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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.

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

President Joe Biden has tested positive for COVID-19, the White House announced today.

Biden, 79, is experiencing “very mild” symptoms, White House Press Secretary Karine Jean-Pierre said in a statement. The president is fully vaccinated and has been boosted twice and has started taking the antiviral Paxlovid since testing positive, Ms. Jean-Pierre said.

President Biden plans to isolate at the White House and “will continue to carry out all of his duties fully during that time,” the statement said.

“He has been in contact with members of the White House staff by phone this morning, and will participate in his planned meetings at the White House this morning via phone and Zoom from the residence.”

President Biden will return to in-person work after he tests negative.

This is a developing story. Please check back for updates. A version of this article first appeared on WebMD.com .

Pregnant women who get infected with SARS-CoV-2 in their third trimester are almost three times as likely to have a preterm birth, while infection after 34 weeks’ gestation raises this risk sevenfold, based on the largest matched population-based cohort study published to date.

These findings support previous studies, underscoring the need for pregnant women and their families to take preventive measures against infection, lead author Noga Fallach, MA, of the Kahn-Sagol-Maccabi Research and Innovation Center, Tel Aviv, and colleagues reported.

ArtMarie/E+/Getty Images

Past research has suggested that COVID-19 may cause low birth weights and preterm birth in pregnant women, but those studies didn’t report outcomes for each trimester, the investigators wrote in PLoS ONE, noting that “timing of viral infection during fetal development may affect birth and other health outcomes.”

To address this knowledge gap, the investigators looked back at data from 2,703 pregnant women in Israel who tested positive for SARS-CoV-2 from Feb. 21, 2020, to July 2, 2021. Pregnancy outcomes in these women were compared with outcomes in an equal number of uninfected pregnant women. Vaccination status was not reported.

Comparing the two groups showed that catching COVID-19 in the third trimester was linked with nearly triple the risk of preterm birth (odds ratio, 2.76; 95% confidence interval, 1.63-4.67), and more than quadruple the risk if COVID-19 symptoms were present (OR, 4.28; 95% CI, 1.94-9.41). Women who tested positive for SARS-CoV-2 after 34 weeks’ gestation were seven times more likely than uninfected women to deliver early (OR, 7.10; 95% CI, 2.44-20.61).

Pregnant women who caught COVID-19 in the first two trimesters were not significantly more likely to have a preterm birth. Infection was not associated with abnormally low birth rates, or pregnancy loss, in any trimester.

Tal Patalon, MD, coauthor and head of the Kahn-Sagol-Maccabi Research and Innovation Center, focused on these more optimistic findings in an interview.

“The results are encouraging, and reassuring that COVID-19 infection during pregnancy is not associated with any type of pregnancy loss,” Dr. Patalon said.

She also pointed out that the women in the study were infected with SARS-CoV-2 variants that are no longer common.

“It should be remembered that the research group tested the COVID-19 pre-Delta variants, and does not refer to the dominant variant today, which is Omicron,” Dr. Patalon said.

Still, the investigators concluded that the “results underline the importance of preventive measures taken against SARS-CoV-2 infection among pregnant women and their families.”

Sonja A. Rasmussen, MD, of the University of Florida, Gainesville, said that the issue with out-of-date variants in published research has been one of the “real challenges” in studying the ever-evolving COVID-19 pandemic; however, it’s not a good enough reason to dismiss this study.

“I think at this point, we need to assume that it applies to Omicron too,” Dr. Rasmussen said, noting that other respiratory viruses, like influenza, have also been shown to increase the risk of preterm birth when contracted in late pregnancy.

While the present findings highlight the risk of infection in the third trimester, Dr. Rasmussen advised women in all stages of pregnancy to protect themselves against COVID-19, based on the knowledge that illness in a mother can affect normal growth and development in a fetus, even if it doesn’t lead to preterm birth.

“A mom getting sick during pregnancy is not good for the baby,” Dr. Rasmussen said. “The baby’s really dependent on the mom. So you want that baby to have good nutrition throughout the pregnancy. It’s just as important earlier on as later. And you want that baby to get good oxygenation no matter what time [in the pregnancy]. I know that people want a little bit of a break [from preventive measures]. But I would emphasize that if you’re pregnant, we do all sorts of things during pregnancy to make sure that our babies are safe and healthy, and I would continue that for the whole pregnancy.”

