Hematology News

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.

In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.

The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
 

Throat swab alone less effective

Using a throat swab alone was less effective and missed more cases than the other methods, she said.

The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.

A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.

She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.

Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.

Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
 

Rapid testing vs. standard

Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.

The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.

The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted. 

Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”

But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.

Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.

And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.

“You will miss a certain percentage of people using this rapid isothermal test,” she said.

However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”

On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”

The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.

Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
 

Testing the immunocompromised

Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.

Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.

But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
 

Home testing

The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.

Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.

“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.

The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.

Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”

Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.

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

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Individuals with nonsevere hemophilia A (NSHA) in the United States showed increased mortality based upon increasing age, male sex, and infections, according to the results of a large database analysis.

However, even though inhibitors, which can develop from factor VIII (FVIII) hemophilia therapy, were detected at an earlier age than previously reported, their presence was not associated with an increased risk of mortality according to the report published in Blood Advances (2020;4[19]:4739-47).

The researchers assessed 6,624 individuals born between 1920 and 2018 (5,694 [86.0%] men and 930 women) with NSHA from the ATHNdataset, according to Ming Y. Lim, MBBCH, MS, of the division of hematology and hematologic malignancies, University of Utah, Salt Lake City, and colleagues.

Demographically, the proportion of Black participants in the ATHNdataset was lower at 8.2%, than the 11.6% found in U.S. hemophilia population as a whole. A total of 77.3% (n = 5,122) had documented exposure to FVIII concentrates, 8.4% (n = 555) had no documented exposure, and information was unknown for the remaining 14.3%.
 

Causes of mortality

The researchers found that inhibitors occurred at an early age of 13 years with a prevalence of 2.6%, compared with the commonly reported median age of about 30 years for inhibitor development, but their presence was not associated with an increased risk of mortality, according to the authors. Instead, they found that mortality rates in the NSHA cohort were influenced by age, male sex, and hepatitis C and HIV infections.

The researchers speculated that the earlier age of inhibitor development may be due to the fact of the increased availability of FVIII concentrates over time, and that they may have been used more often from 2010 to 2018, compared with previously reported INSIGHT study (1980-2011).

In a multivariable analysis, men with NSHA were found to have 2.6 times the risk of death. Mortality risk increased twofold with each additional decade of age. Persons with hepatitis C had twice the risk of death and persons with HIV had almost four times the risk, compared with persons without these conditions.

The most common primary cause of death was malignancy (20.0%). The observed number of deaths from liver disease in the NSHA cohort was almost five times the expected death rate at 14%. Hemophilia-related deaths were 5.9%.

“Continued monitoring of persons with NSHA by comprehensive care visits at HTC should occur annually to address hemophilia-related issues and other age-related comorbidities, in collaboration with the primary care physician and other subspecialists. Importantly, we found that in the NSHA cohort, the development of inhibitors occurred at an earlier age than previously reported. This highlights the importance of routine monitoring for inhibitors in the NSHA population, regardless of age, especially if they have recently received intense factor replacement therapy,” the researchers concluded.

Ms. Lim reported no conflicts. Other authors reported research and consulting funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Lim MY et al. Blood Adv. 2020;4(19):4739-47.

Individuals with nonsevere hemophilia A (NSHA) in the United States showed increased mortality based upon increasing age, male sex, and infections, according to the results of a large database analysis.

However, even though inhibitors, which can develop from factor VIII (FVIII) hemophilia therapy, were detected at an earlier age than previously reported, their presence was not associated with an increased risk of mortality according to the report published in Blood Advances (2020;4[19]:4739-47).

The researchers assessed 6,624 individuals born between 1920 and 2018 (5,694 [86.0%] men and 930 women) with NSHA from the ATHNdataset, according to Ming Y. Lim, MBBCH, MS, of the division of hematology and hematologic malignancies, University of Utah, Salt Lake City, and colleagues.

