COVID-19 Updates

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

rfranki@mdedge.com

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

rfranki@mdedge.com

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

rfranki@mdedge.com

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

If everything goes as planned, the Pfizer and Moderna mRNA COVID-19 vaccines could be granted emergency use authorization (EUA) for children aged 12 years and older by the fall of 2021.

Courtesy Dr. Maldonado

According to Yvonne Maldonado, MD, Pfizer has fully enrolled adolescent trials and Moderna is currently enrolling 3,000 adolescents in a safety and reactogenicity trial known as TeenCOVE, in which participants will receive an intramuscular injection of 100 mcg mRNA-1273 on day 1 and on day 29. Meanwhile, Johnson & Johnson and AstraZeneca will be starting to enroll older children and adolescents into studies within the next several weeks.

The companies are also planning to enroll younger children, Dr. Maldonado, the Taube professor of global health and infectious diseases at Stanford (Calif.) University, said during the Society for Pediatric Dermatology pre-AAD meeting. “At least two of the vaccine companies have indicated that they would like to start enrolling children as young as 2-5 years of age and eventually getting down to infants and toddlers if the vaccines prove to be safe and effective in the older children. Eventually, we hope to get to the level where we can have several vaccine candidates for all children 6 months of age and older.”

In the future, she said, infectious disease experts hope to see antiviral, immunomodulatory, anti-inflammatory, and monoclonal therapies for all populations including children, although trials in this population have not begun. “Clinical trials must be flexible and adaptive to deal with children and adolescents,” added Dr. Maldonado, who is also senior associate dean for faculty development and diversity at Stanford.

“We would ideally like to have new correlates of protection, as well as biomarkers to follow for evidence of effectiveness. We also would love to see vaccines in the pediatric population as soon as possible, because herd immunity is the ultimate goal for protection against this disease and prevention of additional transmission over time.” However, she said, the degree and durability of immunity has yet to be determined, and vaccine-associated immune effects are unknown. In the meantime, infectious disease researchers expect nonpharmacologic interventions, such as wearing face masks and social distancing to continue for an undefined period.

(Less than 2 weeks after Dr. Maldonado spoke at the SPD meeting, Pfizer announced in a press release that, in phase 3 clinical trials, the company’s coronavirus vaccine was 100% effective in protecting children aged 12-15 years from infection, with a “robust” antibody responses and side effects similar to those experienced by those aged 16-25 years. The company also announced that it plans to seek Food and Drug Administration EUA for this age group. Asked to comment on this update, Dr. Maldonado said the results released by Pfizer “suggest that their COVID-19 vaccine is very safe and highly effective in preventing COVID-19 among children 12-15 years of age.” She added that additional data from the Pfizer trials as well as from Moderna and Johnson & Johnson vaccine trials “will hopefully lead to FDA EUA review in the coming weeks,” and that COVID-19 vaccinations for children “may be possible by this summer.”)
 

_{Children with underlying diseases or on immune suppressants}

At the SPD meeting, an attendee asked if there were any pediatric patients for whom she would not recommend receiving a COVID-19 vaccine because of an underlying disease or concurrent therapy with immune suppressants. “We don’t have those data yet,” Dr. Maldonado said. “Based on what we’re seeing with adults, it does appear that those with underlying conditions are at somewhat higher risk of developing severe infection and may therefore most likely to need vaccination. Most of those risks are cardiovascular, obesity, and other factors, but not necessarily immunocompromising conditions. More likely what we’re seeing is that people with underlying immunocompromising conditions may not mount a good response to the vaccines at this time. It doesn’t mean we shouldn’t give the vaccines, but we need to learn more about that.”

Dr. Maldonado went on to note that, as vaccine manufacturers commence pediatric trials, healthy children will be tested first, followed in due time with children who have immunocompromised conditions. “The question will be whether or not we should give monoclonal antibodies to those particular children to help boost their immunity to SARS-CoV-2, because they might not have a good response to the vaccines,” she said. “Those things need to be sorted out, but there’s no safety signal or concerns at this point for vaccine to be given to immunocompromised individuals.”

