Infectious Disease Practitioner

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

The percentage of physicians in the United States who are Black has increased only 4% in the past 120 years, and the number of Black male doctors has not changed at all since 1940, according to a new study.

In 1900, 1.3% of physicians were Black. In 1940, 2.8% of physicians were Black, and by 2018 – when almost 13% of the population was Black – 5.4% of doctors were Black, reports Dan Ly, MD, PhD, MPP, an assistant professor of medicine at the University of California, Los Angeles, in a study published online April 19, 2021, in the Journal of General Internal Medicine.

The proportion of male Black physicians was 2.7% in 1940 and 2.6% in 2018.

Dr. Ly also found a significant wage gap. The median income earned by White doctors was $50,000 more than the median income of Black physicians in 2018. Dr. Ly based his findings on the U.S. Census Decennial Census long form, accessed via IPUMS, a free database funded by the National Institutes of Health and other organizations.

“If we care about the health of the population, particularly the health of Black patients, we should care about how small the proportion of our physicians who are Black is and the extremely slow progress we have made as a medical system in increasing that proportion,” Dr. Ly said in an interview.

Dr. Ly said he took on this research in part because previous studies have shown that Black patients are more likely to seek preventive care from Black doctors. Thus, increasing the numbers of Black physicians could narrow gaps in life expectancy between Whites and Blacks.

He also wanted to see whether progress had been made as a result of various medical organizations and the Association of American Medical Colleges undertaking initiatives to increase workforce diversity. There has been “very, very little” progress, he said.

Norma Poll-Hunter, PhD, the AAMC’s senior director of workforce diversity, said Dr. Ly’s report “was not surprising at all.”

The AAMC reported in 2014 that the number of Black men who apply to and matriculate into medical schools has been declining since 1978. That year, there were 1,410 Black male applicants and 542 Black enrollees. In 2014, there were 1,337 applicants and 515 enrollees.

Since 2014, Black male enrollment has increased slightly, rising from 2.4% in the 2014-2015 school year to 2.9% in the 2019-2020 year, the AAMC reported last year.

In addition, among other historically underrepresented minorities, “we really have seen very small progress” despite the increase in the number of medical schools, Dr. Poll-Hunter said in an interview.

The AAMC and the National Medical Association consider the lack of Black male applicants and matriculants to be a national crisis. The two groups started an alliance in 2020 aimed at finding ways to amplify and support Black men’s interest in medicine and the biomedical sciences and to “develop systems-based solutions to address exclusionary practices that create barriers for Black men and prevent them from having equitable opportunities to successfully enroll in medical school.”

Solutions include requiring medical school admissions committees and application screeners to undergo implicit bias awareness and mitigation training, adopting holistic admissions reviews, and incentivizing institutions of higher learning to partner with Black communities in urban and rural school systems to establish K-12 health sciences academies, said NMA President Leon McDougle, MD, MPH.

“There are the systems factors, and racism is a big one that we have to tackle,” said Dr. Poll-Hunter.

Diversity isn’t just about numbers, said Dr. McDougle, a professor of family medicine and associate dean for diversity and inclusion at Ohio State University, Columbus. “We know that medical school graduates who are African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native are more likely to serve those communities as practicing physicians.

“The COVID-19 pandemic highlighted the urgent need for more African American or Black, Hispanic or Latinx, or American Indian or Alaskan Native physicians,” he said. “Inadequate access to culturally competent care has exacerbated existing health disparities, resulting in death and hospitalization rates up to three to four times the rates of European American or White people.”

Dr. Poll-Hunter also said that studies have shown that diversity in the classroom creates a more enriched learning environment and increases civic mindedness and cognitive complexity, “as well as helps us understand people who are different than ourselves.”

The diversity goal “is not about quotas, it’s about excellence,” she said. “We know that there’s talent that exists, and we want to make sure that everyone has an opportunity to be successful.”

Dr. Ly has disclosed no relevant financial relationships.

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

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

Do your patients think that getting COVID-19 is fully protective against subsequent reinfection? Tell it to the Marines.

A study of U.S. Marine recruits on their way to boot camp at Parris Island, S.C., showed that those who were seropositive at baseline, indicating prior exposure to SARS-CoV-2, remained at some risk for reinfection. They had about one-fifth the risk of subsequent infection, compared with seronegative recruits during basic training, but reinfections did occur.

The study, by Stuart C. Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York, and colleagues, was published in The Lancet Respiratory Medicine.

“Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection,” they wrote.

An infectious disease specialist who was not involved in the study said that the findings provide further evidence about the level of immunity acquired after an infection.

“It’s quite clear that reinfections do occur, they are of public health importance, and they’re something we need to be mindful of in terms of advising patients about whether a prior infection protects them from reinfection,” Mark Siedner, MD, MPH, a clinician and researcher in the division of infectious diseases at Massachusetts General Hospital, Boston, said in an interview.

The study results reinforce that “not all antibodies are the same,” said Sachin Gupta, MD, an attending physician in pulmonary and critical care medicine at Alameda Health System in Oakland, Calif. “We’re seeing still that 10% of folks who have antibodies can get infected again,” he said in an interview.

CHARM initiative

Dr. Sealfon and colleagues presented an analysis of data from the ironically named CHARM (COVID-19 Health Action Response for Marines) prospective study.

CHARM included U.S. Marine recruits, most of them male, aged 18-20 years, who were instructed to follow a 2-week unsupervised quarantine at home, after which they reported to a Marine-supervised facility for an additional 2-week quarantine.

At baseline, participants were tested for SARS-CoV-2 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (ELISA).