Demographically, the proportion of Black participants in the ATHNdataset was lower at 8.2%, than the 11.6% found in U.S. hemophilia population as a whole. A total of 77.3% (n = 5,122) had documented exposure to FVIII concentrates, 8.4% (n = 555) had no documented exposure, and information was unknown for the remaining 14.3%.
 

Causes of mortality

The researchers found that inhibitors occurred at an early age of 13 years with a prevalence of 2.6%, compared with the commonly reported median age of about 30 years for inhibitor development, but their presence was not associated with an increased risk of mortality, according to the authors. Instead, they found that mortality rates in the NSHA cohort were influenced by age, male sex, and hepatitis C and HIV infections.

The researchers speculated that the earlier age of inhibitor development may be due to the fact of the increased availability of FVIII concentrates over time, and that they may have been used more often from 2010 to 2018, compared with previously reported INSIGHT study (1980-2011).

In a multivariable analysis, men with NSHA were found to have 2.6 times the risk of death. Mortality risk increased twofold with each additional decade of age. Persons with hepatitis C had twice the risk of death and persons with HIV had almost four times the risk, compared with persons without these conditions.

The most common primary cause of death was malignancy (20.0%). The observed number of deaths from liver disease in the NSHA cohort was almost five times the expected death rate at 14%. Hemophilia-related deaths were 5.9%.

“Continued monitoring of persons with NSHA by comprehensive care visits at HTC should occur annually to address hemophilia-related issues and other age-related comorbidities, in collaboration with the primary care physician and other subspecialists. Importantly, we found that in the NSHA cohort, the development of inhibitors occurred at an earlier age than previously reported. This highlights the importance of routine monitoring for inhibitors in the NSHA population, regardless of age, especially if they have recently received intense factor replacement therapy,” the researchers concluded.

Ms. Lim reported no conflicts. Other authors reported research and consulting funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Lim MY et al. Blood Adv. 2020;4(19):4739-47.

Individuals with nonsevere hemophilia A (NSHA) in the United States showed increased mortality based upon increasing age, male sex, and infections, according to the results of a large database analysis.

However, even though inhibitors, which can develop from factor VIII (FVIII) hemophilia therapy, were detected at an earlier age than previously reported, their presence was not associated with an increased risk of mortality according to the report published in Blood Advances (2020;4[19]:4739-47).

The researchers assessed 6,624 individuals born between 1920 and 2018 (5,694 [86.0%] men and 930 women) with NSHA from the ATHNdataset, according to Ming Y. Lim, MBBCH, MS, of the division of hematology and hematologic malignancies, University of Utah, Salt Lake City, and colleagues.

Demographically, the proportion of Black participants in the ATHNdataset was lower at 8.2%, than the 11.6% found in U.S. hemophilia population as a whole. A total of 77.3% (n = 5,122) had documented exposure to FVIII concentrates, 8.4% (n = 555) had no documented exposure, and information was unknown for the remaining 14.3%.
 

Causes of mortality

The researchers found that inhibitors occurred at an early age of 13 years with a prevalence of 2.6%, compared with the commonly reported median age of about 30 years for inhibitor development, but their presence was not associated with an increased risk of mortality, according to the authors. Instead, they found that mortality rates in the NSHA cohort were influenced by age, male sex, and hepatitis C and HIV infections.

The researchers speculated that the earlier age of inhibitor development may be due to the fact of the increased availability of FVIII concentrates over time, and that they may have been used more often from 2010 to 2018, compared with previously reported INSIGHT study (1980-2011).

In a multivariable analysis, men with NSHA were found to have 2.6 times the risk of death. Mortality risk increased twofold with each additional decade of age. Persons with hepatitis C had twice the risk of death and persons with HIV had almost four times the risk, compared with persons without these conditions.

The most common primary cause of death was malignancy (20.0%). The observed number of deaths from liver disease in the NSHA cohort was almost five times the expected death rate at 14%. Hemophilia-related deaths were 5.9%.

