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SARS-CoV-2 crosses placenta and infects brains of two infants: ‘This is a first’
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
, according to a study published online today in Pediatrics .
One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.
Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.
“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
Both infants negative for the virus at birth
The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.
Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.
Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.
Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.
“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.
Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.
Seizures started on day 1 of life
The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.
“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.
Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.
Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.
The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.
Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.
Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
Mothers had very different presentations
Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.
One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.
In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.
He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
Instances are rare
The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.
Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”
Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.
Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.
FROM PEDIATRICS
Doctor’s checklist for treating long COVID patients
Lisa McCorkell had a mild bout of COVID-19 in March 2020. Young and healthy, she assumed that she would bounce back quickly. But when her fatigue, shortness of breath, and brain fog persisted, she realized that she most likely had long COVID.
“Back then, we as patients basically coined the term,” she said. While her first primary care provider was sympathetic, they were unsure how to treat her. After her insurance changed, she ended up with a second primary care provider who didn’t take her symptoms seriously. “They dismissed my complaints and told me they were all in my head. I didn’t seek care for a while after that.”
Ms. McCorkell’s symptoms improved after her first COVID vaccine in the spring of 2021. She also finally found a new primary care doctor she could trust. But as one of the founders of the Patient-Led Research Collaborative, a group of researchers who study long COVID, she said many doctors still don’t know the hallmark symptoms of the condition or how to treat it.
“There’s still a lack of education on what long COVID is, and the symptoms associated with it,” she said. “Many of the symptoms that occur in long COVID are symptoms of other chronic conditions, such as chronic fatigue syndrome, that are often dismissed. And even if providers believe patients and send them for a workup, many of the routine blood and imaging tests come back normal.”
The term “long COVID” emerged in May 2020. And though the condition was recognized within a few months of the start of the pandemic, doctors weren’t sure how to screen or treat it.
While knowledge has developed since then, primary care doctors are still in a tough spot. They’re often the first providers that patients turn to when they have symptoms of long COVID.
“There’s no clear algorithm to pick up long COVID – there are no definite blood tests or biomarkers, or specific things to look for on a physical exam,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center, New York. “It’s a complicated disease that can impact every organ system of the body.”
Even so, emerging research has identified a checklist of sorts that doctors should consider when a patient seeks care for what appears to be long COVID. Among them: the key systems and organs impacted by the disease, the most common symptoms, useful therapeutic options for symptom management that have been found to help people with long COVID, and the best healthy lifestyle choices that doctors can recommend to help their patients
Here’s a closer look at each of these aspects, based on research and interviews with experts, patients, and doctors.
Key systems, organs impacted
About 10% of people who are infected with COVID-19 go on to have long COVID, according to a recent study that Ms. McCorkell helped coauthor. But more than 3 years into the pandemic, much about the condition is still a mystery.
COVID is a unique virus because it can spread far and wide in a patient’s body. A December 2022 study, published in Nature, autopsied 44 people who died of COVID and found that the virus could spread throughout the body and persist, in one case as long as 230 days after symptoms started.
“We know that there are dozens of symptoms across multiple organ systems,” said Ms. McCorkell. “That makes it harder for a primary care physician to connect the dots and associate it with COVID.”
A paper published in Nature Medicine proposed one way to help guide diagnosis. It divided symptoms into four groups:
- Cardiac and renal issues such as heart palpitations, chest pain, and kidney damage
- Sleep and anxiety problems like insomnia, waking up in the middle of the night, and anxiety
- In the musculoskeletal and nervous systems: musculoskeletal pain, osteoarthritis, and problems with mental skills
- In the digestive and respiratory systems: trouble breathing, asthma, stomach pain, nausea, and vomiting
There were also specific patterns in these groups. People in the first group were more likely to be older, male, have other conditions and to have been infected during the first wave of the COVID pandemic. People in the second group were over 60% female, and were more likely to have had previous allergies or asthma. The third group was also about 60% female, and many of them already had autoimmune conditions such as rheumatoid arthritis. Members of the fourth group – also 60% female – were the least likely of all the groups to have another condition.
This research is helpful, because it gives doctors a better sense of what conditions might make a patient more likely to get long COVID, as well as specific symptoms to look out for, said Steven Flanagan, MD, a physical medicine and rehabilitation specialist at New York University Langone Medical Center who also specializes in treating patients with long COVID.
But the “challenge there, though, for health care providers is that not everyone will fall neatly into one of these categories,” he stressed.
Checklist of symptoms
Although long COVID can be confusing, doctors say there are several symptoms that appear consistently that primary care providers should look out for, that could flag long COVID.
