the trouble to run a background check. There are easy and affordable ways to do this. Dunn & Bradstreet, for example, will furnish a report containing payment records and details of any lawsuits, liens, and other legal actions for a nominal fee. The more financial information you have on file, the more leverage you have if a patient later balks at paying his or her balance.

For cosmetic work, always take before and after photos, and have all patients sign a written consent giving permission for the procedure, assuming full financial responsibility, and acknowledging that no guarantees have been given or implied. This defuses the common deadbeat tactics of claiming ignorance of personal financial obligations and professing dissatisfaction with the results.

Despite all your precautions, a deadbeat will inevitably slip through on occasion; but even then, you have options for extracting payment. Collection agencies are the traditional first line of attack for most medical practices. Ideally, your agency should specialize in handling medical accounts, so it will know exactly how much pressure to exert to avoid charges of harassment. Delinquent accounts should be submitted earlier rather than later to maximize the chances of success; my manager never allows an account to age more than 90 days, and if circumstances dictate, she refers them sooner than that.

When collection agencies fail, think about small claims court. You will need to learn the rules in your state, but in most states there is a small filing fee and a limit of $5,000 or so on claims. No attorneys are involved. If your paperwork is in order, the court will nearly always rule in your favor, but it will not provide the means for actual collection. In other words, you will still have to persuade the deadbeat to pay up. However, in many states a court order will give you the authority to attach a lien to property, or garnish wages, which often provides enough leverage to force payment.

What about those double-deadbeats who keep the insurance checks for themselves? First, check your third-party contract; sometimes the insurance company or HMO will be compelled to pay you directly and then go after the patient to get back its money. (They won’t volunteer this service, however – you’ll have to ask for it.)

If that’s not an option, consider reporting the misdirected payment to the Internal Revenue Service as income to the patient, by submitting a 1099 Miscellaneous Income form. Be sure to notify the deadbeat that you will be doing this. Sometimes the threat of such action will convince the individual to pay up; if not, at least you’ll have the satisfaction of knowing he or she will have to pay taxes on the money.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

A blood test that uses a patient’s unique genetic signature has shown some ability to predict nonresponse to tumor necrosis factor inhibitors as treatment for rheumatoid arthritis, an observational clinical study has found, but the test’s predictive accuracy was well below 100%.

The test is the blood-based molecular signature response classifier (MSRC) that uses RNA sequencing data based on 23 different biomarkers: 19 RNA transcripts and 4 clinical features. The clinical features are body mass index, gender, patient global assessment, and anticyclic citrullinated protein (anti-CCP) status.

The NETWORK-004 study, published in Rheumatology and Therapy, was able to stratify patients who were likely to respond inadequately to TNFi therapy and could provide patient-specific information to guide therapy choice in RA patients regardless of whether they’ve already been on TNFi therapy. The study evaluated the MSRC test in 504 patients, 391 of whom were treatment naive.
 

Avoiding ‘fail first’ approach

The idea behind the test is to circumvent the “fail first” approach in finding the right therapy for RA in an individual patient. While the test costs $4,995, Alif Saleh, chief executive officer of Scipher Medicine, which markets the test under the name PrismRA, said in a press release that it has the potential to reduce costs by $19,000 or more per patient per year by avoiding treatments that don’t work. A previous study, which Scipher funded, reported that the test resulted in savings of $7,379 in per-patient costs of ineffective therapy. The same study reported a 25% decrease in costs for ineffective treatments for Medicare-eligible patients.

The price of RA drugs, particularly anti-TNF agents, is hefty and rising. GoodRx has reported that the price of RA drugs increased 92% from 2014 to 2019, and the prices for anti-TNF agents such as etanercept and adalimumab more than doubled in that period. Adalimumab can cost upwards of $84,000 per year while etanercept has a list price of around $72,000 a year. The pharmacy benefit manager WellDyne started covering the test MSRC in February.

Nehad Soloman, MD, a rheumatologist and internist at Midwestern University Arizona College of Osteopathic Medicine in Glendale and a compensated NETWORK-004 investigator, said the MSRC test would be indicated for confirmed RA patients for whom rheumatologists are considering biologic agents, particularly TNFi drugs. “You wouldn’t do it on an RA patient who’s been on several different medications because it doesn’t serve a purpose at that point,” he said.

The potential cost savings may not be the only reason to use the test, Dr. Soloman said. “You don’t want to be dabbling with the wrong drug if there’s another path you can try and save society some money as well as the time and energy it takes to monitor the patients – as well as the patient’s pain,” he said.
 