“Continued monitoring of persons with NSHA by comprehensive care visits at HTC should occur annually to address hemophilia-related issues and other age-related comorbidities, in collaboration with the primary care physician and other subspecialists. Importantly, we found that in the NSHA cohort, the development of inhibitors occurred at an earlier age than previously reported. This highlights the importance of routine monitoring for inhibitors in the NSHA population, regardless of age, especially if they have recently received intense factor replacement therapy,” the researchers concluded.

Ms. Lim reported no conflicts. Other authors reported research and consulting funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Lim MY et al. Blood Adv. 2020;4(19):4739-47.

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

Nearly 10 months since the onset of the COVID-19 pandemic in the United States, ICUs across the country are reaching maximum capacity and hospitalizations are outnumbering the available providers and staff to care for them. Clinicians everywhere are becoming exhausted and frustrated, and the world is all asking when an end to this pandemic will be in sight? The Food and Drug Administration issued emergency authorization for two multidose COVID-19 vaccines that are now being deployed across the country.

At this writing, 2.8 million Americans have received their first COVID-19 vaccine dose, a number far short of the projected 100 million. The limited production capacity and tiered distribution are the main determinants of who gets the vaccine and when, but a third and extremely important factor in whether people will choose to get vaccinated is their level of awareness of and trust in the scientific and medical processes behind wide-scale vaccination.

As medical professionals, many of us wouldn’t hesitate to get vaccinated against a pandemic virus. Concerns about safety and the integrity of the COVID-19 vaccine development process in light of the “warp speed” of its production has many Americans concerned about getting vaccinated. We may not be able to relate to some patients’ reluctance to receive a vaccine that has been confirmed by phase 3 clinical trials with collectively over 66,000 participants (nearly 10% African American in each study) to have an effectiveness of over 90%. We are so intimately familiar with the vaccine development process, the medical terminology used to describe these results and the effectiveness of vaccines overall in eliminating infectious diseases like polio and smallpox. To many of us, receiving the COVID-19 vaccine may be considered a no-brainer. However, and especially for BIPOC (Black, Indigenous, and people of color) patients with sickle cell disease or other hematologic disorders, the history of medical racism and a pattern of negative health care experiences have sown a distrust of the medical research community that spurs vaccine hesitancy despite the far-reaching impact of this pandemic.

I asked an African American friend of mine who is a pediatrician if she would get the vaccine, to which she replied: “People of color are already aware of the experiments and trials performed on our communities without the knowledge and informed consent of those being tested – many of whom were children, impoverished or disenfranchised – so while I personally will get vaccinated, I understand why some wouldn’t be as trusting.”

In December 2020, a poll by the Kaiser Family Foundation found that a primary factor behind COVID-19 vaccine hesitancy among Black respondents was the fear of catching the virus from the vaccine.¹ While this is an understandable concern for the general public, there needs to be a wide-reaching patient education effort to teach about the vaccine and how it was designed to work, (especially around the use of messenger RNA technology) so as to put such fears to rest and empower patients to go into this process as knowledgeable advocates for their own health.

With so many sources of information about the pandemic, there are just as many sources of misinformation being spouted by biased outlets on all sides of the political spectrum.

Physicians are most likely to influence their patients’ willingness to take the flu vaccine, accept treatment recommendations as well as potentially accept the COVID-19 vaccine. Our responsibility as care providers is to help our patients filter through the information and provide them with the tools, they need to understand what is fact and what is fiction. We are to answer their questions and concerns, correct any misunderstandings, and address their individual reasons for hesitancy. We must also pay particular attention to our BIPOC patient populations who may have unique reasons for declining the vaccine, compared with the general population. Our conversations should not only reassure patients that the vaccines currently available won’t give them COVID-19, but also address concerns about the efficacy and safety of the vaccine and reiterate that no corners were cut in the development and approval process.