Postexertional malaise (PEM). This is different from simply feeling tired. “This term is often conflated with fatigue, but it’s very different,” said David Putrino, PhD, director of rehabilitation innovation at the Mount Sinai Health System in New York, who says that he sees it in about 90% of patients who come to his long COVID clinic.
PEM is the worsening of symptoms after physical or mental exertion. This usually occurs a day or 2 after the activity, but it can last for days, and sometimes weeks.
“It’s very different from fatigue, which is just a generalized tiredness, and exercise intolerance, where someone complains of not being able to do their usual workout on the treadmill,” he noted. “People with PEM are able to push through and do what they need to do, and then are hit with symptoms anywhere from 12 to 72 hours later.”
Dysautonomia. This is an umbrella term used to describe a dysfunction of the autonomic nervous system, which regulates bodily functions that you can’t control, like your blood pressure, heart rate, and breathing. This can cause symptoms such as heart palpitations, along with orthostatic intolerance, which means you can’t stand up for long without feeling faint or dizzy.
“In my practice, about 80% of patients meet criteria for dysautonomia,” said Dr. Putrino. Other research has found that it’s present in about two-thirds of long COVID patients.
One relatively easy way primary care providers can diagnose dysautonomia is to do the tilt table test. This helps check for postural orthostatic tachycardia syndrome (POTS), one of the most common forms of dysautonomia. During this exam, the patient lies flat on a table. As the head of the table is raised to an almost upright position, their heart rate and blood pressure are measured. Signs of POTS include an abnormal heart rate when you’re upright, as well as a worsening of symptoms.
Exercise intolerance. A review published in the journal JAMA Network Open analyzed 38 studies on long COVID and exercise and found that patients with the condition had a much harder time doing physical activity. Exercise capacity was reduced to levels that would be expected about a decade later in life, according to study authors.
“This is especially important because it can’t be explained just by deconditioning,” said Dr. Purpura. “Sometimes these patients are encouraged to ramp up exercise as a way to help with symptoms, but in these cases, encouraging them to push through can cause postexertional malaise, which sets patients back and delays recovery.”
While long COVID can cause dozens of symptoms, a paper Ms. McCorkell coauthored zeroed in on some of the most common ones: chest pain, heart palpitations, coughing, shortness of breath, belly pain, nausea, problems with mental skills, fatigue, disordered sleep, memory loss, ringing in the ears (tinnitus), erectile dysfunction, irregular menstruation, and worsened premenstrual syndrome.
While most primary care providers are familiar with some of these long COVID symptoms, they may not be aware of others.
“COVID itself seems to cause hormonal changes that can lead to erection and menstrual cycle problems,” explained Dr. Putrino. “But these may not be picked up in a visit if the patient is complaining of other signs of long COVID.”
It’s not just what symptoms are, but when they began to occur, he added. “Usually, these symptoms either start with the initial COVID infection, or begin sometime within 3 months after the acute COVID infection. That’s why it’s important for people with COVID to take notice of anything unusual that crops up within a month or 2 after getting sick.”
Can you prevent long COVID?
You can’t, but one of the best ways to reduce your risk is to get vaccinated. Getting at least one dose of a COVID vaccine before you test positive for COVID lowers your risk of long COVID by about 35% according to a study published in Antimicrobial Stewardship & Healthcare Epidemiology. Unvaccinated people who recovered from COVID, and then got a vaccine, lowered their own long COVID risk by 27%.
In addition, a study published in JAMA Internal Medicine found that women who were infected with COVID were less likely to go on to get long COVID and/or have less debilitating symptoms if they had a healthy lifestyle, which included the following: a healthy weight (a body mass index between 18.5 and 24.7 kg/m2), never-smoker, moderate alcohol consumption, a high-quality diet, 7-9 hours of sleep a night, and at least 150 minutes per week of physical activity
But Ms. McCorkell noted that she herself had a healthy preinfection lifestyle but got long COVID anyway, suggesting these approaches don’t work for everyone.
“I think one reason my symptoms weren’t addressed by primary care physicians for so long is because they looked at me and saw that I was young and healthy, so they dismissed my reports as being all in my head,” she explained. “But we know now anyone can get long COVID, regardless of age, health status, or disease severity. That’s why it’s so important that primary care physicians be able to recognize symptoms.”
A version of this article first appeared on WebMD.com.
Lisa McCorkell had a mild bout of COVID-19 in March 2020. Young and healthy, she assumed that she would bounce back quickly. But when her fatigue, shortness of breath, and brain fog persisted, she realized that she most likely had long COVID.