How the MSRC test works

The MSRC test detects a signal that’s associated with a high or very high likelihood of inadequate response to TNFi therapies and indicates that the patient is unlikely to achieve low disease activity or remission with TNFi therapies. Response is defined as achieving ACR50 – meaning 50% improvement in American College of Rheumatology response criteria – at 6 months.

Test results are reported on a continuous 1-25 scale, explained Slava Akmaev, PhD, chief technology officer and head of therapeutics at Scipher. “The higher the score, the more likely the patient will have an inadequate response to TNFi therapies and be unable to reach low disease activity; the lower the score, the less likely the patient will have an inadequate response to TNFi therapies,” he said. However, Dr. Akmaev noted that a low score does not ensure a positive response to TNFi therapies.

The MSRC test differs from the multibiomarker disease activity blood test (MBDA; marketed as Vectra by Myriad Genetics) in the number of biomarkers it measures: 19 RNA transcripts vs. 12 serum protein biomarkers in MBDA. The MBDA test is also intended to provide a quantitative, objective measurement of RA disease activity rather than to predict nonresponse to TNFi or other biologics. A number of studies have validated the MBDA test for predicting disease control in RA patients, but not necessarily response to TNFi therapy.

The “high” category threshold of the MSRC test corresponds to an approximate 90% chance of inadequate response to TNFi therapy, or a 10% chance of responding. The “very high” category threshold corresponds to an approximate 95% chance of inadequate response to TNFi therapy, Dr. Akmaev said.

NETWORK-004 used area under the curve (AUC) to measure the accuracy of the MSRC test. An AUC of 1 represents 100% accuracy. Overall, the MSRC had an AUC of 0.64, or 64% accuracy of predicting patients unlikely to respond to TNFi therapy and to achieve ACR50 at 6 months, with an odds ratio of 4.1 (95% confidence interval, 2.0-8.3; P = .0001).

The predictive accuracy went up to 74% with ORs of 3.4-8.8 for additional endpoints at 3 and 6 months (P < .01). Among patients who had already been on TNFi therapy, the predictive accuracy was 83% and associated with ORs of 3.3-26.6 based on ACR, 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) metrics.

The investigators also performed an in-cohort cross-validation of the MSRC using baseline blood samples of 245 treatment-naive patients from the CERTAIN study, which yielded a 66% predictive accuracy for the ACR50 outcome at 6 months. Using the 19 RNA transcripts from the test, but not the clinical factors, the predictive accuracy was 62.5%. Using ACR70, CDAI, and DAS28 as measures for 6-month response, the cross-validation analysis of all 23 MSRC features yielded predictive accuracy of 64%-67%.

The study found significant differences in model scores between patients who did and did not have the molecular signal of nonresponse, and the proportion of patients who achieved low disease activity or remission at 6 months based on CDAI and DAS28-CRP measures was greater among those who lacked a molecular signature of nonresponse.

“Those who lack this signature can proceed with TNFi therapy and possibly achieve an increased response rate relative to the unstratified population,” wrote lead study author Stanley B. Cohen, MD, and colleagues.

Daniel E. Furst, MD, emeritus professor at the University of California, Los Angeles, described the design of the NETWORK-004 study as “excellent,” but said that it didn’t overcome potential issues with the MSRC test itself. “The results unfortunately are great for group data but not for individuals, with a predictive area under the curve of 60% to 80%, it really is not that useful,” he said. “Let’s say you’re a patient who’s not doing well, and I do a test and it’s positive; that still means that 20% of the time you will respond.”

He also noted that he coauthored a paper that used decreases in DAS28 to predict nonresponse to certolizumab pegol plus methotrexate with 95% probability in the first 12 weeks of treatment. “That’s closer to what we need,” Dr. Furst said.

However, the MSRC test is a promising sign of where testing for predicting RA therapy is headed, he said. “We are steadily working toward genetic signatures that really are predictive on an individual basis,” Dr. Furst said. “It’s coming; it’s just not here yet.”

Dr. Furst had no relevant financial relationships to disclose. Dr. Soloman is a paid investigator and consultant to Scipher Medicine.
 

Tachycardia is commonly reported in patients with post-acute COVID-19 syndrome (PACS), also known as long COVID, authors report in a new article. The researchers say tachycardia syndrome should be considered a distinct phenotype.