As a hematologist I have had to become very comfortable with having uncomfortable conversations with my patients about the history of maltreatment and discrimination toward minorities in health care, while reassuring them of the current attempts to right those wrongs and the major wins we have had in research when it comes to adapting therapeutics to diverse populations for optimal outcomes.

The conversation about vaccine hesitancy should be held with patience and humility, acknowledging the past and validating patient concerns that will influence their decisions. We need to be more humane and relatable, and use real-world language to clearly share the facts without buzzwords and jargon that may confuse or even reinforce perceptions of lack of transparency.

I received my COVID-19 vaccine on Dec. 29, 2020, and my experience was similar to that of anyone else’s. I had the same concerns most of my patients and colleagues have expressed, but when I saw my sister share her “postvax selfie” on WhatsApp and discussed her experience with her, I felt more comfortable. I then spoke with my allergist, my primary care provider, my husband, and other people in my personal circles before I scheduled my appointment. After my first dose, I called my sister-in-law, a nurse in Canada, who expressed the same concerns that I had and was about to cancel her appointment for that afternoon. I shared my selfie, I shared my experience, and that afternoon she got her vaccine.

The best way to restore a fundamental trust in science and medicine in our patients is to relate to them as humans. Our patients need to know we have the same concerns and fears that they do and that sometimes we have just as many questions too. Communicating openly and authentically, not only with our patients but in all our spheres of influence, can help rebuild the relationship between the public and the health care system. By giving them a glimpse of our humanity, we can support each other as we hopefully eventually see an end to this pandemic.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

References

1. www.kff.org/coronavirus-covid-19/report/kff-covid-19-vaccine-monitor-december-2020/

Nearly 10 months since the onset of the COVID-19 pandemic in the United States, ICUs across the country are reaching maximum capacity and hospitalizations are outnumbering the available providers and staff to care for them. Clinicians everywhere are becoming exhausted and frustrated, and the world is all asking when an end to this pandemic will be in sight? The Food and Drug Administration issued emergency authorization for two multidose COVID-19 vaccines that are now being deployed across the country.

At this writing, 2.8 million Americans have received their first COVID-19 vaccine dose, a number far short of the projected 100 million. The limited production capacity and tiered distribution are the main determinants of who gets the vaccine and when, but a third and extremely important factor in whether people will choose to get vaccinated is their level of awareness of and trust in the scientific and medical processes behind wide-scale vaccination.

As medical professionals, many of us wouldn’t hesitate to get vaccinated against a pandemic virus. Concerns about safety and the integrity of the COVID-19 vaccine development process in light of the “warp speed” of its production has many Americans concerned about getting vaccinated. We may not be able to relate to some patients’ reluctance to receive a vaccine that has been confirmed by phase 3 clinical trials with collectively over 66,000 participants (nearly 10% African American in each study) to have an effectiveness of over 90%. We are so intimately familiar with the vaccine development process, the medical terminology used to describe these results and the effectiveness of vaccines overall in eliminating infectious diseases like polio and smallpox. To many of us, receiving the COVID-19 vaccine may be considered a no-brainer. However, and especially for BIPOC (Black, Indigenous, and people of color) patients with sickle cell disease or other hematologic disorders, the history of medical racism and a pattern of negative health care experiences have sown a distrust of the medical research community that spurs vaccine hesitancy despite the far-reaching impact of this pandemic.

I asked an African American friend of mine who is a pediatrician if she would get the vaccine, to which she replied: “People of color are already aware of the experiments and trials performed on our communities without the knowledge and informed consent of those being tested – many of whom were children, impoverished or disenfranchised – so while I personally will get vaccinated, I understand why some wouldn’t be as trusting.”

In December 2020, a poll by the Kaiser Family Foundation found that a primary factor behind COVID-19 vaccine hesitancy among Black respondents was the fear of catching the virus from the vaccine.¹ While this is an understandable concern for the general public, there needs to be a wide-reaching patient education effort to teach about the vaccine and how it was designed to work, (especially around the use of messenger RNA technology) so as to put such fears to rest and empower patients to go into this process as knowledgeable advocates for their own health.