“Back then, we as patients basically coined the term,” she said. While her first primary care provider was sympathetic, they were unsure how to treat her. After her insurance changed, she ended up with a second primary care provider who didn’t take her symptoms seriously. “They dismissed my complaints and told me they were all in my head. I didn’t seek care for a while after that.”
Ms. McCorkell’s symptoms improved after her first COVID vaccine in the spring of 2021. She also finally found a new primary care doctor she could trust. But as one of the founders of the Patient-Led Research Collaborative, a group of researchers who study long COVID, she said many doctors still don’t know the hallmark symptoms of the condition or how to treat it.
“There’s still a lack of education on what long COVID is, and the symptoms associated with it,” she said. “Many of the symptoms that occur in long COVID are symptoms of other chronic conditions, such as chronic fatigue syndrome, that are often dismissed. And even if providers believe patients and send them for a workup, many of the routine blood and imaging tests come back normal.”
The term “long COVID” emerged in May 2020. And though the condition was recognized within a few months of the start of the pandemic, doctors weren’t sure how to screen or treat it.
While knowledge has developed since then, primary care doctors are still in a tough spot. They’re often the first providers that patients turn to when they have symptoms of long COVID.
“There’s no clear algorithm to pick up long COVID – there are no definite blood tests or biomarkers, or specific things to look for on a physical exam,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center, New York. “It’s a complicated disease that can impact every organ system of the body.”
Even so, emerging research has identified a checklist of sorts that doctors should consider when a patient seeks care for what appears to be long COVID. Among them: the key systems and organs impacted by the disease, the most common symptoms, useful therapeutic options for symptom management that have been found to help people with long COVID, and the best healthy lifestyle choices that doctors can recommend to help their patients
Here’s a closer look at each of these aspects, based on research and interviews with experts, patients, and doctors.
Key systems, organs impacted
About 10% of people who are infected with COVID-19 go on to have long COVID, according to a recent study that Ms. McCorkell helped coauthor. But more than 3 years into the pandemic, much about the condition is still a mystery.
COVID is a unique virus because it can spread far and wide in a patient’s body. A December 2022 study, published in Nature, autopsied 44 people who died of COVID and found that the virus could spread throughout the body and persist, in one case as long as 230 days after symptoms started.
“We know that there are dozens of symptoms across multiple organ systems,” said Ms. McCorkell. “That makes it harder for a primary care physician to connect the dots and associate it with COVID.”
A paper published in Nature Medicine proposed one way to help guide diagnosis. It divided symptoms into four groups:
- Cardiac and renal issues such as heart palpitations, chest pain, and kidney damage
- Sleep and anxiety problems like insomnia, waking up in the middle of the night, and anxiety
- In the musculoskeletal and nervous systems: musculoskeletal pain, osteoarthritis, and problems with mental skills
- In the digestive and respiratory systems: trouble breathing, asthma, stomach pain, nausea, and vomiting
There were also specific patterns in these groups. People in the first group were more likely to be older, male, have other conditions and to have been infected during the first wave of the COVID pandemic. People in the second group were over 60% female, and were more likely to have had previous allergies or asthma. The third group was also about 60% female, and many of them already had autoimmune conditions such as rheumatoid arthritis. Members of the fourth group – also 60% female – were the least likely of all the groups to have another condition.
This research is helpful, because it gives doctors a better sense of what conditions might make a patient more likely to get long COVID, as well as specific symptoms to look out for, said Steven Flanagan, MD, a physical medicine and rehabilitation specialist at New York University Langone Medical Center who also specializes in treating patients with long COVID.
But the “challenge there, though, for health care providers is that not everyone will fall neatly into one of these categories,” he stressed.
Checklist of symptoms
Although long COVID can be confusing, doctors say there are several symptoms that appear consistently that primary care providers should look out for, that could flag long COVID.
Postexertional malaise (PEM). This is different from simply feeling tired. “This term is often conflated with fatigue, but it’s very different,” said David Putrino, PhD, director of rehabilitation innovation at the Mount Sinai Health System in New York, who says that he sees it in about 90% of patients who come to his long COVID clinic.
PEM is the worsening of symptoms after physical or mental exertion. This usually occurs a day or 2 after the activity, but it can last for days, and sometimes weeks.
“It’s very different from fatigue, which is just a generalized tiredness, and exercise intolerance, where someone complains of not being able to do their usual workout on the treadmill,” he noted. “People with PEM are able to push through and do what they need to do, and then are hit with symptoms anywhere from 12 to 72 hours later.”