The recruits filled out questionnaires asking them to report any of 14 specific COVID-19–related symptoms or any other unspecified symptom, as well as demographic information, risk factors, and a brief medical history.

Investigators tested recruits for SARS-CoV-2 infection by polymerase chain reaction (PCR) assay at weeks 0, 1, and 2 of quarantine, and any who had positive PCR results during quarantine were excluded.

Participants who had three negative swab PCR results during quarantine and a baseline serology test at the beginning of the supervised quarantine period – either seronegative or seropositive – then went on to enjoy their basic training at the Marine Corps Recruit Depot, Parris Island, S.C.

The participants were followed prospectively with PCR tests at weeks 2, 4, and 6 in both the seropositive and seronegative groups, and sera were obtained at the same time.
 

Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.
 

Lessons

Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.

COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.

Floaria Bicher/iStock/Getty Images Plus

“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.

The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.

“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.

The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.

The initial findings from the registry were published online in the Journal of the American College of Cardiology.
 

Atypical symptoms may explain high death rate

The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls). 

This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.

The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.

These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.

The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.

COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.

Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).

The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.

Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.

“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.  

“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.

Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.

Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.

This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.

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

COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.

Floaria Bicher/iStock/Getty Images Plus

“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.

The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.

“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.

The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.

The initial findings from the registry were published online in the Journal of the American College of Cardiology.
 

Atypical symptoms may explain high death rate

The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls). 

This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.

The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.

These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.

The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.

COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.

Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).

The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.

Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.

“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.  

“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.

Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.

Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.

This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.

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

COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.

Floaria Bicher/iStock/Getty Images Plus

“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.

The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.

“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.

The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.

The initial findings from the registry were published online in the Journal of the American College of Cardiology.
 

Atypical symptoms may explain high death rate

The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls). 

This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.

The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.

These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.

The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.

COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.

Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).

The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.

Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.

“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.  

“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.

Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.

Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.

This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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

Long-haul neurologic symptoms of COVID-19 seem to be distinct from neurologic conditions found in acute disease. Among the patient population of long-haulers complaining of brain fog, muscular ache, and other issues, many had mild COVID-19. Much work remains to be done to understand the biological mechanisms behind these problems, but inflammation and autoimmune responses may play a role in some cases.

Those were some of the takeaways from a talk by Serena Spudich, MD, who presented her research at the 2021 annual meeting of the American Academy of Neurology. Dr. Spudich is the division chief of neurologic infections and global neurology and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
 

Examining the nervous system’s involvement in COVID-19

Even early on in the pandemic, it became clear that there were lingering complaints of neuromuscular problems, cognitive dysfunction, and mood and psychiatric issues. Breathing and heart rate problems also can arise. “There seems to be a preponderance of syndromes that reflect involvement of the nervous system,” said Dr. Spudich.

To try to understand the etiology of these persistent problems, Dr. Spudich said it’s important to examine the nervous system’s involvement in acute COVID-19. She has been involved in these efforts since early in the pandemic, when she ran an inpatient consult service at Yale dedicated to neurologic effects of acute COVID-19. She witnessed complications including stroke, encephalopathy, and seizures, among others.

Stroke during acute COVID-19 seemed to be associated with inflammation and endothelial activation or endotheliopathy. SARS-CoV-2 has been undetectable in the cerebrospinal fluid (CSF) of patients with acute COVID-19 and neurologic symptoms, but inflammatory cytokines can be present along with increased frequency of B cells. Anti–SARS-CoV-2 antibodies have also been found in CSF, some of which were auto reactive to brain tissue. The immune response was altered, compared with healthy controls, and in the CNS, compared with in the blood, “raising the question of whether inflammation and autoimmunity may be underlying causes of these syndromes,” said Dr. Spudich.

She also pointed to an MRI study of autopsied brain tissue of patients with COVID-19 and neurologic complications, which showed indications of both hemorrhagic and ischemic microvascular injury. “It’s just a reminder that, during acute COVID-19, there may be inflammation in the brain, there may be autoimmune reactions, and there may be vascular changes that underlie some of the neurologic syndromes that are seen,” said Dr. Spudich.
 

A panoply of different syndromes

In October, Yale set up a post-COVID neurologic clinic that brought together pulmonary, cardiology, and psychiatric specialists, many of whom saw the same patients, about 60% of whom had cognitive impairment, more than 40% had neuromuscular problems, and over 30% headache. “There’s not a single entity of a post-COVID neurologic syndrome. There’s a panoply of different syndromes that may have similar or distinct etiologies,” said Dr. Spudich.

Most patients were in their 30s, 40s, or 50s. That doesn’t necessarily mean this is the most common age range for these issues, though. There could be some bias if these individuals are seeking specialty care because they expected to recover from COVID-19 quickly. But it could be that there is something biologically unique among this age group that predisposes them to complications. Regardless, two out of three patients were never hospitalized, “suggesting that even mild COVID-19 can lead to some long-term sequelae,” said Dr. Spudich.

One potential explanation for long-term neurologic syndromes is that they are an extension of the inflammation, autoimmunity, and immune perturbation occurring during acute disease. One study looked at 18 cancer patients who had neurologic complications with COVID-19. Two months after onset, they had elevated markers of neuroinflammation and neuronal injury in the cerebral spinal fluid compared to cancer patients with no history of COVID-19.
 

Looking for biologic markers

An Italian study looked at patients who were evaluated during acute hospitalization and again 3 months later, and found that some markers of inflation in the blood were associated with later cognitive impairment. The patients were more severely ill, so it’s not clear what the findings mean for patients who present with neurologic symptoms after milder illness.