With so many sources of information about the pandemic, there are just as many sources of misinformation being spouted by biased outlets on all sides of the political spectrum.

Physicians are most likely to influence their patients’ willingness to take the flu vaccine, accept treatment recommendations as well as potentially accept the COVID-19 vaccine. Our responsibility as care providers is to help our patients filter through the information and provide them with the tools, they need to understand what is fact and what is fiction. We are to answer their questions and concerns, correct any misunderstandings, and address their individual reasons for hesitancy. We must also pay particular attention to our BIPOC patient populations who may have unique reasons for declining the vaccine, compared with the general population. Our conversations should not only reassure patients that the vaccines currently available won’t give them COVID-19, but also address concerns about the efficacy and safety of the vaccine and reiterate that no corners were cut in the development and approval process.

As a hematologist I have had to become very comfortable with having uncomfortable conversations with my patients about the history of maltreatment and discrimination toward minorities in health care, while reassuring them of the current attempts to right those wrongs and the major wins we have had in research when it comes to adapting therapeutics to diverse populations for optimal outcomes.

The conversation about vaccine hesitancy should be held with patience and humility, acknowledging the past and validating patient concerns that will influence their decisions. We need to be more humane and relatable, and use real-world language to clearly share the facts without buzzwords and jargon that may confuse or even reinforce perceptions of lack of transparency.

I received my COVID-19 vaccine on Dec. 29, 2020, and my experience was similar to that of anyone else’s. I had the same concerns most of my patients and colleagues have expressed, but when I saw my sister share her “postvax selfie” on WhatsApp and discussed her experience with her, I felt more comfortable. I then spoke with my allergist, my primary care provider, my husband, and other people in my personal circles before I scheduled my appointment. After my first dose, I called my sister-in-law, a nurse in Canada, who expressed the same concerns that I had and was about to cancel her appointment for that afternoon. I shared my selfie, I shared my experience, and that afternoon she got her vaccine.

The best way to restore a fundamental trust in science and medicine in our patients is to relate to them as humans. Our patients need to know we have the same concerns and fears that they do and that sometimes we have just as many questions too. Communicating openly and authentically, not only with our patients but in all our spheres of influence, can help rebuild the relationship between the public and the health care system. By giving them a glimpse of our humanity, we can support each other as we hopefully eventually see an end to this pandemic.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

References

1. www.kff.org/coronavirus-covid-19/report/kff-covid-19-vaccine-monitor-december-2020/

Nearly 10 months since the onset of the COVID-19 pandemic in the United States, ICUs across the country are reaching maximum capacity and hospitalizations are outnumbering the available providers and staff to care for them. Clinicians everywhere are becoming exhausted and frustrated, and the world is all asking when an end to this pandemic will be in sight? The Food and Drug Administration issued emergency authorization for two multidose COVID-19 vaccines that are now being deployed across the country.

At this writing, 2.8 million Americans have received their first COVID-19 vaccine dose, a number far short of the projected 100 million. The limited production capacity and tiered distribution are the main determinants of who gets the vaccine and when, but a third and extremely important factor in whether people will choose to get vaccinated is their level of awareness of and trust in the scientific and medical processes behind wide-scale vaccination.

As medical professionals, many of us wouldn’t hesitate to get vaccinated against a pandemic virus. Concerns about safety and the integrity of the COVID-19 vaccine development process in light of the “warp speed” of its production has many Americans concerned about getting vaccinated. We may not be able to relate to some patients’ reluctance to receive a vaccine that has been confirmed by phase 3 clinical trials with collectively over 66,000 participants (nearly 10% African American in each study) to have an effectiveness of over 90%. We are so intimately familiar with the vaccine development process, the medical terminology used to describe these results and the effectiveness of vaccines overall in eliminating infectious diseases like polio and smallpox. To many of us, receiving the COVID-19 vaccine may be considered a no-brainer. However, and especially for BIPOC (Black, Indigenous, and people of color) patients with sickle cell disease or other hematologic disorders, the history of medical racism and a pattern of negative health care experiences have sown a distrust of the medical research community that spurs vaccine hesitancy despite the far-reaching impact of this pandemic.