Dysautonomia. This is an umbrella term used to describe a dysfunction of the autonomic nervous system, which regulates bodily functions that you can’t control, like your blood pressure, heart rate, and breathing. This can cause symptoms such as heart palpitations, along with orthostatic intolerance, which means you can’t stand up for long without feeling faint or dizzy.
“In my practice, about 80% of patients meet criteria for dysautonomia,” said Dr. Putrino. Other research has found that it’s present in about two-thirds of long COVID patients.
One relatively easy way primary care providers can diagnose dysautonomia is to do the tilt table test. This helps check for postural orthostatic tachycardia syndrome (POTS), one of the most common forms of dysautonomia. During this exam, the patient lies flat on a table. As the head of the table is raised to an almost upright position, their heart rate and blood pressure are measured. Signs of POTS include an abnormal heart rate when you’re upright, as well as a worsening of symptoms.
Exercise intolerance. A review published in the journal JAMA Network Open analyzed 38 studies on long COVID and exercise and found that patients with the condition had a much harder time doing physical activity. Exercise capacity was reduced to levels that would be expected about a decade later in life, according to study authors.
“This is especially important because it can’t be explained just by deconditioning,” said Dr. Purpura. “Sometimes these patients are encouraged to ramp up exercise as a way to help with symptoms, but in these cases, encouraging them to push through can cause postexertional malaise, which sets patients back and delays recovery.”
While long COVID can cause dozens of symptoms, a paper Ms. McCorkell coauthored zeroed in on some of the most common ones: chest pain, heart palpitations, coughing, shortness of breath, belly pain, nausea, problems with mental skills, fatigue, disordered sleep, memory loss, ringing in the ears (tinnitus), erectile dysfunction, irregular menstruation, and worsened premenstrual syndrome.
While most primary care providers are familiar with some of these long COVID symptoms, they may not be aware of others.
“COVID itself seems to cause hormonal changes that can lead to erection and menstrual cycle problems,” explained Dr. Putrino. “But these may not be picked up in a visit if the patient is complaining of other signs of long COVID.”
It’s not just what symptoms are, but when they began to occur, he added. “Usually, these symptoms either start with the initial COVID infection, or begin sometime within 3 months after the acute COVID infection. That’s why it’s important for people with COVID to take notice of anything unusual that crops up within a month or 2 after getting sick.”
Can you prevent long COVID?
You can’t, but one of the best ways to reduce your risk is to get vaccinated. Getting at least one dose of a COVID vaccine before you test positive for COVID lowers your risk of long COVID by about 35% according to a study published in Antimicrobial Stewardship & Healthcare Epidemiology. Unvaccinated people who recovered from COVID, and then got a vaccine, lowered their own long COVID risk by 27%.
In addition, a study published in JAMA Internal Medicine found that women who were infected with COVID were less likely to go on to get long COVID and/or have less debilitating symptoms if they had a healthy lifestyle, which included the following: a healthy weight (a body mass index between 18.5 and 24.7 kg/m2), never-smoker, moderate alcohol consumption, a high-quality diet, 7-9 hours of sleep a night, and at least 150 minutes per week of physical activity
But Ms. McCorkell noted that she herself had a healthy preinfection lifestyle but got long COVID anyway, suggesting these approaches don’t work for everyone.
“I think one reason my symptoms weren’t addressed by primary care physicians for so long is because they looked at me and saw that I was young and healthy, so they dismissed my reports as being all in my head,” she explained. “But we know now anyone can get long COVID, regardless of age, health status, or disease severity. That’s why it’s so important that primary care physicians be able to recognize symptoms.”
A version of this article first appeared on WebMD.com.
Lisa McCorkell had a mild bout of COVID-19 in March 2020. Young and healthy, she assumed that she would bounce back quickly. But when her fatigue, shortness of breath, and brain fog persisted, she realized that she most likely had long COVID.
“Back then, we as patients basically coined the term,” she said. While her first primary care provider was sympathetic, they were unsure how to treat her. After her insurance changed, she ended up with a second primary care provider who didn’t take her symptoms seriously. “They dismissed my complaints and told me they were all in my head. I didn’t seek care for a while after that.”
Ms. McCorkell’s symptoms improved after her first COVID vaccine in the spring of 2021. She also finally found a new primary care doctor she could trust. But as one of the founders of the Patient-Led Research Collaborative, a group of researchers who study long COVID, she said many doctors still don’t know the hallmark symptoms of the condition or how to treat it.
“There’s still a lack of education on what long COVID is, and the symptoms associated with it,” she said. “Many of the symptoms that occur in long COVID are symptoms of other chronic conditions, such as chronic fatigue syndrome, that are often dismissed. And even if providers believe patients and send them for a workup, many of the routine blood and imaging tests come back normal.”