Specifically, Dr. Rasmussen advised social distancing, use of an N95 mask, and vaccination. Getting vaccinated during pregnancy helps newborns fight off infection until 6 months of age, she added, when they become eligible for vaccination themselves. This added benefit was recently reported in a study published in the New England Journal of Medicine , for which Dr. Rasmussen cowrote an editorial .

“Vaccines have been approved for 6 months and older,” Dr. Rasmussen said. “But what do you do in those first 6 months of life? That’s a high-risk time for kids.”

Despite these risks, convincing pregnant women to get vaccinated remains a key challenge for health care providers, according to Dr. Rasmussen, even with an abundance of safety data. “Early on [in the pandemic], we said we didn’t know a lot about risks. We knew that other vaccines were safe during pregnancy, but we didn’t have a lot of information about a COVID-19 vaccine. But now we have a lot of data on safety during pregnancy, and these vaccines appear to be completely safe, based on the information we have. There have been many, many pregnant women vaccinated in the United States and in other countries.”

For reluctant expecting mothers, Dr. Rasmussen offered some words of advice: “I know that you worry about anything you do when you’re pregnant. But this is something that you can do to help your baby – now, to make a preterm birth less likely, and later, after the baby is born.

“The most important thing is for the pregnant person to hear this [vaccine recommendation] from their doctor,” she added. “If they’re going to listen to anybody, they’re going to listen to their physician. That’s what the data have shown for a long time.”

The investigators and Dr. Rasmussen disclosed no conflicts of interest.

Pregnant women who get infected with SARS-CoV-2 in their third trimester are almost three times as likely to have a preterm birth, while infection after 34 weeks’ gestation raises this risk sevenfold, based on the largest matched population-based cohort study published to date.

These findings support previous studies, underscoring the need for pregnant women and their families to take preventive measures against infection, lead author Noga Fallach, MA, of the Kahn-Sagol-Maccabi Research and Innovation Center, Tel Aviv, and colleagues reported.

ArtMarie/E+/Getty Images

Past research has suggested that COVID-19 may cause low birth weights and preterm birth in pregnant women, but those studies didn’t report outcomes for each trimester, the investigators wrote in PLoS ONE, noting that “timing of viral infection during fetal development may affect birth and other health outcomes.”

To address this knowledge gap, the investigators looked back at data from 2,703 pregnant women in Israel who tested positive for SARS-CoV-2 from Feb. 21, 2020, to July 2, 2021. Pregnancy outcomes in these women were compared with outcomes in an equal number of uninfected pregnant women. Vaccination status was not reported.

Comparing the two groups showed that catching COVID-19 in the third trimester was linked with nearly triple the risk of preterm birth (odds ratio, 2.76; 95% confidence interval, 1.63-4.67), and more than quadruple the risk if COVID-19 symptoms were present (OR, 4.28; 95% CI, 1.94-9.41). Women who tested positive for SARS-CoV-2 after 34 weeks’ gestation were seven times more likely than uninfected women to deliver early (OR, 7.10; 95% CI, 2.44-20.61).

Pregnant women who caught COVID-19 in the first two trimesters were not significantly more likely to have a preterm birth. Infection was not associated with abnormally low birth rates, or pregnancy loss, in any trimester.

Tal Patalon, MD, coauthor and head of the Kahn-Sagol-Maccabi Research and Innovation Center, focused on these more optimistic findings in an interview.

“The results are encouraging, and reassuring that COVID-19 infection during pregnancy is not associated with any type of pregnancy loss,” Dr. Patalon said.

She also pointed out that the women in the study were infected with SARS-CoV-2 variants that are no longer common.

“It should be remembered that the research group tested the COVID-19 pre-Delta variants, and does not refer to the dominant variant today, which is Omicron,” Dr. Patalon said.

Still, the investigators concluded that the “results underline the importance of preventive measures taken against SARS-CoV-2 infection among pregnant women and their families.”