The study by Marcus Ståhlberg, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues was published online August 11 in The American Journal of Medicine.

Dr. Ståhlberg told this news organization that although much attention has been paid to cases of clotting and perimyocarditis in patients after COVID, relatively little attention has been paid to tachycardia, despite case reports that show that palpitations are a common complaint.

“We have diagnosed a large number of patients with postural orthostatic tachycardia syndrome [POTS] and other forms of COVID-related tachycardia at our post-COVID outpatient clinic at Karolinska University Hospital and wanted to highlight this phenomenon,” he said.

Between 25% and 50% of patients at the clinic report tachycardia and/or palpitations that last 12 weeks or longer, the authors report.

“Systematic investigations suggest that 9% of Post-acute COVID-19 syndrome patients report palpitations at six months,” the authors write.

The findings also shed light on potential tests and treatments, he said.

“Physicians should be liberal in performing a basic cardiological workup, including an ECG [electrocardiogram], echocardiography, and Holter ECG monitoring in patients complaining of palpitations and/or chest pain,” Dr. Ståhlberg said.

“If orthostatic intolerance is also reported – such as vertigo, nausea, dyspnea – suspicion of POTS should be raised and a head-up tilt test or at least an active standing test should be performed,” he said.

If POTS is confirmed, he said, patients should be offered a heart rate–lowering drug, such as low-dose propranolol or ivabradine. Compression garments, increased fluid intake, and a structured rehabilitation program also help.

“According to our clinical experience, ivabradine can also reduce symptoms in patients with inappropriate sinus tachycardia and post-COVID,” Dr. Ståhlberg said. “Another finding on Holter-ECG to look out for is frequent premature extrasystoles, which could indicate myocarditis and should warrant a cardiac MRI.”

Dr. Ståhlberg said the researchers think the mechanism underlying the tachycardia is autoimmune and that primary SARS-CoV-2 infections trigger an autoimmune response with formation of autoantibodies that can activate receptors regulating blood pressure and heart rate.

Long-lasting symptoms from COVID are prevalent, the authors note, especially in patients who experienced severe forms of the disease.

In the longest follow-up study to date of patients hospitalized with COVID, more than 60% experienced fatigue or muscle weakness 6 months after hospitalization.

PACS should not be considered a single syndrome; the term denotes an array of subsyndromes and phenotypes, the authors write. Typical symptoms include headache, fatigue, dyspnea, and mental fog but can involve multiple organs and systems.

Tachycardia can also be used as a marker to help gauge the severity of long COVID, the authors write.

“[T]achycardia can be considered a universal and easily obtainable quantitative marker of Post-acute COVID-19 syndrome and its severity rather than patient-reported symptoms, blood testing, and thoracic CT-scans,” they write.

An underrecognized complication

Erin D. Michos, MD, MHS, director of women’s cardiovascular health and associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview that she has seen many similar symptoms in the long-COVID patients referred to her practice.

Dr. Michos, who is also an associate professor of medicine and epidemiology, said she’s been receiving a “huge number” of referrals of long-COVID patients with postural tachycardia, inappropriate sinus tachycardia, and POTS.

“I think this is all in the spectrum of autonomic dysfunction that has been recognized a lot since COVID. POTS has been thought to have [a potentially] viral cause that triggers an autoimmune response. Even before COVID, many patients had POTS triggered by a viral infection. The question is whether COVID-related POTS for long COVID is different from other kinds of POTS.”

She says she treats long-COVID patients who complain of elevated heart rates with many of the cardiac workup procedures the authors list and that she treats them in a way similar to the way she treats patients with POTS.

She recommends checking resting oxygen levels and having patients walk the halls and measure their oxygen levels after walking, because their elevated heart rate may be related to ongoing lung injury from COVID.

Eric Adler, MD, a cardiologist with University of San Diego Health, told this news organization that the findings by Dr. Ståhlberg and colleagues are consistent with what he’s seeing in his clinical practice.

Dr. Adler agrees with the authors that tachycardia is an underrecognized complication of long COVID.

He said the article represents further proof that though people may survive COVID, the threat of long-term symptoms, such as heart palpitations, is real and supports the case for vaccinations.

The authors, Dr. Michos, and Dr. Adler have disclosed no relevant financial relationships.

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

Tachycardia is commonly reported in patients with post-acute COVID-19 syndrome (PACS), also known as long COVID, authors report in a new article. The researchers say tachycardia syndrome should be considered a distinct phenotype.