A PET scan study of 35 patients with persistent neurologic symptoms found patterns of reduced fluorodeoxyglucose uptake in some regions of the brain that are believed to be associated with some symptoms. Lower values were associated with greater severity for symptoms like memory dysfunction, and anosmia. “Why there might be hypometabolism in these regions I think needs to be assessed and used as a biomarker to associate hypometabolism with other kinds of processes in blood and spinal fluid,” said Dr. Spudich.

Along with colleagues at Yale, Dr. Spudich is conducting the MIND study, which is using PET and MRI imaging along with blood and CSF biomarkers to track the progress of patients after COVID-19. There are few results to discuss since only 20 patients have been recruited so far, except that brain imaging and blood values are generally normal despite neurologic complaints. Most were not hospitalized for COVID-19. Dr. Spudich highlighted one man in his 30s who developed new-onset psychosis, despite no previous history. Although clinical tests were all negative, a novel autoantibody detection method revealed a previously unknown autoreactive antibody in his spinal fluid. “This may suggest that there is autoantibody production in some individuals with post–COVID-19 psychosis, and potentially other syndromes,” said Dr. Spudich.
 

The research task ahead

The case illustrates the task ahead for neurology. “There’s a real research mandate to understand the biological substrates of these diverse disorders, not only to address the emergent public health concern and reduce the stigma in our patients, but to develop targeted therapeutic interventions,” said Dr. Spudich.

Anna Cervantes-Arslanian, MD, an associate professor of neurology at Boston University who also treats and studies patients with post-COVID neurologic symptoms, agreed with that assessment. “It’s not like every patient that has muscle aches and fatigue also has brain fog. It’s really hard to parse them out into specific phenotypes that are pretty classic. Some people will have all of those things, some will have very few of them,” said Dr. Cervantes-Arslanian. “We need to be able to identify them sand see if there is clustering of symptoms so we can better look into what the biological underpinnings are. That’s the first step to thinking about a therapeutic target.”

Dr. Spudich and Dr. Cervantes-Arslanian had no relevant financial disclosures.

Long-haul neurologic symptoms of COVID-19 seem to be distinct from neurologic conditions found in acute disease. Among the patient population of long-haulers complaining of brain fog, muscular ache, and other issues, many had mild COVID-19. Much work remains to be done to understand the biological mechanisms behind these problems, but inflammation and autoimmune responses may play a role in some cases.

Those were some of the takeaways from a talk by Serena Spudich, MD, who presented her research at the 2021 annual meeting of the American Academy of Neurology. Dr. Spudich is the division chief of neurologic infections and global neurology and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
 

Examining the nervous system’s involvement in COVID-19

Even early on in the pandemic, it became clear that there were lingering complaints of neuromuscular problems, cognitive dysfunction, and mood and psychiatric issues. Breathing and heart rate problems also can arise. “There seems to be a preponderance of syndromes that reflect involvement of the nervous system,” said Dr. Spudich.

To try to understand the etiology of these persistent problems, Dr. Spudich said it’s important to examine the nervous system’s involvement in acute COVID-19. She has been involved in these efforts since early in the pandemic, when she ran an inpatient consult service at Yale dedicated to neurologic effects of acute COVID-19. She witnessed complications including stroke, encephalopathy, and seizures, among others.

Stroke during acute COVID-19 seemed to be associated with inflammation and endothelial activation or endotheliopathy. SARS-CoV-2 has been undetectable in the cerebrospinal fluid (CSF) of patients with acute COVID-19 and neurologic symptoms, but inflammatory cytokines can be present along with increased frequency of B cells. Anti–SARS-CoV-2 antibodies have also been found in CSF, some of which were auto reactive to brain tissue. The immune response was altered, compared with healthy controls, and in the CNS, compared with in the blood, “raising the question of whether inflammation and autoimmunity may be underlying causes of these syndromes,” said Dr. Spudich.

She also pointed to an MRI study of autopsied brain tissue of patients with COVID-19 and neurologic complications, which showed indications of both hemorrhagic and ischemic microvascular injury. “It’s just a reminder that, during acute COVID-19, there may be inflammation in the brain, there may be autoimmune reactions, and there may be vascular changes that underlie some of the neurologic syndromes that are seen,” said Dr. Spudich.
 

A panoply of different syndromes

In October, Yale set up a post-COVID neurologic clinic that brought together pulmonary, cardiology, and psychiatric specialists, many of whom saw the same patients, about 60% of whom had cognitive impairment, more than 40% had neuromuscular problems, and over 30% headache. “There’s not a single entity of a post-COVID neurologic syndrome. There’s a panoply of different syndromes that may have similar or distinct etiologies,” said Dr. Spudich.

Most patients were in their 30s, 40s, or 50s. That doesn’t necessarily mean this is the most common age range for these issues, though. There could be some bias if these individuals are seeking specialty care because they expected to recover from COVID-19 quickly. But it could be that there is something biologically unique among this age group that predisposes them to complications. Regardless, two out of three patients were never hospitalized, “suggesting that even mild COVID-19 can lead to some long-term sequelae,” said Dr. Spudich.

One potential explanation for long-term neurologic syndromes is that they are an extension of the inflammation, autoimmunity, and immune perturbation occurring during acute disease. One study looked at 18 cancer patients who had neurologic complications with COVID-19. Two months after onset, they had elevated markers of neuroinflammation and neuronal injury in the cerebral spinal fluid compared to cancer patients with no history of COVID-19.
 