Sonja A. Rasmussen, MD, of the University of Florida, Gainesville, said that the issue with out-of-date variants in published research has been one of the “real challenges” in studying the ever-evolving COVID-19 pandemic; however, it’s not a good enough reason to dismiss this study.

“I think at this point, we need to assume that it applies to Omicron too,” Dr. Rasmussen said, noting that other respiratory viruses, like influenza, have also been shown to increase the risk of preterm birth when contracted in late pregnancy.

While the present findings highlight the risk of infection in the third trimester, Dr. Rasmussen advised women in all stages of pregnancy to protect themselves against COVID-19, based on the knowledge that illness in a mother can affect normal growth and development in a fetus, even if it doesn’t lead to preterm birth.

“A mom getting sick during pregnancy is not good for the baby,” Dr. Rasmussen said. “The baby’s really dependent on the mom. So you want that baby to have good nutrition throughout the pregnancy. It’s just as important earlier on as later. And you want that baby to get good oxygenation no matter what time [in the pregnancy]. I know that people want a little bit of a break [from preventive measures]. But I would emphasize that if you’re pregnant, we do all sorts of things during pregnancy to make sure that our babies are safe and healthy, and I would continue that for the whole pregnancy.”

Specifically, Dr. Rasmussen advised social distancing, use of an N95 mask, and vaccination. Getting vaccinated during pregnancy helps newborns fight off infection until 6 months of age, she added, when they become eligible for vaccination themselves. This added benefit was recently reported in a study published in the New England Journal of Medicine , for which Dr. Rasmussen cowrote an editorial .

“Vaccines have been approved for 6 months and older,” Dr. Rasmussen said. “But what do you do in those first 6 months of life? That’s a high-risk time for kids.”

Despite these risks, convincing pregnant women to get vaccinated remains a key challenge for health care providers, according to Dr. Rasmussen, even with an abundance of safety data. “Early on [in the pandemic], we said we didn’t know a lot about risks. We knew that other vaccines were safe during pregnancy, but we didn’t have a lot of information about a COVID-19 vaccine. But now we have a lot of data on safety during pregnancy, and these vaccines appear to be completely safe, based on the information we have. There have been many, many pregnant women vaccinated in the United States and in other countries.”

For reluctant expecting mothers, Dr. Rasmussen offered some words of advice: “I know that you worry about anything you do when you’re pregnant. But this is something that you can do to help your baby – now, to make a preterm birth less likely, and later, after the baby is born.

“The most important thing is for the pregnant person to hear this [vaccine recommendation] from their doctor,” she added. “If they’re going to listen to anybody, they’re going to listen to their physician. That’s what the data have shown for a long time.”

The investigators and Dr. Rasmussen disclosed no conflicts of interest.

Pregnant women who get infected with SARS-CoV-2 in their third trimester are almost three times as likely to have a preterm birth, while infection after 34 weeks’ gestation raises this risk sevenfold, based on the largest matched population-based cohort study published to date.

These findings support previous studies, underscoring the need for pregnant women and their families to take preventive measures against infection, lead author Noga Fallach, MA, of the Kahn-Sagol-Maccabi Research and Innovation Center, Tel Aviv, and colleagues reported.

ArtMarie/E+/Getty Images

Past research has suggested that COVID-19 may cause low birth weights and preterm birth in pregnant women, but those studies didn’t report outcomes for each trimester, the investigators wrote in PLoS ONE, noting that “timing of viral infection during fetal development may affect birth and other health outcomes.”

To address this knowledge gap, the investigators looked back at data from 2,703 pregnant women in Israel who tested positive for SARS-CoV-2 from Feb. 21, 2020, to July 2, 2021. Pregnancy outcomes in these women were compared with outcomes in an equal number of uninfected pregnant women. Vaccination status was not reported.

Comparing the two groups showed that catching COVID-19 in the third trimester was linked with nearly triple the risk of preterm birth (odds ratio, 2.76; 95% confidence interval, 1.63-4.67), and more than quadruple the risk if COVID-19 symptoms were present (OR, 4.28; 95% CI, 1.94-9.41). Women who tested positive for SARS-CoV-2 after 34 weeks’ gestation were seven times more likely than uninfected women to deliver early (OR, 7.10; 95% CI, 2.44-20.61).