The study by Marcus Ståhlberg, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues was published online August 11 in The American Journal of Medicine.

Dr. Ståhlberg told this news organization that although much attention has been paid to cases of clotting and perimyocarditis in patients after COVID, relatively little attention has been paid to tachycardia, despite case reports that show that palpitations are a common complaint.

“We have diagnosed a large number of patients with postural orthostatic tachycardia syndrome [POTS] and other forms of COVID-related tachycardia at our post-COVID outpatient clinic at Karolinska University Hospital and wanted to highlight this phenomenon,” he said.

Between 25% and 50% of patients at the clinic report tachycardia and/or palpitations that last 12 weeks or longer, the authors report.

“Systematic investigations suggest that 9% of Post-acute COVID-19 syndrome patients report palpitations at six months,” the authors write.

The findings also shed light on potential tests and treatments, he said.

“Physicians should be liberal in performing a basic cardiological workup, including an ECG [electrocardiogram], echocardiography, and Holter ECG monitoring in patients complaining of palpitations and/or chest pain,” Dr. Ståhlberg said.

“If orthostatic intolerance is also reported – such as vertigo, nausea, dyspnea – suspicion of POTS should be raised and a head-up tilt test or at least an active standing test should be performed,” he said.

If POTS is confirmed, he said, patients should be offered a heart rate–lowering drug, such as low-dose propranolol or ivabradine. Compression garments, increased fluid intake, and a structured rehabilitation program also help.

“According to our clinical experience, ivabradine can also reduce symptoms in patients with inappropriate sinus tachycardia and post-COVID,” Dr. Ståhlberg said. “Another finding on Holter-ECG to look out for is frequent premature extrasystoles, which could indicate myocarditis and should warrant a cardiac MRI.”

Dr. Ståhlberg said the researchers think the mechanism underlying the tachycardia is autoimmune and that primary SARS-CoV-2 infections trigger an autoimmune response with formation of autoantibodies that can activate receptors regulating blood pressure and heart rate.

Long-lasting symptoms from COVID are prevalent, the authors note, especially in patients who experienced severe forms of the disease.

In the longest follow-up study to date of patients hospitalized with COVID, more than 60% experienced fatigue or muscle weakness 6 months after hospitalization.

PACS should not be considered a single syndrome; the term denotes an array of subsyndromes and phenotypes, the authors write. Typical symptoms include headache, fatigue, dyspnea, and mental fog but can involve multiple organs and systems.

Tachycardia can also be used as a marker to help gauge the severity of long COVID, the authors write.

“[T]achycardia can be considered a universal and easily obtainable quantitative marker of Post-acute COVID-19 syndrome and its severity rather than patient-reported symptoms, blood testing, and thoracic CT-scans,” they write.

An underrecognized complication

Erin D. Michos, MD, MHS, director of women’s cardiovascular health and associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview that she has seen many similar symptoms in the long-COVID patients referred to her practice.

Dr. Michos, who is also an associate professor of medicine and epidemiology, said she’s been receiving a “huge number” of referrals of long-COVID patients with postural tachycardia, inappropriate sinus tachycardia, and POTS.

“I think this is all in the spectrum of autonomic dysfunction that has been recognized a lot since COVID. POTS has been thought to have [a potentially] viral cause that triggers an autoimmune response. Even before COVID, many patients had POTS triggered by a viral infection. The question is whether COVID-related POTS for long COVID is different from other kinds of POTS.”

She says she treats long-COVID patients who complain of elevated heart rates with many of the cardiac workup procedures the authors list and that she treats them in a way similar to the way she treats patients with POTS.

She recommends checking resting oxygen levels and having patients walk the halls and measure their oxygen levels after walking, because their elevated heart rate may be related to ongoing lung injury from COVID.

Eric Adler, MD, a cardiologist with University of San Diego Health, told this news organization that the findings by Dr. Ståhlberg and colleagues are consistent with what he’s seeing in his clinical practice.

Dr. Adler agrees with the authors that tachycardia is an underrecognized complication of long COVID.

He said the article represents further proof that though people may survive COVID, the threat of long-term symptoms, such as heart palpitations, is real and supports the case for vaccinations.

The authors, Dr. Michos, and Dr. Adler have disclosed no relevant financial relationships.

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

Tachycardia is commonly reported in patients with post-acute COVID-19 syndrome (PACS), also known as long COVID, authors report in a new article. The researchers say tachycardia syndrome should be considered a distinct phenotype.