Looking for biologic markers

An Italian study looked at patients who were evaluated during acute hospitalization and again 3 months later, and found that some markers of inflation in the blood were associated with later cognitive impairment. The patients were more severely ill, so it’s not clear what the findings mean for patients who present with neurologic symptoms after milder illness.

A PET scan study of 35 patients with persistent neurologic symptoms found patterns of reduced fluorodeoxyglucose uptake in some regions of the brain that are believed to be associated with some symptoms. Lower values were associated with greater severity for symptoms like memory dysfunction, and anosmia. “Why there might be hypometabolism in these regions I think needs to be assessed and used as a biomarker to associate hypometabolism with other kinds of processes in blood and spinal fluid,” said Dr. Spudich.

Along with colleagues at Yale, Dr. Spudich is conducting the MIND study, which is using PET and MRI imaging along with blood and CSF biomarkers to track the progress of patients after COVID-19. There are few results to discuss since only 20 patients have been recruited so far, except that brain imaging and blood values are generally normal despite neurologic complaints. Most were not hospitalized for COVID-19. Dr. Spudich highlighted one man in his 30s who developed new-onset psychosis, despite no previous history. Although clinical tests were all negative, a novel autoantibody detection method revealed a previously unknown autoreactive antibody in his spinal fluid. “This may suggest that there is autoantibody production in some individuals with post–COVID-19 psychosis, and potentially other syndromes,” said Dr. Spudich.
 

The research task ahead

The case illustrates the task ahead for neurology. “There’s a real research mandate to understand the biological substrates of these diverse disorders, not only to address the emergent public health concern and reduce the stigma in our patients, but to develop targeted therapeutic interventions,” said Dr. Spudich.

Anna Cervantes-Arslanian, MD, an associate professor of neurology at Boston University who also treats and studies patients with post-COVID neurologic symptoms, agreed with that assessment. “It’s not like every patient that has muscle aches and fatigue also has brain fog. It’s really hard to parse them out into specific phenotypes that are pretty classic. Some people will have all of those things, some will have very few of them,” said Dr. Cervantes-Arslanian. “We need to be able to identify them sand see if there is clustering of symptoms so we can better look into what the biological underpinnings are. That’s the first step to thinking about a therapeutic target.”

Dr. Spudich and Dr. Cervantes-Arslanian had no relevant financial disclosures.

Long-haul neurologic symptoms of COVID-19 seem to be distinct from neurologic conditions found in acute disease. Among the patient population of long-haulers complaining of brain fog, muscular ache, and other issues, many had mild COVID-19. Much work remains to be done to understand the biological mechanisms behind these problems, but inflammation and autoimmune responses may play a role in some cases.

Those were some of the takeaways from a talk by Serena Spudich, MD, who presented her research at the 2021 annual meeting of the American Academy of Neurology. Dr. Spudich is the division chief of neurologic infections and global neurology and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.
 

Examining the nervous system’s involvement in COVID-19

Even early on in the pandemic, it became clear that there were lingering complaints of neuromuscular problems, cognitive dysfunction, and mood and psychiatric issues. Breathing and heart rate problems also can arise. “There seems to be a preponderance of syndromes that reflect involvement of the nervous system,” said Dr. Spudich.

To try to understand the etiology of these persistent problems, Dr. Spudich said it’s important to examine the nervous system’s involvement in acute COVID-19. She has been involved in these efforts since early in the pandemic, when she ran an inpatient consult service at Yale dedicated to neurologic effects of acute COVID-19. She witnessed complications including stroke, encephalopathy, and seizures, among others.

Stroke during acute COVID-19 seemed to be associated with inflammation and endothelial activation or endotheliopathy. SARS-CoV-2 has been undetectable in the cerebrospinal fluid (CSF) of patients with acute COVID-19 and neurologic symptoms, but inflammatory cytokines can be present along with increased frequency of B cells. Anti–SARS-CoV-2 antibodies have also been found in CSF, some of which were auto reactive to brain tissue. The immune response was altered, compared with healthy controls, and in the CNS, compared with in the blood, “raising the question of whether inflammation and autoimmunity may be underlying causes of these syndromes,” said Dr. Spudich.

She also pointed to an MRI study of autopsied brain tissue of patients with COVID-19 and neurologic complications, which showed indications of both hemorrhagic and ischemic microvascular injury. “It’s just a reminder that, during acute COVID-19, there may be inflammation in the brain, there may be autoimmune reactions, and there may be vascular changes that underlie some of the neurologic syndromes that are seen,” said Dr. Spudich.
 

A panoply of different syndromes

In October, Yale set up a post-COVID neurologic clinic that brought together pulmonary, cardiology, and psychiatric specialists, many of whom saw the same patients, about 60% of whom had cognitive impairment, more than 40% had neuromuscular problems, and over 30% headache. “There’s not a single entity of a post-COVID neurologic syndrome. There’s a panoply of different syndromes that may have similar or distinct etiologies,” said Dr. Spudich.

Most patients were in their 30s, 40s, or 50s. That doesn’t necessarily mean this is the most common age range for these issues, though. There could be some bias if these individuals are seeking specialty care because they expected to recover from COVID-19 quickly. But it could be that there is something biologically unique among this age group that predisposes them to complications. Regardless, two out of three patients were never hospitalized, “suggesting that even mild COVID-19 can lead to some long-term sequelae,” said Dr. Spudich.

One potential explanation for long-term neurologic syndromes is that they are an extension of the inflammation, autoimmunity, and immune perturbation occurring during acute disease. One study looked at 18 cancer patients who had neurologic complications with COVID-19. Two months after onset, they had elevated markers of neuroinflammation and neuronal injury in the cerebral spinal fluid compared to cancer patients with no history of COVID-19.
 