Pregnant women who caught COVID-19 in the first two trimesters were not significantly more likely to have a preterm birth. Infection was not associated with abnormally low birth rates, or pregnancy loss, in any trimester.

Tal Patalon, MD, coauthor and head of the Kahn-Sagol-Maccabi Research and Innovation Center, focused on these more optimistic findings in an interview.

“The results are encouraging, and reassuring that COVID-19 infection during pregnancy is not associated with any type of pregnancy loss,” Dr. Patalon said.

She also pointed out that the women in the study were infected with SARS-CoV-2 variants that are no longer common.

“It should be remembered that the research group tested the COVID-19 pre-Delta variants, and does not refer to the dominant variant today, which is Omicron,” Dr. Patalon said.

Still, the investigators concluded that the “results underline the importance of preventive measures taken against SARS-CoV-2 infection among pregnant women and their families.”

Sonja A. Rasmussen, MD, of the University of Florida, Gainesville, said that the issue with out-of-date variants in published research has been one of the “real challenges” in studying the ever-evolving COVID-19 pandemic; however, it’s not a good enough reason to dismiss this study.

“I think at this point, we need to assume that it applies to Omicron too,” Dr. Rasmussen said, noting that other respiratory viruses, like influenza, have also been shown to increase the risk of preterm birth when contracted in late pregnancy.

While the present findings highlight the risk of infection in the third trimester, Dr. Rasmussen advised women in all stages of pregnancy to protect themselves against COVID-19, based on the knowledge that illness in a mother can affect normal growth and development in a fetus, even if it doesn’t lead to preterm birth.

“A mom getting sick during pregnancy is not good for the baby,” Dr. Rasmussen said. “The baby’s really dependent on the mom. So you want that baby to have good nutrition throughout the pregnancy. It’s just as important earlier on as later. And you want that baby to get good oxygenation no matter what time [in the pregnancy]. I know that people want a little bit of a break [from preventive measures]. But I would emphasize that if you’re pregnant, we do all sorts of things during pregnancy to make sure that our babies are safe and healthy, and I would continue that for the whole pregnancy.”

Specifically, Dr. Rasmussen advised social distancing, use of an N95 mask, and vaccination. Getting vaccinated during pregnancy helps newborns fight off infection until 6 months of age, she added, when they become eligible for vaccination themselves. This added benefit was recently reported in a study published in the New England Journal of Medicine , for which Dr. Rasmussen cowrote an editorial .

“Vaccines have been approved for 6 months and older,” Dr. Rasmussen said. “But what do you do in those first 6 months of life? That’s a high-risk time for kids.”

Despite these risks, convincing pregnant women to get vaccinated remains a key challenge for health care providers, according to Dr. Rasmussen, even with an abundance of safety data. “Early on [in the pandemic], we said we didn’t know a lot about risks. We knew that other vaccines were safe during pregnancy, but we didn’t have a lot of information about a COVID-19 vaccine. But now we have a lot of data on safety during pregnancy, and these vaccines appear to be completely safe, based on the information we have. There have been many, many pregnant women vaccinated in the United States and in other countries.”

For reluctant expecting mothers, Dr. Rasmussen offered some words of advice: “I know that you worry about anything you do when you’re pregnant. But this is something that you can do to help your baby – now, to make a preterm birth less likely, and later, after the baby is born.

“The most important thing is for the pregnant person to hear this [vaccine recommendation] from their doctor,” she added. “If they’re going to listen to anybody, they’re going to listen to their physician. That’s what the data have shown for a long time.”

The investigators and Dr. Rasmussen disclosed no conflicts of interest.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.

Pre-endoscopy viral testing may not be necessary to prevent coronavirus transmission from patients to endoscopy staff members, according to a new study published in Gut.

Instead, using personal protective equipment (PPE) and ensuring up-to-date COVID-19 vaccination among the medical team was found to be enough to substantially reduce the risk of spreading SARS-CoV-2, wrote Alexander Hann, Dr.med., gastroenterologist at University Hospital Würzburg in Germany, and colleagues.