The term “long COVID” emerged in May 2020. And though the condition was recognized within a few months of the start of the pandemic, doctors weren’t sure how to screen or treat it.
While knowledge has developed since then, primary care doctors are still in a tough spot. They’re often the first providers that patients turn to when they have symptoms of long COVID.
“There’s no clear algorithm to pick up long COVID – there are no definite blood tests or biomarkers, or specific things to look for on a physical exam,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center, New York. “It’s a complicated disease that can impact every organ system of the body.”
Even so, emerging research has identified a checklist of sorts that doctors should consider when a patient seeks care for what appears to be long COVID. Among them: the key systems and organs impacted by the disease, the most common symptoms, useful therapeutic options for symptom management that have been found to help people with long COVID, and the best healthy lifestyle choices that doctors can recommend to help their patients
Here’s a closer look at each of these aspects, based on research and interviews with experts, patients, and doctors.
Key systems, organs impacted
About 10% of people who are infected with COVID-19 go on to have long COVID, according to a recent study that Ms. McCorkell helped coauthor. But more than 3 years into the pandemic, much about the condition is still a mystery.
COVID is a unique virus because it can spread far and wide in a patient’s body. A December 2022 study, published in Nature, autopsied 44 people who died of COVID and found that the virus could spread throughout the body and persist, in one case as long as 230 days after symptoms started.
“We know that there are dozens of symptoms across multiple organ systems,” said Ms. McCorkell. “That makes it harder for a primary care physician to connect the dots and associate it with COVID.”
A paper published in Nature Medicine proposed one way to help guide diagnosis. It divided symptoms into four groups:
- Cardiac and renal issues such as heart palpitations, chest pain, and kidney damage
- Sleep and anxiety problems like insomnia, waking up in the middle of the night, and anxiety
- In the musculoskeletal and nervous systems: musculoskeletal pain, osteoarthritis, and problems with mental skills
- In the digestive and respiratory systems: trouble breathing, asthma, stomach pain, nausea, and vomiting
There were also specific patterns in these groups. People in the first group were more likely to be older, male, have other conditions and to have been infected during the first wave of the COVID pandemic. People in the second group were over 60% female, and were more likely to have had previous allergies or asthma. The third group was also about 60% female, and many of them already had autoimmune conditions such as rheumatoid arthritis. Members of the fourth group – also 60% female – were the least likely of all the groups to have another condition.
This research is helpful, because it gives doctors a better sense of what conditions might make a patient more likely to get long COVID, as well as specific symptoms to look out for, said Steven Flanagan, MD, a physical medicine and rehabilitation specialist at New York University Langone Medical Center who also specializes in treating patients with long COVID.
But the “challenge there, though, for health care providers is that not everyone will fall neatly into one of these categories,” he stressed.
Checklist of symptoms
Although long COVID can be confusing, doctors say there are several symptoms that appear consistently that primary care providers should look out for, that could flag long COVID.
Postexertional malaise (PEM). This is different from simply feeling tired. “This term is often conflated with fatigue, but it’s very different,” said David Putrino, PhD, director of rehabilitation innovation at the Mount Sinai Health System in New York, who says that he sees it in about 90% of patients who come to his long COVID clinic.
PEM is the worsening of symptoms after physical or mental exertion. This usually occurs a day or 2 after the activity, but it can last for days, and sometimes weeks.
“It’s very different from fatigue, which is just a generalized tiredness, and exercise intolerance, where someone complains of not being able to do their usual workout on the treadmill,” he noted. “People with PEM are able to push through and do what they need to do, and then are hit with symptoms anywhere from 12 to 72 hours later.”
Dysautonomia. This is an umbrella term used to describe a dysfunction of the autonomic nervous system, which regulates bodily functions that you can’t control, like your blood pressure, heart rate, and breathing. This can cause symptoms such as heart palpitations, along with orthostatic intolerance, which means you can’t stand up for long without feeling faint or dizzy.
“In my practice, about 80% of patients meet criteria for dysautonomia,” said Dr. Putrino. Other research has found that it’s present in about two-thirds of long COVID patients.
One relatively easy way primary care providers can diagnose dysautonomia is to do the tilt table test. This helps check for postural orthostatic tachycardia syndrome (POTS), one of the most common forms of dysautonomia. During this exam, the patient lies flat on a table. As the head of the table is raised to an almost upright position, their heart rate and blood pressure are measured. Signs of POTS include an abnormal heart rate when you’re upright, as well as a worsening of symptoms.