Looking for biologic markers

An Italian study looked at patients who were evaluated during acute hospitalization and again 3 months later, and found that some markers of inflation in the blood were associated with later cognitive impairment. The patients were more severely ill, so it’s not clear what the findings mean for patients who present with neurologic symptoms after milder illness.

A PET scan study of 35 patients with persistent neurologic symptoms found patterns of reduced fluorodeoxyglucose uptake in some regions of the brain that are believed to be associated with some symptoms. Lower values were associated with greater severity for symptoms like memory dysfunction, and anosmia. “Why there might be hypometabolism in these regions I think needs to be assessed and used as a biomarker to associate hypometabolism with other kinds of processes in blood and spinal fluid,” said Dr. Spudich.

Along with colleagues at Yale, Dr. Spudich is conducting the MIND study, which is using PET and MRI imaging along with blood and CSF biomarkers to track the progress of patients after COVID-19. There are few results to discuss since only 20 patients have been recruited so far, except that brain imaging and blood values are generally normal despite neurologic complaints. Most were not hospitalized for COVID-19. Dr. Spudich highlighted one man in his 30s who developed new-onset psychosis, despite no previous history. Although clinical tests were all negative, a novel autoantibody detection method revealed a previously unknown autoreactive antibody in his spinal fluid. “This may suggest that there is autoantibody production in some individuals with post–COVID-19 psychosis, and potentially other syndromes,” said Dr. Spudich.
 

The research task ahead

The case illustrates the task ahead for neurology. “There’s a real research mandate to understand the biological substrates of these diverse disorders, not only to address the emergent public health concern and reduce the stigma in our patients, but to develop targeted therapeutic interventions,” said Dr. Spudich.

Anna Cervantes-Arslanian, MD, an associate professor of neurology at Boston University who also treats and studies patients with post-COVID neurologic symptoms, agreed with that assessment. “It’s not like every patient that has muscle aches and fatigue also has brain fog. It’s really hard to parse them out into specific phenotypes that are pretty classic. Some people will have all of those things, some will have very few of them,” said Dr. Cervantes-Arslanian. “We need to be able to identify them sand see if there is clustering of symptoms so we can better look into what the biological underpinnings are. That’s the first step to thinking about a therapeutic target.”

Dr. Spudich and Dr. Cervantes-Arslanian had no relevant financial disclosures.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Two new large international studies have found relatively low rates of stroke in patients hospitalized with COVID-19. One study showed a stroke rate of 2.2% among patients with COVID-19 admitted to intensive care in 52 different countries. Another found a stroke rate of 1.48% in patients hospitalized with COVID-19 from 70 different countries. These researchers also found a reduction in stroke presentations and stroke care during the pandemic.

Both studies will be presented at the American Academy of Neurology’s 2021 annual meeting.

“Stroke has been a known serious complication of COVID-19, with some studies reporting a higher-than-expected occurrence, especially in young people,” said coauthor of the intensive care study, Jonathon Fanning, MBBS, PhD, University of Queensland, Brisbane, Australia.

“However, among the sickest of COVID patients – those admitted to an ICU – our research found that stroke was not a common complication and that ischemic stroke did not increase the risk of death,” he added.
 

Hemorrhagic stroke more common?

In this study, researchers analyzed a database of 2,699 patients who were admitted to the intensive care unit with COVID-19 in 52 countries and found that 59 of these patients (2.2%) subsequently sustained a stroke. 

Most of the strokes identified in this cohort were hemorrhagic (46%), with 32% being ischemic and 22% unspecified. Hemorrhagic stroke was associated with a fivefold increased risk for death compared with patients who did not have a stroke. Of those with a hemorrhagic stroke, 72% died, but only 15% died of the stroke. Rather, multiorgan failure was the leading cause of death.

There was no association between ischemic stroke and mortality.

“There is scarce research on new-onset stroke complicating ICU admissions, and many of the limitations of assessing stroke in ICU populations confound the true values and result in variability in reported incidence anywhere from a 1%-4% incidence,” Dr. Fanning said. 

He noted that a  large Korean study had shown a 1.2% rate of stroke in patients without COVID admitted to non-neurologic ICUs. “In light of this, I think this 2% is higher than we would expect in a general ICU population, but in the context of earlier reports of COVID-19–associated risk for stroke, this figure is actually somewhat reassuring,” Dr. Fanning said.  

Asked how this study compared with the large American Heart Association study recently reported that showed an overall rate of ischemic stroke of 0.75%, Dr. Fanning said the two studies reported on different populations, which makes them difficult to compare.

“Our study specifically reports on new-onset stroke complicating ICU admission,” he noted. “The AHA study is a large study of all patients admitted to hospital, but both studies identified less than previous estimates of COVID-related stroke.”
 

Largest sample to date  

The other study, which includes 119,967 COVID-19 hospitalizations and represents the largest sample reporting the concomitant diagnoses of stroke and SARS-CoV-2 infection to date, was presented at the AAN meeting by Thanh N. Nguyen, MD, a professor at Boston University.

This study has also been published online in Neurology, with first author Raul G. Nogueira, MD, Emory University, Atlanta.  

In this international observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers, there was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722) of all stroke admissions, which numbered 52,026.

The researchers identified stroke diagnoses by the International Classification of Diseases, 10th revision, codes and/or classifications in stroke center databases, and rates of stroke hospitalizations and numbers of patients receiving thrombolysis were compared between the first 4 months of the pandemic (March to June 2020) compared with two control 4-month periods.
 