“We suggest that pre-selection of patients using respective questionnaires, vaccination, and particularly PPE appears to be sufficient for the prevention of SARS-CoV-2 transmission in GI endoscopy,” they wrote.

Dr. Hann and colleagues analyzed 15,750 endoscopies performed by 29 staff members during the period between May 2020 and December 2021. The researchers looked at three test approaches: No testing (4,543 patients), rapid antigen testing (682 patients), and real-time PCR testing (10,465 patients). In addition, 60 endoscopies were performed in patients with known COVID-19. Overall, no staff members became infected with SARS-CoV-2 during the study period. In all three scenarios, staff used PPE, and the vaccination rate of the team was 97%.

University Hospital Würzburg, with a tertiary endoscopy unit, is located in an area that had medium COVID-19 incidence during the study period. The hospital, which is spatially divided into a center for operative medicine and a center for internal medicine, required a negative PCR test for all endoscopies in the operative medicine center. In the internal medicine center, a PCR test was required only for in-patient procedures. Starting in January 2021 a negative rapid antigen test was required for patients scheduled for complex procedures with overnight surveillance; outpatient endoscopy procedures did not require a test.

All patients were interviewed before admission for COVID-19 symptoms, close contact with infected people, and recent travel to high-risk countries. Moreover, some endoscopies were performed even if a patient had positive markers for COVID-19.

The clinical team wore recommended PPE, including a high-filter FFP2 mask, one pair of gloves, protective eyewear, and disposable gowns. For patients with known COVID-19, staff wore two pairs of gloves, a disposable hairnet, and a water-resistant disposable gown. In addition, endoscopies were performed in negative pressure intervention rooms.

Among the 29 staff members involved, 16 physicians and 13 assistants worked in the endoscopy unit for at least 2 days per week for at least 6 months. The hospital’s internal policy required medical staff to undergo PCR testing if a rapid antigen test was positive or symptoms developed. Staff were vaccinated with two doses of the Pfizer-BioNTech vaccine in January and February 2021. A single booster dose of the Pfizer or Moderna vaccine was administered in November and December 2021.

The clinical team was not tested routinely, so asymptomatic infections may have existed. Moreover, the relatively low COVID-19 incidence in the local area might have influenced the risk of transmission. “However, even at the end of 2021, when the incidence was increasing, we did not see any higher risk of transmission,” the researchers explained.

“An important limitation of our study relates to the new variant Omicron that was dominant in our local area after the analyzed time frame.” Additional studies may be needed to understand the risk of transmission with the latest Omicron variants, and given the additional costs and implications on routine activity, current testing guidelines may need to be reconsidered.

“Although our data were not part of a randomized prospective study, we were able to demonstrate on a fairly high number of patients that PPE measures in addition to a short interview for assessment of a patient’s individual risks appear to be highly effective to control transmission of SARS-CoV-2 during an endoscopy. ... Pre-procedural RT-PCR testing or RA testing did not show any additional benefit,” Dr. Hann and colleagues concluded.

The authors reported no conflicts of interest.

New COVID-19 cases rose for the second time in 3 weeks, as the effort to vaccinate the youngest children continued to slow after just 3 full weeks.

Nationally, over 75,000 children under age 5 years received their first dose of COVID-19 vaccine during the week of July 7-13. That number is down from the previous week – 118,000 from June 30 to July 6 – which, in turn, was lower than the 206,000 doses administered through the first 10 days after approval, based on data from the Centers for Disease Control and Prevention. That all adds up to just under 400,000 vaccinated children, or 2% of the eligible population under age 5, as of July 13.

State-level data, meanwhile, show considerable variation, the American Academy of Pediatrics noted in its weekly analysis of the CDC vaccine data. Vermont has already vaccinated 10.0% of children under age 5 years, and Massachusetts is at 9.5%, while Mississippi (0.3%), Alabama (0.5%), and Louisiana (0.8%) are still below 1%, the AAP said.
 

New cases show signs of steadying

The national count was up by 11.1% for the week of July 8-14, rising to 75,000 new cases, compared with 68,000 the previous week, but the recent trend seems to be leaning toward steadiness. The overall number has been between 67,000 and 76,000 over the past 4 weeks, alternating between rising and falling in that time span, according to data gathered by the AAP and the Children’s Hospital Association from state and territorial health departments.