Another meeting attendee asked Dr. Maldonado if she thinks there is a practical role for assessing markers of T-cell immunity when evaluating suspected COVID-19 patients who may test negative on serology, Dr. Maldonado said that she and her colleagues are seeking pediatric patients who were treated for COVID-19 at Stanford, in an effort to sort this out.

They are checking peripheral blood mononuclear cells in these patients “to try and tease out what the immune response is in kids who have serious disease, versus those who came in with acute disease, versus those who are asymptomatic,” and comparing them with children who don’t have infection, she explained. “The question is, what is the role of T cells and how much do they contribute? One of the biggest questions we have is, do we have an immune correlate? Can we detect a particular level of neutralizing antibody that seems to be protective? If so, how long is it protective, and can we look for T- and B-cell memory cells and effector vector cells and see how long those effector vector cells can be active in protection? Those are studies that are ongoing now.”

Dr. Maldonado disclosed that she is a member of the data safety monitoring board for a non–COVID-19 vaccine being developed by Pfizer.

dbrunk@mdedge.com

If everything goes as planned, the Pfizer and Moderna mRNA COVID-19 vaccines could be granted emergency use authorization (EUA) for children aged 12 years and older by the fall of 2021.

Courtesy Dr. Maldonado

According to Yvonne Maldonado, MD, Pfizer has fully enrolled adolescent trials and Moderna is currently enrolling 3,000 adolescents in a safety and reactogenicity trial known as TeenCOVE, in which participants will receive an intramuscular injection of 100 mcg mRNA-1273 on day 1 and on day 29. Meanwhile, Johnson & Johnson and AstraZeneca will be starting to enroll older children and adolescents into studies within the next several weeks.

The companies are also planning to enroll younger children, Dr. Maldonado, the Taube professor of global health and infectious diseases at Stanford (Calif.) University, said during the Society for Pediatric Dermatology pre-AAD meeting. “At least two of the vaccine companies have indicated that they would like to start enrolling children as young as 2-5 years of age and eventually getting down to infants and toddlers if the vaccines prove to be safe and effective in the older children. Eventually, we hope to get to the level where we can have several vaccine candidates for all children 6 months of age and older.”

In the future, she said, infectious disease experts hope to see antiviral, immunomodulatory, anti-inflammatory, and monoclonal therapies for all populations including children, although trials in this population have not begun. “Clinical trials must be flexible and adaptive to deal with children and adolescents,” added Dr. Maldonado, who is also senior associate dean for faculty development and diversity at Stanford.

“We would ideally like to have new correlates of protection, as well as biomarkers to follow for evidence of effectiveness. We also would love to see vaccines in the pediatric population as soon as possible, because herd immunity is the ultimate goal for protection against this disease and prevention of additional transmission over time.” However, she said, the degree and durability of immunity has yet to be determined, and vaccine-associated immune effects are unknown. In the meantime, infectious disease researchers expect nonpharmacologic interventions, such as wearing face masks and social distancing to continue for an undefined period.

(Less than 2 weeks after Dr. Maldonado spoke at the SPD meeting, Pfizer announced in a press release that, in phase 3 clinical trials, the company’s coronavirus vaccine was 100% effective in protecting children aged 12-15 years from infection, with a “robust” antibody responses and side effects similar to those experienced by those aged 16-25 years. The company also announced that it plans to seek Food and Drug Administration EUA for this age group. Asked to comment on this update, Dr. Maldonado said the results released by Pfizer “suggest that their COVID-19 vaccine is very safe and highly effective in preventing COVID-19 among children 12-15 years of age.” She added that additional data from the Pfizer trials as well as from Moderna and Johnson & Johnson vaccine trials “will hopefully lead to FDA EUA review in the coming weeks,” and that COVID-19 vaccinations for children “may be possible by this summer.”)
 

_{Children with underlying diseases or on immune suppressants}

At the SPD meeting, an attendee asked if there were any pediatric patients for whom she would not recommend receiving a COVID-19 vaccine because of an underlying disease or concurrent therapy with immune suppressants. “We don’t have those data yet,” Dr. Maldonado said. “Based on what we’re seeing with adults, it does appear that those with underlying conditions are at somewhat higher risk of developing severe infection and may therefore most likely to need vaccination. Most of those risks are cardiovascular, obesity, and other factors, but not necessarily immunocompromising conditions. More likely what we’re seeing is that people with underlying immunocompromising conditions may not mount a good response to the vaccines at this time. It doesn’t mean we shouldn’t give the vaccines, but we need to learn more about that.”

Dr. Maldonado went on to note that, as vaccine manufacturers commence pediatric trials, healthy children will be tested first, followed in due time with children who have immunocompromised conditions. “The question will be whether or not we should give monoclonal antibodies to those particular children to help boost their immunity to SARS-CoV-2, because they might not have a good response to the vaccines,” she said. “Those things need to be sorted out, but there’s no safety signal or concerns at this point for vaccine to be given to immunocompromised individuals.”

Another meeting attendee asked Dr. Maldonado if she thinks there is a practical role for assessing markers of T-cell immunity when evaluating suspected COVID-19 patients who may test negative on serology, Dr. Maldonado said that she and her colleagues are seeking pediatric patients who were treated for COVID-19 at Stanford, in an effort to sort this out.

They are checking peripheral blood mononuclear cells in these patients “to try and tease out what the immune response is in kids who have serious disease, versus those who came in with acute disease, versus those who are asymptomatic,” and comparing them with children who don’t have infection, she explained. “The question is, what is the role of T cells and how much do they contribute? One of the biggest questions we have is, do we have an immune correlate? Can we detect a particular level of neutralizing antibody that seems to be protective? If so, how long is it protective, and can we look for T- and B-cell memory cells and effector vector cells and see how long those effector vector cells can be active in protection? Those are studies that are ongoing now.”

Dr. Maldonado disclosed that she is a member of the data safety monitoring board for a non–COVID-19 vaccine being developed by Pfizer.

dbrunk@mdedge.com

If everything goes as planned, the Pfizer and Moderna mRNA COVID-19 vaccines could be granted emergency use authorization (EUA) for children aged 12 years and older by the fall of 2021.

Courtesy Dr. Maldonado

According to Yvonne Maldonado, MD, Pfizer has fully enrolled adolescent trials and Moderna is currently enrolling 3,000 adolescents in a safety and reactogenicity trial known as TeenCOVE, in which participants will receive an intramuscular injection of 100 mcg mRNA-1273 on day 1 and on day 29. Meanwhile, Johnson & Johnson and AstraZeneca will be starting to enroll older children and adolescents into studies within the next several weeks.

The companies are also planning to enroll younger children, Dr. Maldonado, the Taube professor of global health and infectious diseases at Stanford (Calif.) University, said during the Society for Pediatric Dermatology pre-AAD meeting. “At least two of the vaccine companies have indicated that they would like to start enrolling children as young as 2-5 years of age and eventually getting down to infants and toddlers if the vaccines prove to be safe and effective in the older children. Eventually, we hope to get to the level where we can have several vaccine candidates for all children 6 months of age and older.”

In the future, she said, infectious disease experts hope to see antiviral, immunomodulatory, anti-inflammatory, and monoclonal therapies for all populations including children, although trials in this population have not begun. “Clinical trials must be flexible and adaptive to deal with children and adolescents,” added Dr. Maldonado, who is also senior associate dean for faculty development and diversity at Stanford.

“We would ideally like to have new correlates of protection, as well as biomarkers to follow for evidence of effectiveness. We also would love to see vaccines in the pediatric population as soon as possible, because herd immunity is the ultimate goal for protection against this disease and prevention of additional transmission over time.” However, she said, the degree and durability of immunity has yet to be determined, and vaccine-associated immune effects are unknown. In the meantime, infectious disease researchers expect nonpharmacologic interventions, such as wearing face masks and social distancing to continue for an undefined period.

(Less than 2 weeks after Dr. Maldonado spoke at the SPD meeting, Pfizer announced in a press release that, in phase 3 clinical trials, the company’s coronavirus vaccine was 100% effective in protecting children aged 12-15 years from infection, with a “robust” antibody responses and side effects similar to those experienced by those aged 16-25 years. The company also announced that it plans to seek Food and Drug Administration EUA for this age group. Asked to comment on this update, Dr. Maldonado said the results released by Pfizer “suggest that their COVID-19 vaccine is very safe and highly effective in preventing COVID-19 among children 12-15 years of age.” She added that additional data from the Pfizer trials as well as from Moderna and Johnson & Johnson vaccine trials “will hopefully lead to FDA EUA review in the coming weeks,” and that COVID-19 vaccinations for children “may be possible by this summer.”)
 

_{Children with underlying diseases or on immune suppressants}

At the SPD meeting, an attendee asked if there were any pediatric patients for whom she would not recommend receiving a COVID-19 vaccine because of an underlying disease or concurrent therapy with immune suppressants. “We don’t have those data yet,” Dr. Maldonado said. “Based on what we’re seeing with adults, it does appear that those with underlying conditions are at somewhat higher risk of developing severe infection and may therefore most likely to need vaccination. Most of those risks are cardiovascular, obesity, and other factors, but not necessarily immunocompromising conditions. More likely what we’re seeing is that people with underlying immunocompromising conditions may not mount a good response to the vaccines at this time. It doesn’t mean we shouldn’t give the vaccines, but we need to learn more about that.”

Dr. Maldonado went on to note that, as vaccine manufacturers commence pediatric trials, healthy children will be tested first, followed in due time with children who have immunocompromised conditions. “The question will be whether or not we should give monoclonal antibodies to those particular children to help boost their immunity to SARS-CoV-2, because they might not have a good response to the vaccines,” she said. “Those things need to be sorted out, but there’s no safety signal or concerns at this point for vaccine to be given to immunocompromised individuals.”

Another meeting attendee asked Dr. Maldonado if she thinks there is a practical role for assessing markers of T-cell immunity when evaluating suspected COVID-19 patients who may test negative on serology, Dr. Maldonado said that she and her colleagues are seeking pediatric patients who were treated for COVID-19 at Stanford, in an effort to sort this out.

They are checking peripheral blood mononuclear cells in these patients “to try and tease out what the immune response is in kids who have serious disease, versus those who came in with acute disease, versus those who are asymptomatic,” and comparing them with children who don’t have infection, she explained. “The question is, what is the role of T cells and how much do they contribute? One of the biggest questions we have is, do we have an immune correlate? Can we detect a particular level of neutralizing antibody that seems to be protective? If so, how long is it protective, and can we look for T- and B-cell memory cells and effector vector cells and see how long those effector vector cells can be active in protection? Those are studies that are ongoing now.”

Dr. Maldonado disclosed that she is a member of the data safety monitoring board for a non–COVID-19 vaccine being developed by Pfizer.

dbrunk@mdedge.com

Phase III clinical trials show that Pfizer’s coronavirus vaccine is 100% effective in protecting children aged 12-15 years from infection, the company said in a news release.

The study enrolled 2,260 adolescents aged 12-15. No infections were reported in the group given the vaccine produced by Pfizer and its European partner, BioNTech, the release said. The placebo group reported 18 cases of COVID-19.

The vaccinated children showed a strong antibody response with no serious side effects.

Albert Bourla, PhD, chairman and CEO of Pfizer, said the company plans to seek Food and Drug Administration emergency use authorization, which could allow this age group to be vaccinated before the start of the next school year. Pfizer will also seek authorization from the European Medicines Agency.

“We share the urgency to expand the authorization of our vaccine to use in younger populations and are encouraged by the clinical trial data from adolescents between the ages of 12 and 15,” Dr. Bourla said in the release.

The clinical trials showed a stronger response in children aged 12-15 than the 95% effectiveness reported in clinical trials in adults. The Pfizer vaccine is now authorized to be given to people aged 16 and up in the United States.

Health experts said the clinical trials – while not peer-reviewed – amounted to very good news.

“The sooner that we can get vaccines into as many people as possible, regardless of their age, the sooner we will be able to really feel like we’re ending this pandemic for good,” Angela Rasmussen, PhD, a virologist affiliated with Georgetown University in Washington, told The New York Times.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, recently said that getting children vaccinated is an important step toward achieving herd immunity.

“We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape,” he said earlier in March during a hearing of the Senate Health, Education, Labor, and Pensions Committee. “We ultimately would like to get and have to get children into that mix.”

Pfizer said it started clinical trials during the week of March 23 with children aged 5-11 and will next start trials with children aged 2-5, followed by children aged 6 months to 2 years. Vaccine makers Moderna and AstraZeneca also have started clinical trials in younger children.

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

Phase III clinical trials show that Pfizer’s coronavirus vaccine is 100% effective in protecting children aged 12-15 years from infection, the company said in a news release.

The study enrolled 2,260 adolescents aged 12-15. No infections were reported in the group given the vaccine produced by Pfizer and its European partner, BioNTech, the release said. The placebo group reported 18 cases of COVID-19.

The vaccinated children showed a strong antibody response with no serious side effects.

Albert Bourla, PhD, chairman and CEO of Pfizer, said the company plans to seek Food and Drug Administration emergency use authorization, which could allow this age group to be vaccinated before the start of the next school year. Pfizer will also seek authorization from the European Medicines Agency.

“We share the urgency to expand the authorization of our vaccine to use in younger populations and are encouraged by the clinical trial data from adolescents between the ages of 12 and 15,” Dr. Bourla said in the release.

The clinical trials showed a stronger response in children aged 12-15 than the 95% effectiveness reported in clinical trials in adults. The Pfizer vaccine is now authorized to be given to people aged 16 and up in the United States.

Health experts said the clinical trials – while not peer-reviewed – amounted to very good news.

“The sooner that we can get vaccines into as many people as possible, regardless of their age, the sooner we will be able to really feel like we’re ending this pandemic for good,” Angela Rasmussen, PhD, a virologist affiliated with Georgetown University in Washington, told The New York Times.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, recently said that getting children vaccinated is an important step toward achieving herd immunity.

“We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape,” he said earlier in March during a hearing of the Senate Health, Education, Labor, and Pensions Committee. “We ultimately would like to get and have to get children into that mix.”

Pfizer said it started clinical trials during the week of March 23 with children aged 5-11 and will next start trials with children aged 2-5, followed by children aged 6 months to 2 years. Vaccine makers Moderna and AstraZeneca also have started clinical trials in younger children.

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

Phase III clinical trials show that Pfizer’s coronavirus vaccine is 100% effective in protecting children aged 12-15 years from infection, the company said in a news release.

The study enrolled 2,260 adolescents aged 12-15. No infections were reported in the group given the vaccine produced by Pfizer and its European partner, BioNTech, the release said. The placebo group reported 18 cases of COVID-19.

The vaccinated children showed a strong antibody response with no serious side effects.

Albert Bourla, PhD, chairman and CEO of Pfizer, said the company plans to seek Food and Drug Administration emergency use authorization, which could allow this age group to be vaccinated before the start of the next school year. Pfizer will also seek authorization from the European Medicines Agency.

“We share the urgency to expand the authorization of our vaccine to use in younger populations and are encouraged by the clinical trial data from adolescents between the ages of 12 and 15,” Dr. Bourla said in the release.

The clinical trials showed a stronger response in children aged 12-15 than the 95% effectiveness reported in clinical trials in adults. The Pfizer vaccine is now authorized to be given to people aged 16 and up in the United States.

Health experts said the clinical trials – while not peer-reviewed – amounted to very good news.

“The sooner that we can get vaccines into as many people as possible, regardless of their age, the sooner we will be able to really feel like we’re ending this pandemic for good,” Angela Rasmussen, PhD, a virologist affiliated with Georgetown University in Washington, told The New York Times.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, recently said that getting children vaccinated is an important step toward achieving herd immunity.

“We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape,” he said earlier in March during a hearing of the Senate Health, Education, Labor, and Pensions Committee. “We ultimately would like to get and have to get children into that mix.”

Pfizer said it started clinical trials during the week of March 23 with children aged 5-11 and will next start trials with children aged 2-5, followed by children aged 6 months to 2 years. Vaccine makers Moderna and AstraZeneca also have started clinical trials in younger children.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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