Global decline in stroke care during pandemic

Results showed a global decline in the number of stroke patients admitted to the hospital as well as acute stroke treatments, such as thrombolysis, during the first wave of the COVID-19 pandemic. The researchers found that there were 91,373 stroke admissions in the 4 months immediately before the pandemic, compared with 80,894 admissions during the first 4 pandemic months, representing an 11.5% decline.

They also report that 13,334 stroke patients received intravenous thrombolysis in the 4 months preceding the pandemic, compared with 11,570 during the first 4 pandemic months, representing a 13.2% drop.

Interhospital transfers after thrombolysis for a higher level of stroke care decreased from 1,337 before the pandemic to 1,178 during the pandemic, a reduction of 11.9%.  

There were greater declines in primary compared with comprehensive stroke centers for stroke hospitalizations (change, –17.3% vs. –10.3%) and for the number of patients receiving thrombolysis (change, –15.5% vs. –12.6%).

The volume of stroke hospitalizations increased by 9.5% in the two later pandemic months (May, June) versus the two earlier months (March, April), with greater recovery in hospitals with lower COVID-19 hospitalization volume, high-volume stroke centers, and comprehensive stroke centers.

Dr. Nguyen suggested that reasons for the reductions in these stroke numbers at the beginning of the pandemic could include a reduction in stroke risk due to a reduction of exposure to other viral infections or patients not presenting to the hospital for fear of contracting the coronavirus.

The higher recovery of stroke volume in high-volume stroke centers and comprehensive stroke centers may represent patients with higher needs – those having more severe strokes – seeking care more frequently than those with milder symptoms, she noted.

“Preserving access to stroke care and emergency stroke care amidst a pandemic is as important as educating patients on the importance of presenting to the hospital in the event of stroke-like symptoms,” Dr. Nguyen concluded.

“We continue to advocate that if a patient has stroke-like symptoms, such as loss of speech, strength, vision, or balance, it is important for the patient to seek medical care as an emergency, as there are treatments that can improve a patient’s ability to recover from disabling stroke in earlier rather than later time windows,” she added.

In the publication, the authors wrote, “Our results concur with other recent reports on the collateral effects of the COVID-19 pandemic on stroke systems of care,” but added that “this is among the first descriptions of the change at a global level, including primary and comprehensive stroke centers.”

They said that hospital access related to high COVID-19 burden was unlikely a factor because the decline was seen in centers with a few or no patients with COVID-19. They suggested that patient fear of contracting coronavirus may have played a role, along with a decrease in presentation of transient ischemic attacks, mild strokes, or moderate strokes, and physical distancing measures may have prevented the timely witnessing of a stroke.

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

Two new large international studies have found relatively low rates of stroke in patients hospitalized with COVID-19. One study showed a stroke rate of 2.2% among patients with COVID-19 admitted to intensive care in 52 different countries. Another found a stroke rate of 1.48% in patients hospitalized with COVID-19 from 70 different countries. These researchers also found a reduction in stroke presentations and stroke care during the pandemic.

Both studies will be presented at the American Academy of Neurology’s 2021 annual meeting.

“Stroke has been a known serious complication of COVID-19, with some studies reporting a higher-than-expected occurrence, especially in young people,” said coauthor of the intensive care study, Jonathon Fanning, MBBS, PhD, University of Queensland, Brisbane, Australia.

“However, among the sickest of COVID patients – those admitted to an ICU – our research found that stroke was not a common complication and that ischemic stroke did not increase the risk of death,” he added.
 

Hemorrhagic stroke more common?

In this study, researchers analyzed a database of 2,699 patients who were admitted to the intensive care unit with COVID-19 in 52 countries and found that 59 of these patients (2.2%) subsequently sustained a stroke. 

Most of the strokes identified in this cohort were hemorrhagic (46%), with 32% being ischemic and 22% unspecified. Hemorrhagic stroke was associated with a fivefold increased risk for death compared with patients who did not have a stroke. Of those with a hemorrhagic stroke, 72% died, but only 15% died of the stroke. Rather, multiorgan failure was the leading cause of death.

There was no association between ischemic stroke and mortality.

“There is scarce research on new-onset stroke complicating ICU admissions, and many of the limitations of assessing stroke in ICU populations confound the true values and result in variability in reported incidence anywhere from a 1%-4% incidence,” Dr. Fanning said. 

He noted that a  large Korean study had shown a 1.2% rate of stroke in patients without COVID admitted to non-neurologic ICUs. “In light of this, I think this 2% is higher than we would expect in a general ICU population, but in the context of earlier reports of COVID-19–associated risk for stroke, this figure is actually somewhat reassuring,” Dr. Fanning said.  

Asked how this study compared with the large American Heart Association study recently reported that showed an overall rate of ischemic stroke of 0.75%, Dr. Fanning said the two studies reported on different populations, which makes them difficult to compare.

“Our study specifically reports on new-onset stroke complicating ICU admission,” he noted. “The AHA study is a large study of all patients admitted to hospital, but both studies identified less than previous estimates of COVID-related stroke.”
 

Largest sample to date  

The other study, which includes 119,967 COVID-19 hospitalizations and represents the largest sample reporting the concomitant diagnoses of stroke and SARS-CoV-2 infection to date, was presented at the AAN meeting by Thanh N. Nguyen, MD, a professor at Boston University.

This study has also been published online in Neurology, with first author Raul G. Nogueira, MD, Emory University, Atlanta.  

In this international observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers, there was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722) of all stroke admissions, which numbered 52,026.