Exercise intolerance. A review published in the journal JAMA Network Open analyzed 38 studies on long COVID and exercise and found that patients with the condition had a much harder time doing physical activity. Exercise capacity was reduced to levels that would be expected about a decade later in life, according to study authors.
“This is especially important because it can’t be explained just by deconditioning,” said Dr. Purpura. “Sometimes these patients are encouraged to ramp up exercise as a way to help with symptoms, but in these cases, encouraging them to push through can cause postexertional malaise, which sets patients back and delays recovery.”
While long COVID can cause dozens of symptoms, a paper Ms. McCorkell coauthored zeroed in on some of the most common ones: chest pain, heart palpitations, coughing, shortness of breath, belly pain, nausea, problems with mental skills, fatigue, disordered sleep, memory loss, ringing in the ears (tinnitus), erectile dysfunction, irregular menstruation, and worsened premenstrual syndrome.
While most primary care providers are familiar with some of these long COVID symptoms, they may not be aware of others.
“COVID itself seems to cause hormonal changes that can lead to erection and menstrual cycle problems,” explained Dr. Putrino. “But these may not be picked up in a visit if the patient is complaining of other signs of long COVID.”
It’s not just what symptoms are, but when they began to occur, he added. “Usually, these symptoms either start with the initial COVID infection, or begin sometime within 3 months after the acute COVID infection. That’s why it’s important for people with COVID to take notice of anything unusual that crops up within a month or 2 after getting sick.”
Can you prevent long COVID?
You can’t, but one of the best ways to reduce your risk is to get vaccinated. Getting at least one dose of a COVID vaccine before you test positive for COVID lowers your risk of long COVID by about 35% according to a study published in Antimicrobial Stewardship & Healthcare Epidemiology. Unvaccinated people who recovered from COVID, and then got a vaccine, lowered their own long COVID risk by 27%.
In addition, a study published in JAMA Internal Medicine found that women who were infected with COVID were less likely to go on to get long COVID and/or have less debilitating symptoms if they had a healthy lifestyle, which included the following: a healthy weight (a body mass index between 18.5 and 24.7 kg/m2), never-smoker, moderate alcohol consumption, a high-quality diet, 7-9 hours of sleep a night, and at least 150 minutes per week of physical activity
But Ms. McCorkell noted that she herself had a healthy preinfection lifestyle but got long COVID anyway, suggesting these approaches don’t work for everyone.
“I think one reason my symptoms weren’t addressed by primary care physicians for so long is because they looked at me and saw that I was young and healthy, so they dismissed my reports as being all in my head,” she explained. “But we know now anyone can get long COVID, regardless of age, health status, or disease severity. That’s why it’s so important that primary care physicians be able to recognize symptoms.”
A version of this article first appeared on WebMD.com.
Single bivalent COVID booster is enough for now: CDC
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
Negative expectations of COVID shots may amplify side effects
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
FROM JAMA NETWORK OPEN
Nasal COVID treatment shows early promise against multiple variants
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
FROM NATURE COMMUNICATIONS
High-dose prophylactic anticoagulation benefits patients with COVID-19 pneumonia
High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.
Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.
Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.
However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.
In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.
The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first. The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.
The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).
The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.
For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.
However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.
The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.
The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.
However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
Results inform current clinical practice
Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.
“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.
In the current study, , a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”
The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”
Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.
The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.
Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
A version of this article originally appeared on Medscape.com.
High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.
Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.
Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.
However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.
In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.
The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first. The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.
The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).
The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.
For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.
However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.
The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.
The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.
However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
Results inform current clinical practice
Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.
“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.
In the current study, , a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”
The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”
Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.
The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.
Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
A version of this article originally appeared on Medscape.com.
High-dose prophylactic anticoagulation or therapeutic anticoagulation reduced de novo thrombosis in patients with hypoxemic COVID-19 pneumonia, based on data from 334 adults.
Patients with hypoxemic COVID-19 pneumonia are at increased risk of thrombosis and anticoagulation-related bleeding, therefore data to identify the lowest effective anticoagulant dose are needed, wrote Vincent Labbé, MD, of Sorbonne University, Paris, and colleagues.
Previous studies of different anticoagulation strategies for noncritically ill and critically ill patients with COVID-19 pneumonia have shown contrasting results, but some institutions recommend a high-dose regimen in the wake of data showing macrovascular thrombosis in patients with COVID-19 who were treated with standard anticoagulation, the authors wrote.
However, no previously published studies have compared the effectiveness of the three anticoagulation strategies: high-dose prophylactic anticoagulation (HD-PA), standard dose prophylactic anticoagulation (SD-PA), and therapeutic anticoagulation (TA), they said.