I asked an African American friend of mine who is a pediatrician if she would get the vaccine, to which she replied: “People of color are already aware of the experiments and trials performed on our communities without the knowledge and informed consent of those being tested – many of whom were children, impoverished or disenfranchised – so while I personally will get vaccinated, I understand why some wouldn’t be as trusting.”

In December 2020, a poll by the Kaiser Family Foundation found that a primary factor behind COVID-19 vaccine hesitancy among Black respondents was the fear of catching the virus from the vaccine.¹ While this is an understandable concern for the general public, there needs to be a wide-reaching patient education effort to teach about the vaccine and how it was designed to work, (especially around the use of messenger RNA technology) so as to put such fears to rest and empower patients to go into this process as knowledgeable advocates for their own health.

With so many sources of information about the pandemic, there are just as many sources of misinformation being spouted by biased outlets on all sides of the political spectrum.

Physicians are most likely to influence their patients’ willingness to take the flu vaccine, accept treatment recommendations as well as potentially accept the COVID-19 vaccine. Our responsibility as care providers is to help our patients filter through the information and provide them with the tools, they need to understand what is fact and what is fiction. We are to answer their questions and concerns, correct any misunderstandings, and address their individual reasons for hesitancy. We must also pay particular attention to our BIPOC patient populations who may have unique reasons for declining the vaccine, compared with the general population. Our conversations should not only reassure patients that the vaccines currently available won’t give them COVID-19, but also address concerns about the efficacy and safety of the vaccine and reiterate that no corners were cut in the development and approval process.

As a hematologist I have had to become very comfortable with having uncomfortable conversations with my patients about the history of maltreatment and discrimination toward minorities in health care, while reassuring them of the current attempts to right those wrongs and the major wins we have had in research when it comes to adapting therapeutics to diverse populations for optimal outcomes.

The conversation about vaccine hesitancy should be held with patience and humility, acknowledging the past and validating patient concerns that will influence their decisions. We need to be more humane and relatable, and use real-world language to clearly share the facts without buzzwords and jargon that may confuse or even reinforce perceptions of lack of transparency.

I received my COVID-19 vaccine on Dec. 29, 2020, and my experience was similar to that of anyone else’s. I had the same concerns most of my patients and colleagues have expressed, but when I saw my sister share her “postvax selfie” on WhatsApp and discussed her experience with her, I felt more comfortable. I then spoke with my allergist, my primary care provider, my husband, and other people in my personal circles before I scheduled my appointment. After my first dose, I called my sister-in-law, a nurse in Canada, who expressed the same concerns that I had and was about to cancel her appointment for that afternoon. I shared my selfie, I shared my experience, and that afternoon she got her vaccine.

The best way to restore a fundamental trust in science and medicine in our patients is to relate to them as humans. Our patients need to know we have the same concerns and fears that they do and that sometimes we have just as many questions too. Communicating openly and authentically, not only with our patients but in all our spheres of influence, can help rebuild the relationship between the public and the health care system. By giving them a glimpse of our humanity, we can support each other as we hopefully eventually see an end to this pandemic.

Ifeyinwa (Ify) Osunkwo, MD, MPH, is a professor of medicine and the director of the Sickle Cell Disease Enterprise at the Levine Cancer Institute, Atrium Health, Charlotte, N.C. She is the editor in chief of Hematology News.

References

1. www.kff.org/coronavirus-covid-19/report/kff-covid-19-vaccine-monitor-december-2020/