The researchers identified stroke diagnoses by the International Classification of Diseases, 10th revision, codes and/or classifications in stroke center databases, and rates of stroke hospitalizations and numbers of patients receiving thrombolysis were compared between the first 4 months of the pandemic (March to June 2020) compared with two control 4-month periods.
 

Global decline in stroke care during pandemic

Results showed a global decline in the number of stroke patients admitted to the hospital as well as acute stroke treatments, such as thrombolysis, during the first wave of the COVID-19 pandemic. The researchers found that there were 91,373 stroke admissions in the 4 months immediately before the pandemic, compared with 80,894 admissions during the first 4 pandemic months, representing an 11.5% decline.

They also report that 13,334 stroke patients received intravenous thrombolysis in the 4 months preceding the pandemic, compared with 11,570 during the first 4 pandemic months, representing a 13.2% drop.

Interhospital transfers after thrombolysis for a higher level of stroke care decreased from 1,337 before the pandemic to 1,178 during the pandemic, a reduction of 11.9%.  

There were greater declines in primary compared with comprehensive stroke centers for stroke hospitalizations (change, –17.3% vs. –10.3%) and for the number of patients receiving thrombolysis (change, –15.5% vs. –12.6%).

The volume of stroke hospitalizations increased by 9.5% in the two later pandemic months (May, June) versus the two earlier months (March, April), with greater recovery in hospitals with lower COVID-19 hospitalization volume, high-volume stroke centers, and comprehensive stroke centers.

Dr. Nguyen suggested that reasons for the reductions in these stroke numbers at the beginning of the pandemic could include a reduction in stroke risk due to a reduction of exposure to other viral infections or patients not presenting to the hospital for fear of contracting the coronavirus.

The higher recovery of stroke volume in high-volume stroke centers and comprehensive stroke centers may represent patients with higher needs – those having more severe strokes – seeking care more frequently than those with milder symptoms, she noted.

“Preserving access to stroke care and emergency stroke care amidst a pandemic is as important as educating patients on the importance of presenting to the hospital in the event of stroke-like symptoms,” Dr. Nguyen concluded.

“We continue to advocate that if a patient has stroke-like symptoms, such as loss of speech, strength, vision, or balance, it is important for the patient to seek medical care as an emergency, as there are treatments that can improve a patient’s ability to recover from disabling stroke in earlier rather than later time windows,” she added.

In the publication, the authors wrote, “Our results concur with other recent reports on the collateral effects of the COVID-19 pandemic on stroke systems of care,” but added that “this is among the first descriptions of the change at a global level, including primary and comprehensive stroke centers.”

They said that hospital access related to high COVID-19 burden was unlikely a factor because the decline was seen in centers with a few or no patients with COVID-19. They suggested that patient fear of contracting coronavirus may have played a role, along with a decrease in presentation of transient ischemic attacks, mild strokes, or moderate strokes, and physical distancing measures may have prevented the timely witnessing of a stroke.

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

Two new large international studies have found relatively low rates of stroke in patients hospitalized with COVID-19. One study showed a stroke rate of 2.2% among patients with COVID-19 admitted to intensive care in 52 different countries. Another found a stroke rate of 1.48% in patients hospitalized with COVID-19 from 70 different countries. These researchers also found a reduction in stroke presentations and stroke care during the pandemic.

Both studies will be presented at the American Academy of Neurology’s 2021 annual meeting.

“Stroke has been a known serious complication of COVID-19, with some studies reporting a higher-than-expected occurrence, especially in young people,” said coauthor of the intensive care study, Jonathon Fanning, MBBS, PhD, University of Queensland, Brisbane, Australia.

“However, among the sickest of COVID patients – those admitted to an ICU – our research found that stroke was not a common complication and that ischemic stroke did not increase the risk of death,” he added.
 

Hemorrhagic stroke more common?

In this study, researchers analyzed a database of 2,699 patients who were admitted to the intensive care unit with COVID-19 in 52 countries and found that 59 of these patients (2.2%) subsequently sustained a stroke. 

Most of the strokes identified in this cohort were hemorrhagic (46%), with 32% being ischemic and 22% unspecified. Hemorrhagic stroke was associated with a fivefold increased risk for death compared with patients who did not have a stroke. Of those with a hemorrhagic stroke, 72% died, but only 15% died of the stroke. Rather, multiorgan failure was the leading cause of death.

There was no association between ischemic stroke and mortality.

“There is scarce research on new-onset stroke complicating ICU admissions, and many of the limitations of assessing stroke in ICU populations confound the true values and result in variability in reported incidence anywhere from a 1%-4% incidence,” Dr. Fanning said. 

He noted that a  large Korean study had shown a 1.2% rate of stroke in patients without COVID admitted to non-neurologic ICUs. “In light of this, I think this 2% is higher than we would expect in a general ICU population, but in the context of earlier reports of COVID-19–associated risk for stroke, this figure is actually somewhat reassuring,” Dr. Fanning said.  

Asked how this study compared with the large American Heart Association study recently reported that showed an overall rate of ischemic stroke of 0.75%, Dr. Fanning said the two studies reported on different populations, which makes them difficult to compare.

“Our study specifically reports on new-onset stroke complicating ICU admission,” he noted. “The AHA study is a large study of all patients admitted to hospital, but both studies identified less than previous estimates of COVID-related stroke.”
 

Largest sample to date  

The other study, which includes 119,967 COVID-19 hospitalizations and represents the largest sample reporting the concomitant diagnoses of stroke and SARS-CoV-2 infection to date, was presented at the AAN meeting by Thanh N. Nguyen, MD, a professor at Boston University.