In the open-label Anticoagulation COVID-19 (ANTICOVID) trial, published in JAMA Internal Medicine, the researchers identified consecutively hospitalized adults aged 18 years and older being treated for hypoxemic COVID-19 pneumonia in 23 centers in France between April 2021 and December 2021.
The patients were randomly assigned to SD-PA (116 patients), HD-PA (111 patients), and TA (112 patients) using low-molecular-weight heparin for 14 days, or until either hospital discharge or weaning from supplemental oxygen for 48 consecutive hours, whichever outcome occurred first. The HD-PA patients received two times the SD-PA dose. The mean age of the patients was 58.3 years, and approximately two-thirds were men; race and ethnicity data were not collected. Participants had no macrovascular thrombosis at the start of the study.
The primary outcomes were all-cause mortality and time to clinical improvement (defined as the time from randomization to a 2-point improvement on a 7-category respiratory function scale).
The secondary outcome was a combination of safety and efficacy at day 28 that included a composite of thrombosis (ischemic stroke, noncerebrovascular arterial thrombosis, deep venous thrombosis, pulmonary artery thrombosis, and central venous catheter–related deep venous thrombosis), major bleeding, or all-cause death.
For the primary outcome, results were similar among the groups; HD-PA had no significant benefit over SD-PA or TA. All-cause death rates for SD-PA, HD-PA, and TA patients were 14%, 12%, and 13%, respectively. The time to clinical improvement for the three groups was approximately 8 days, 9 days, and 8 days, respectively. Results for the primary outcome were consistent across all prespecified subgroups.
However, HD-PA was associated with a significant fourfold reduced risk of de novo thrombosis compared with SD-PA (5.5% vs. 20.2%) with no observed increase in major bleeding. TA was not associated with any significant improvement in primary or secondary outcomes compared with HD-PA or SD-PA.
The current study findings of no improvement in survival or disease resolution in patients with a higher anticoagulant dose reflects data from previous studies, the researchers wrote in their discussion. “Our study results together with those of previous RCTs support the premise that the role of microvascular thrombosis in worsening organ dysfunction may be narrower than estimated,” they said.
The findings were limited by several factors including the open-label design and the relatively small sample size, the lack of data on microvascular (vs. macrovascular) thrombosis at baseline, and the predominance of the Delta variant of COVID-19 among the study participants, which may have contributed to a lower mortality rate, the researchers noted.
However, given the significant reduction in de novo thrombosis, the results support the routine use of HD-PA in patients with severe hypoxemic COVID-19 pneumonia, they concluded.
Results inform current clinical practice
Over the course of the COVID-19 pandemic, “Patients hospitalized with COVID-19 manifested the highest risk for thromboembolic complications, especially patients in the intensive care setting,” and early reports suggested that standard prophylactic doses of anticoagulant therapy might be insufficient to prevent thrombotic events, Richard C. Becker, MD, of the University of Cincinnati, and Thomas L. Ortel, MD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
“Although there have been several studies that have investigated the role of anticoagulant therapy in hospitalized patients with COVID-19, this is the first study that specifically compared a standard, prophylactic dose of low-molecular-weight heparin to a ‘high-dose’ prophylactic regimen and to a full therapeutic dose regimen,” Dr. Ortel said in an interview.
“Given the concerns about an increased thrombotic risk with prophylactic dose anticoagulation, and the potential bleeding risk associated with a full therapeutic dose of anticoagulation, this approach enabled the investigators to explore the efficacy and safety of an intermediate dose between these two extremes,” he said.
In the current study, , a finding that was not observed in other studies investigating anticoagulant therapy in hospitalized patients with severe COVID-19,” Dr. Ortel told this news organization. “Much initial concern about progression of disease in patients hospitalized with severe COVID-19 focused on the role of microvascular thrombosis, which appears to be less important in this process, or, alternatively, less responsive to anticoagulant therapy.”
The clinical takeaway from the study, Dr. Ortel said, is the decreased risk for venous thromboembolism with a high-dose prophylactic anticoagulation strategy compared with a standard-dose prophylactic regimen for patients hospitalized with hypoxemic COVID-19 pneumonia, “leading to an improved net clinical outcome.”
Looking ahead, “Additional research is needed to determine whether a higher dose of prophylactic anticoagulation would be beneficial for patients hospitalized with COVID-19 pneumonia who are not in an intensive care unit setting,” Dr. Ortel said. Studies are needed to determine whether therapeutic interventions are equally beneficial in patients with different coronavirus variants, since most patients in the current study were infected with the Delta variant, he added.