Despite the absence of a significant surge this summer, though, the weekly numbers “are far higher than one year ago, July 15, 2021, when 24,000 child cases were reported,” the two groups said, also noting that several states have stopped updating their online dashboards over the past year, making the current total artificially low in comparison.

Taken with that grain of salt, the cumulative number of child cases since the start of the pandemic is just over 13.9 million, which represents 18.6% of all cases in the United States. That proportion has been declining in recent weeks and was as high as 19.0% as late as mid-May. “While COVID-19 cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases,” the AAP and CHA said.

New COVID-19 cases rose for the second time in 3 weeks, as the effort to vaccinate the youngest children continued to slow after just 3 full weeks.

Nationally, over 75,000 children under age 5 years received their first dose of COVID-19 vaccine during the week of July 7-13. That number is down from the previous week – 118,000 from June 30 to July 6 – which, in turn, was lower than the 206,000 doses administered through the first 10 days after approval, based on data from the Centers for Disease Control and Prevention. That all adds up to just under 400,000 vaccinated children, or 2% of the eligible population under age 5, as of July 13.

State-level data, meanwhile, show considerable variation, the American Academy of Pediatrics noted in its weekly analysis of the CDC vaccine data. Vermont has already vaccinated 10.0% of children under age 5 years, and Massachusetts is at 9.5%, while Mississippi (0.3%), Alabama (0.5%), and Louisiana (0.8%) are still below 1%, the AAP said.
 

New cases show signs of steadying

The national count was up by 11.1% for the week of July 8-14, rising to 75,000 new cases, compared with 68,000 the previous week, but the recent trend seems to be leaning toward steadiness. The overall number has been between 67,000 and 76,000 over the past 4 weeks, alternating between rising and falling in that time span, according to data gathered by the AAP and the Children’s Hospital Association from state and territorial health departments.

Despite the absence of a significant surge this summer, though, the weekly numbers “are far higher than one year ago, July 15, 2021, when 24,000 child cases were reported,” the two groups said, also noting that several states have stopped updating their online dashboards over the past year, making the current total artificially low in comparison.

Taken with that grain of salt, the cumulative number of child cases since the start of the pandemic is just over 13.9 million, which represents 18.6% of all cases in the United States. That proportion has been declining in recent weeks and was as high as 19.0% as late as mid-May. “While COVID-19 cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases,” the AAP and CHA said.

New COVID-19 cases rose for the second time in 3 weeks, as the effort to vaccinate the youngest children continued to slow after just 3 full weeks.

Nationally, over 75,000 children under age 5 years received their first dose of COVID-19 vaccine during the week of July 7-13. That number is down from the previous week – 118,000 from June 30 to July 6 – which, in turn, was lower than the 206,000 doses administered through the first 10 days after approval, based on data from the Centers for Disease Control and Prevention. That all adds up to just under 400,000 vaccinated children, or 2% of the eligible population under age 5, as of July 13.

State-level data, meanwhile, show considerable variation, the American Academy of Pediatrics noted in its weekly analysis of the CDC vaccine data. Vermont has already vaccinated 10.0% of children under age 5 years, and Massachusetts is at 9.5%, while Mississippi (0.3%), Alabama (0.5%), and Louisiana (0.8%) are still below 1%, the AAP said.
 

New cases show signs of steadying

The national count was up by 11.1% for the week of July 8-14, rising to 75,000 new cases, compared with 68,000 the previous week, but the recent trend seems to be leaning toward steadiness. The overall number has been between 67,000 and 76,000 over the past 4 weeks, alternating between rising and falling in that time span, according to data gathered by the AAP and the Children’s Hospital Association from state and territorial health departments.

Despite the absence of a significant surge this summer, though, the weekly numbers “are far higher than one year ago, July 15, 2021, when 24,000 child cases were reported,” the two groups said, also noting that several states have stopped updating their online dashboards over the past year, making the current total artificially low in comparison.