This study has also been published online in Neurology, with first author Raul G. Nogueira, MD, Emory University, Atlanta.  

In this international observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers, there was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722) of all stroke admissions, which numbered 52,026.

The researchers identified stroke diagnoses by the International Classification of Diseases, 10th revision, codes and/or classifications in stroke center databases, and rates of stroke hospitalizations and numbers of patients receiving thrombolysis were compared between the first 4 months of the pandemic (March to June 2020) compared with two control 4-month periods.
 

Global decline in stroke care during pandemic

Results showed a global decline in the number of stroke patients admitted to the hospital as well as acute stroke treatments, such as thrombolysis, during the first wave of the COVID-19 pandemic. The researchers found that there were 91,373 stroke admissions in the 4 months immediately before the pandemic, compared with 80,894 admissions during the first 4 pandemic months, representing an 11.5% decline.

They also report that 13,334 stroke patients received intravenous thrombolysis in the 4 months preceding the pandemic, compared with 11,570 during the first 4 pandemic months, representing a 13.2% drop.

Interhospital transfers after thrombolysis for a higher level of stroke care decreased from 1,337 before the pandemic to 1,178 during the pandemic, a reduction of 11.9%.  

There were greater declines in primary compared with comprehensive stroke centers for stroke hospitalizations (change, –17.3% vs. –10.3%) and for the number of patients receiving thrombolysis (change, –15.5% vs. –12.6%).

The volume of stroke hospitalizations increased by 9.5% in the two later pandemic months (May, June) versus the two earlier months (March, April), with greater recovery in hospitals with lower COVID-19 hospitalization volume, high-volume stroke centers, and comprehensive stroke centers.

Dr. Nguyen suggested that reasons for the reductions in these stroke numbers at the beginning of the pandemic could include a reduction in stroke risk due to a reduction of exposure to other viral infections or patients not presenting to the hospital for fear of contracting the coronavirus.

The higher recovery of stroke volume in high-volume stroke centers and comprehensive stroke centers may represent patients with higher needs – those having more severe strokes – seeking care more frequently than those with milder symptoms, she noted.

“Preserving access to stroke care and emergency stroke care amidst a pandemic is as important as educating patients on the importance of presenting to the hospital in the event of stroke-like symptoms,” Dr. Nguyen concluded.

“We continue to advocate that if a patient has stroke-like symptoms, such as loss of speech, strength, vision, or balance, it is important for the patient to seek medical care as an emergency, as there are treatments that can improve a patient’s ability to recover from disabling stroke in earlier rather than later time windows,” she added.

In the publication, the authors wrote, “Our results concur with other recent reports on the collateral effects of the COVID-19 pandemic on stroke systems of care,” but added that “this is among the first descriptions of the change at a global level, including primary and comprehensive stroke centers.”

They said that hospital access related to high COVID-19 burden was unlikely a factor because the decline was seen in centers with a few or no patients with COVID-19. They suggested that patient fear of contracting coronavirus may have played a role, along with a decrease in presentation of transient ischemic attacks, mild strokes, or moderate strokes, and physical distancing measures may have prevented the timely witnessing of a stroke.

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

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.

Not that it’s without controversy.

The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.

“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).

“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.

“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.

“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.

Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
 

Top 10 reasons

They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:

• The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
• Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
• Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
• Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
• Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
• Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
• Investigators found SARS-CoV-2 in hospital air filters and building ducts.
• It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
• No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
• Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.

“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.

“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.

The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
 

Response to a review

The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”

However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”

The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”

Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.

“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”

As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”

The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.

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

For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reported in children were up for the fourth time in 5 weeks, rising from 73,000 to over 88,000 for the week of April 9-15. That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.

Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.

Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.

Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.

There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.

[email protected]

For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reported in children were up for the fourth time in 5 weeks, rising from 73,000 to over 88,000 for the week of April 9-15. That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.

Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.

Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.

Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.

There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.

[email protected]

For the first time since the pandemic began, children’s share of weekly COVID-19 cases topped 20% in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reported in children were up for the fourth time in 5 weeks, rising from 73,000 to over 88,000 for the week of April 9-15. That represented 20.6% of all new cases for the week, eclipsing the previous high of 19.1% recorded just 3 weeks ago, based on data collected by the AAP and CHA from 49 states, the District of Columbia, New York City, Puerto Rico, and Guam.

Cumulative cases of COVID-19 in children exceed 3.6 million in those jurisdictions, which is 13.6% of the total reported among all ages, and the overall rate of coronavirus infection is 4,824 cases per 100,000 children in the population, the AAP and CHA said in their weekly COVID-19 report.

Among the 53 reporting jurisdictions, North Dakota has the highest cumulative rate, 9,167 per 100,000 children, followed by Tennessee (8,580), South Carolina (7,948), South Dakota (7,938), and Connecticut (7,707). Children’s share of cumulative cases is highest in Vermont, at 21.9%, with Alaska next at 20.0% and Wyoming at 19.2%, the AAP and CHA said.

Since the beginning of April, the largest local increases in cases reported came in Michigan (21.6%), Vermont (15.9%), and Maine (15.6%). Nationally, the increase over those same 2 weeks is just under 5%, the two organizations noted.

There were 5 deaths among children during the week of April 9-15, bringing the total to 297, but the recent increases in cases have not affected the long-term trends for serious illness. The death rate for children with COVID-19 has been 0.01% since early November – 43 states, New York City, Puerto Rico, and Guam are reporting such data – and the hospitalization rate has been 0.8% since mid-January in 24 states and New York City, the AAP/CHA data show.

[email protected]