The study by Marcus Ståhlberg, MD, PhD, of Karolinska University Hospital, Stockholm, and colleagues was published online August 11 in The American Journal of Medicine.

Dr. Ståhlberg told this news organization that although much attention has been paid to cases of clotting and perimyocarditis in patients after COVID, relatively little attention has been paid to tachycardia, despite case reports that show that palpitations are a common complaint.

“We have diagnosed a large number of patients with postural orthostatic tachycardia syndrome [POTS] and other forms of COVID-related tachycardia at our post-COVID outpatient clinic at Karolinska University Hospital and wanted to highlight this phenomenon,” he said.

Between 25% and 50% of patients at the clinic report tachycardia and/or palpitations that last 12 weeks or longer, the authors report.

“Systematic investigations suggest that 9% of Post-acute COVID-19 syndrome patients report palpitations at six months,” the authors write.

The findings also shed light on potential tests and treatments, he said.

“Physicians should be liberal in performing a basic cardiological workup, including an ECG [electrocardiogram], echocardiography, and Holter ECG monitoring in patients complaining of palpitations and/or chest pain,” Dr. Ståhlberg said.

“If orthostatic intolerance is also reported – such as vertigo, nausea, dyspnea – suspicion of POTS should be raised and a head-up tilt test or at least an active standing test should be performed,” he said.

If POTS is confirmed, he said, patients should be offered a heart rate–lowering drug, such as low-dose propranolol or ivabradine. Compression garments, increased fluid intake, and a structured rehabilitation program also help.

“According to our clinical experience, ivabradine can also reduce symptoms in patients with inappropriate sinus tachycardia and post-COVID,” Dr. Ståhlberg said. “Another finding on Holter-ECG to look out for is frequent premature extrasystoles, which could indicate myocarditis and should warrant a cardiac MRI.”

Dr. Ståhlberg said the researchers think the mechanism underlying the tachycardia is autoimmune and that primary SARS-CoV-2 infections trigger an autoimmune response with formation of autoantibodies that can activate receptors regulating blood pressure and heart rate.

Long-lasting symptoms from COVID are prevalent, the authors note, especially in patients who experienced severe forms of the disease.

In the longest follow-up study to date of patients hospitalized with COVID, more than 60% experienced fatigue or muscle weakness 6 months after hospitalization.

PACS should not be considered a single syndrome; the term denotes an array of subsyndromes and phenotypes, the authors write. Typical symptoms include headache, fatigue, dyspnea, and mental fog but can involve multiple organs and systems.

Tachycardia can also be used as a marker to help gauge the severity of long COVID, the authors write.

“[T]achycardia can be considered a universal and easily obtainable quantitative marker of Post-acute COVID-19 syndrome and its severity rather than patient-reported symptoms, blood testing, and thoracic CT-scans,” they write.

An underrecognized complication

Erin D. Michos, MD, MHS, director of women’s cardiovascular health and associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview that she has seen many similar symptoms in the long-COVID patients referred to her practice.

Dr. Michos, who is also an associate professor of medicine and epidemiology, said she’s been receiving a “huge number” of referrals of long-COVID patients with postural tachycardia, inappropriate sinus tachycardia, and POTS.

“I think this is all in the spectrum of autonomic dysfunction that has been recognized a lot since COVID. POTS has been thought to have [a potentially] viral cause that triggers an autoimmune response. Even before COVID, many patients had POTS triggered by a viral infection. The question is whether COVID-related POTS for long COVID is different from other kinds of POTS.”

She says she treats long-COVID patients who complain of elevated heart rates with many of the cardiac workup procedures the authors list and that she treats them in a way similar to the way she treats patients with POTS.

She recommends checking resting oxygen levels and having patients walk the halls and measure their oxygen levels after walking, because their elevated heart rate may be related to ongoing lung injury from COVID.

Eric Adler, MD, a cardiologist with University of San Diego Health, told this news organization that the findings by Dr. Ståhlberg and colleagues are consistent with what he’s seeing in his clinical practice.

Dr. Adler agrees with the authors that tachycardia is an underrecognized complication of long COVID.

He said the article represents further proof that though people may survive COVID, the threat of long-term symptoms, such as heart palpitations, is real and supports the case for vaccinations.

The authors, Dr. Michos, and Dr. Adler have disclosed no relevant financial relationships.

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