The study was supported by LEO Pharma. Dr. Labbé disclosed grants from LEO Pharma during the study and fees from AOP Health unrelated to the current study.
Dr. Becker disclosed personal fees from Novartis Data Safety Monitoring Board, Ionis Data Safety Monitoring Board, and Basking Biosciences Scientific Advisory Board unrelated to the current study. Dr. Ortel disclosed grants from the National Institutes of Health, Instrumentation Laboratory, Stago, and Siemens; contract fees from the Centers for Disease Control and Prevention; and honoraria from UpToDate unrelated to the current study.
A version of this article originally appeared on Medscape.com.
COVID-19 potentially induced adult-onset IgA vasculitis
Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.
Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.
COVID-19 has been associated with pulmonary and extrapulmonary complications, but , the authors wrote.
The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.
In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.
A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.
In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.
The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.
“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.
Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.
Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.
COVID-19 has been associated with pulmonary and extrapulmonary complications, but , the authors wrote.
The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.
In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.
A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.
In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.
The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.
“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.
Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.
Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.
COVID-19 has been associated with pulmonary and extrapulmonary complications, but , the authors wrote.
The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.
In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.
A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.
In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.
The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.
“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.
Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM CUREUS
COVID led to rise in pregnancy-related deaths: New research
The rise in deaths was most pronounced among Black mothers.
In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.
COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.
Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women.
Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:
- 20.4 for women under age 25.
- 31.3 for women ages 25 to 39.
- 138.5 for women ages 40 and older.
Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”
The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.
“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.
A version of this article first appeared on WebMD.com.
The rise in deaths was most pronounced among Black mothers.
In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.
COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.
Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women.
Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:
- 20.4 for women under age 25.
- 31.3 for women ages 25 to 39.
- 138.5 for women ages 40 and older.
Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”
The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.
“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.
A version of this article first appeared on WebMD.com.
The rise in deaths was most pronounced among Black mothers.
In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.
COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.
Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women.
Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:
- 20.4 for women under age 25.
- 31.3 for women ages 25 to 39.
- 138.5 for women ages 40 and older.
Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”
The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.
“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.
A version of this article first appeared on WebMD.com.
COVID in pregnancy may affect boys’ neurodevelopment: Study
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Boys born to mothers infected with SARS‐CoV‐2 during pregnancy may be more likely to receive a diagnosis of a neurodevelopmental disorder by age 12 months, according to new research.
Andrea G. Edlow, MD, MSc, with Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues examined data from 18,355 births between March 1, 2020, and May 31, 2021, at eight hospitals across two health systems in Massachusetts.
Of these births, 883 (4.8%) were to individuals who tested positive for SARS‐CoV‐2 during pregnancy. Among the children exposed to SARS‐CoV‐2 in the womb, 26 (3%) received a neurodevelopmental diagnosis, including disorders of motor function, speech and language, and psychological development, by age 1 year. In the group unexposed to the virus, 1.8% received such a diagnosis.
After adjusting for factors such as race, insurance, maternal age, and preterm birth, Dr. Edlow’s group found that a positive test for SARS-CoV-2 during pregnancy was associated with an increased risk for neurodevelopmental diagnoses at 12 months among boys (adjusted odds ratio, 1.94; 95% confidence interval, 1.12-3.17; P = .01), but not among girls.
In a subset of children with data available at 18 months, the correlation among boys at that age was less pronounced and not statistically significant (aOR, 1.42; 95% CI, 0.92-2.11; P = .10).
The findings were published online in JAMA Network Open
Prior epidemiological research has suggested that maternal infection during pregnancy is associated with heightened risk for a range of neurodevelopmental disorders, including autism and schizophrenia, in offspring, the authors wrote.
“The neurodevelopmental risk associated with maternal SARS-CoV-2 infection was disproportionately high in male infants, consistent with the known increased vulnerability of males in the face of prenatal adverse exposures,” Dr. Edlow said in a news release about the findings.
Larger studies and longer follow‐up are needed to confirm and reliably estimate the risk, the researchers said.
“It is not clear that the changes we can detect at 12 and 18 months will be indicative of persistent risks for disorders such as autism spectrum disorder, intellectual disability, or schizophrenia,” they write.
New data published online by the Centers for Disease Control and Prevention show that in 11 communities in 2020, 1 in 36 (2.8%) 8-year-old children had been identified with autism spectrum disorder, an increase from 2.3% in 2018. The data also show that the early months of the pandemic may have disrupted autism detection efforts among 4-year-olds.
The investigators were supported by grants from the National Institutes of Health and the Simons Foundation Autism Research Initiative. Coauthors disclosed consulting for or receiving personal fees from biotechnology and pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN