Covid ICYMI

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

Susan Snead used to live in an apartment complex for older adults. The complex had a nice dayroom, and neighbors would knock on her door every now and then to check in.

But despite not being lonely, Ms. Snead, 89, did live alone in downtown Charleston, S.C. Eventually, that became dangerous.

“I fell a few times,” she says. “I had to call somebody to come and get me up.”

Sometimes help would come from the apartment complex’s office. Sometimes it came with a police escort.

Over time, needing to make those calls became a burden. Making and keeping appointments with her doctor, something she had to do regularly, as she has diabetes, got harder, too.

“It kind of wore me out,” she says. “Like you’re going up a hill.”

As she was beginning to accept she could no longer live alone, Ms. Snead, an Air Force veteran, learned about a program run by the Department of Veterans Affairs called Medical Foster Home.

Medical foster homes are privately owned homes in which a licensed caregiver lives with and supervises residents around the clock. Caregivers help aging veterans with activities of daily living like bathing, cooking, making and getting to appointments, getting dressed, and taking daily medication.

Caregivers can take care of up to three residents in their home at a time. While most residents are veterans, caregivers sometimes care for non-veteran residents, such as a veteran’s spouse or a caregiver’s family member.

Veterans typically pay about $1,500 to $3,000 out-of-pocket per month for the service, depending on location.

According to the VA, the concept of medical foster homes has been around since 1999, when VA hospitals across the country began reaching out to people willing to provide live-in care for veterans. The option is led by local VA hospitals, which approve caregivers and provide administrative services. There are now 517 medical foster homes, the VA says.

Much like other residential care facilities, medical foster homes get regular inspections for safety, nutrition, and more.

In 2019, Ms. Snead signed up for the program. She expected to be cared for, but she found a sense of family with her caregiver, Wilhelmina Brown, and another veteran in the home.

Ms. Brown started taking care of people – but not necessarily veterans – in 1997 when her grandmother was unable to care for herself, she says.

“My grandmama carried me to church every Sunday, she carried me to the beach – everywhere she went, she took me with her,” Ms. Brown says. As her grandmother got older, “I said, ‘I’m going to take care of her in my home.’ ”

Caring for others must come from the heart, Ms. Brown says.

She cooks her residents’ meals three times a day with dietary restrictions in mind, washes their dishes, does their laundry, remembers birthdays, and plans little parties.

“That’s my family,” Ms. Brown says.

In 2020, the COVID-19 pandemic upended the world – but at the same time, it highlighted the advantages of the medical foster home model.

Home-based primary care keeps veterans out of nursing homes – something that became particularly important as COVID-19 hit nursing homes and long-term care facilities.

Caregivers in the system were also able to help veterans, often living in rural areas, pivot and adapt to telehealth during a time of crisis.

One study, published in the journal Geriatrics, set out to identify how medical foster homes were able to deliver safe, effective health care during the early stages of the pandemic.

Researchers interviewed 37 VA care providers at 16 rural medical foster home programs across the country. The interviews took place between December 2020 and February 2021. They found medical foster home caregivers, coordinators, and health care providers communicated to move office visits to the home, helped veterans navigate telehealth, advocated to get veterans vaccinated in-home, and relied on each other to fight social isolation.

Caregivers also adapted quickly to telehealth, according to Leah Haverhals, PhD, a health research scientist and communications director for the Seattle-Denver Center of Innovation for Veteran Centered and Value Driven Care, who led the study.

Most veterans in the foster home program are older and find new technology difficult to use.

Caregivers, coordinators, and health care providers were largely new to the technology, too.

While the study found that most veterans and caregivers preferred in-person care, they were able to work together to make the best of telehealth.

“That speaks to the nature of the care being given, being able to pivot in a crisis like that,” Dr. Haverhals says.

If caregivers didn’t already have computers or telehealth-compatible devices, the VA provided iPads that would connect to the internet using cellular signals. According to the study, this helped to overcome connectivity issues that may have caused problems in rural areas.

Ms. Snead says Ms. Brown helped a lot with her telehealth calls.

“If we had to do things over the phone or with video, she was able to set that up to work with the person on the other end. She knows a lot about that stuff – about computers and things like that,” Ms. Snead says, adding that she hadn’t worked with computers since retirement in 1998.

Telehealth helped health care providers identify infections and quickly prescribe antibiotics to veterans in rural areas and provide other care that was more safely delivered in private homes.

“The findings from our study highlighted that when working together for the common goal of keeping vulnerable populations like veterans in MFHs [medical foster homes] safe during times of crisis, adaptation and collaboration facilitated the ongoing provision of high-quality care,” Dr. Haverhals’s group wrote. “Such collaboration has been shown to be critical in recent research in the United States on supporting older adults during the pandemic.”

Cari Levy, MD, PhD, a professor at the University of Colorado at Denver, Aurora, and a co-author of the study, specializes in palliative and telenursing home care for the VA.

Dr. Levy, who has worked for the VA for about 20 years, says how medical foster homes provided care during the pandemic carries lessons for civilian clinics. One of the most important lessons, she says, is that medical professionals will need to provide more care where people are, especially in populations that are too sick to get to the clinic.

“For years, there was all this hope that telehealth would expand,” but it took a pandemic to authorize approval from federal agencies to explode, she says. “I shudder to think what would have happened if we didn’t have telehealth. Fortunately, it was the right time to be able to flip a switch.”

Crisis aside, Dr. Levy says her dream would be for health care providers to do more home-based care. The model allows people to preserve the relational aspects of medicine, which can counteract a lot of the moral injury and burnout in the field, she says, adding:

“I see this as the kind of medicine many people intended to do when they got into medicine.”

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

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

New COVID-19 cases rose for the second week in a row as cumulative cases among U.S. children passed the 14-million mark, but a recent survey shows that more than half of parents believe that the vaccine is a greater risk to children under age 5 years than the virus.

In a Kaiser Family Foundation survey conducted July 7-17, 53% of parents with children aged 6 months to 5 years said that the vaccine is “a bigger risk to their child’s health than getting infected with COVID-19, compared to 44% who say getting infected is the bigger risk,” KFF reported July 26.

More than 4 out of 10 of respondents (43%) said that they will “definitely not” get their eligible children vaccinated, while only 7% said that their children had already received it and 10% said their children would get it as soon as possible, according to the KFF survey, which had an overall sample size of 1,847 adults, including an oversample of 471 parents of children under age 5.

Vaccine initiation has been slow in the first month since it was approved for the youngest children. Just 2.8% of all eligible children under age 5 had received an initial dose as of July 19, compared with first-month uptake figures of more than 18% for the 5- to 11-year-olds and 27% for those aged 12-15, based on data from the Centers for Disease Control and Prevention.

The current rates for vaccination in those aged 5 and older look like this: 70.2% of 12- to 17-year-olds have received at least one dose, versus 37.1% of those aged 5-11. Just over 60% of the older children were fully vaccinated as of July 19, as were 30.2% of the 5- to 11-year-olds, the CDC reported on its COVID Data Tracker.
 

Number of new cases hits 2-month high

Despite the vaccine, SARS-CoV-2 and its various mutations have continued with their summer travels. With 92,000 newly infected children added for the week of July 15-21, there have now been a total of 14,003,497 pediatric cases reported since the start of the pandemic, which works out to 18.6% of cases in all ages, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report.

The 92,000 new cases represent an increase of almost 22% over the previous week and mark the highest 1-week count since May, when the total passed 100,000 for 2 consecutive weeks. More recently the trend had seemed more stable as weekly cases dropped twice and rose twice as the total hovered around 70,000, based on the data collected by the AAP and CHA from state and territorial health departments.

A different scenario has played out for emergency department visits and hospital admissions, which have risen steadily since the beginning of April. The admission rate for children aged 0-17, which was just 0.13 new patients per 100,000 population on April 11, was up to 0.44 per 100,000 on July 21. By comparison, the highest rate reached last year during the Delta surge was 0.47 per 100,000, based on CDC data.

The 7-day average of emergency dept. visits among the youngest age group, 0-11 years, shows the same general increase as hospital admissions, but the older children have diverged form that path (see graph). For those aged 12-15 and 16-17, hospitalizations started dropping in late May and into mid-June before climbing again, although more slowly than for the youngest group, the CDC data show.

The ED visit rate with diagnosed COVID among those aged 0-11, measured at 6.1% of all visits on July 19, is, in fact, considerably higher than at any time during the Delta surge last year, when it never passed 4.0%, although much lower than peak Omicron (14.1%). That 6.1% was also higher than any other age group on that day, adults included, the CDC said.

[email protected]

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

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

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

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

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

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

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.