Taken with that grain of salt, the cumulative number of child cases since the start of the pandemic is just over 13.9 million, which represents 18.6% of all cases in the United States. That proportion has been declining in recent weeks and was as high as 19.0% as late as mid-May. “While COVID-19 cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases,” the AAP and CHA said.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Right ventricular (RV) dilation or dysfunction in patients hospitalized with acute COVID-19 is associated with an elevated risk for in-hospital death.
• The impact of RV dilation or dysfunction on in-hospital mortality is similar for patients with acute COVID-19 and those with influenza, pneumonia, or acute respiratory distress syndrome (ARDS), but COVID-19 patients have greater absolute in-hospital mortality.
• RV dilatation or dysfunction in patients with acute COVID-19 is associated with a diagnosis of venous thromboembolism and subsequent intubation and mechanical ventilation.

Why this matters

• Right ventricular dysfunction increases mortality risk in acute COVID-19, and this study shows that RV dilation and dysfunction among such hospitalized patients has a similar impact on risk for in-hospital death in acute COVID-19 and in other respiratory illnesses.
• The findings suggest that abnormal RV findings should be considered a mortality risk marker in patients with acute respiratory illness, especially COVID-19.

Study design

• The retrospective study involved 225 consecutive patients admitted for acute COVID-19 from March 2020 to February 2021 at four major hospitals in the same metropolitan region and a control group of 6,150 adults admitted to the hospital for influenza, pneumonia, or ARDS; mean age in the study cohort was 63 years.
• All participants underwent echocardiography during their hospitalization, including evaluation of any RV dilation or dysfunction.
• Associations between RV measurements and in-hospital mortality, the primary outcome, were adjusted for potential confounders.

Key results

• Patients in the COVID-19 group were more likely than were those in the control group to be male (66% vs. 54%; P < .001), to identify as Hispanic (38% vs. 15%; P < .001), and to have a higher mean body mass index (29.4 vs. 27.9 kg/m²; P = .008).
• Compared with the control group, patients in the COVID-19 group more often required admission to the intensive care unit (75% vs. 54%; P < .001), mechanical ventilation (P < .001), and initiation of renal replacement therapy (P = .002), and more often were diagnosed with deep-vein thrombosis or pulmonary embolism (25% vs. 14%; P < .001). The median length of hospital stay was 20 days in the COVID-19 group, compared with 10 days in the control group (P < .001).
• In-hospital mortality was 21.3% in the COVID-19 group and 11.8% in the control group (P = .001). Those hospitalized with COVID-19 had an adjusted relative risk (RR) of 1.54 (95% confidence interval [CI], 1.06-2.24; P = .02) for in-hospital mortality, compared with those hospitalized for other respiratory illnesses.
• Mild RV dilation was associated with an adjusted RR of 1.4 (95% CI, 1.17-1.69; P = .0003) for in-hospital death, and moderate to severe RV dilation was associated with an adjusted RR of 2.0 (95% CI, 1.62-2.47; P < .0001).
• The corresponding adjusted risks for mild RV dysfunction and greater-than-mild RV dysfunction were, respectively, 1.39 (95% CI, 1.10-1.77; P = .007) and 1.68 (95% CI, 1.17-2.42; P = .005).
• The RR for in-hospital mortality associated with RV dilation and dysfunction was similar in those with COVID-19 and those with other respiratory illness, but the former had a higher baseline risk that yielded a greater absolute risk in the COVID-19 group.

Limitations

• The study was based primarily on a retrospective review of electronic health records, which poses a risk for misclassification. 
• Echocardiography was performed without blinding operators to patient clinical status, and echocardiograms were interpreted in a single university hospital system, so were not externally validated.
• Because echocardiograms obtained during hospitalization could not be compared with previous echocardiograms, it could not be determined whether any of the patients had preexisting RV dilation or dysfunction.
• Strain imaging was not feasible in many cases.

Disclosures

• The study received no commercial funding.
• The authors disclosed no financial relationships.

This is a summary of a preprint research study, Association of Right Ventricular Dilation and Dysfunction on Echocardiogram With In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared With Other Acute Respiratory Illness, written by researchers at the University of California, San Francisco, department of medicine, and Zuckerberg San Francisco General Hospital, division of cardiology. A version of this article first appeared on Medscape.com.

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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