A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

Home spirometry has become increasingly used among cystic fibrosis patients during the COVID-19 pandemic, and new research suggests that home devices perform reasonably well. Forced expiratory volume in 1 second (FEV₁) values were a bit lower than values seen in clinical spirometry performed in the same patient at a nearby time point, but the procedure reliably picked up decreases in FEV₁, potentially helping patients and clinicians spot exacerbations early.

“Home spirometry was sort of a curiosity that was slowly working its way into cystic fibrosis research in 2019, and then all of a sudden in 2020 it became front and center as the only way to continue with clinical monitoring and research in many cases,” Alexander Paynter, MS, a biostatistician at the Cystic Fibrosis Foundation’s Therapeutic Development Network Coordinating Center, said during a talk at the virtual North American Cystic Fibrosis Conference.

To better determine how closely home spirometry matches clinical spirometry, Mr. Paynter and his colleagues analyzed data from the eICE study, which included 267 cystic fibrosis patients aged 14 and over at 14 cystic fibrosis centers. They were randomized to use home spirometry as an early intervention to detect exacerbations, or to continue usual clinic care with visits to the clinic every 3 months. The dataset includes twice-weekly home spirometry values, with a full-year of follow-up data. The researchers compared the home spirometry data to the clinical data closest in time to it. Clinic spirometry data with no corresponding home data within 7 days were discarded.

There was an estimated difference of –2.01 mL between home and clinic tests, with home spirometry producing lower values (95% confidence interval, –3.56 to –0.45). “There is actually a bias in home spirometry as compared to clinic spirometry,” concluded Mr. Paynter.

One explanation for lower values in home spirometry is that users are inexperienced with the device. If that’s true, then agreement should improve over time, but the researchers didn’t see strong evidence of that. Among 44 patients who completed five clinical visits, there was a difference of –2.97 (standard deviation [SD], 10.51) at baseline, –1.66 at 3 months (SD, 13.49), –3.7 at 6 months (SD, 12.44), –0.86 at 9 months (SD, 13.73), and –0.53 at 12 months (SD, 13.35). Though there was improvement over time, “we don’t find a lot of evidence that this bias completely resolves,” said Mr. Paynter.

In fact, a more likely explanation is the presence of coaching by a technician during clinical spirometry, according to Robert J. Giusti, MD, clinical professor of pediatrics and director of the Pediatric Cystic Fibrosis Center at New York University. “When they’re doing it at home, they don’t do it with the same effort, so I think that coaching through telemedicine during the home spirometry would make that difference disappear,” he said when asked to comment on the study.

SOURCE: Alex Paynter et al. NACFC 2020. Poster 643.

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

As Emily Brown stood in a food pantry looking at her options, she felt alone. Up to that point, she had never struggled financially. But there she was, desperate to find safe food for her young daughter with food allergies. What she found was a jar of salsa and some potatoes.

“That was all that was available,” said Ms. Brown, who lives in Kansas City, Kansas. “It was just a desperate place.”

When she became a parent, Ms. Brown left her job for lack of child care that would accommodate her daughter’s allergies to peanuts, tree nuts, milk, eggs, wheat, and soy. When she and her husband then turned to a federal food assistance program, they found few allowable allergy substitutions. The closest allergy support group she could find was an hour away. She was almost always the only Black parent, and the only poor parent, there.

Ms. Brown called national food allergy advocacy organizations to ask for guidance to help poor families find safe food and medical resources, but she said she was told that wasn’t their focus. Support groups, fundraising activities, and advocacy efforts, plus clinical and research outreach, were targeted at wealthier – and White – families. Advertising rarely reflected families that looked like hers. She felt unseen.

“In many ways, food allergy is an invisible disease. The burden of the disease, the activities and energy it takes to avoid allergens, are mostly invisible to those not impacted,” Ms. Brown said. “Black and other minority patients often lack voice and visibility in the health care system. Add the additional burden of an invisible condition and you are in a really vulnerable position.”

An estimated 6 million children in the United States have food allergies, 40% of them with more than one. Though limited research has been done on race and class breakdowns, recent studies show that poor children and some groups of minority children not only have a higher incidence of food allergies than White children, but their families also have more difficulty accessing appropriate child care, safe food, medical care, and lifesaving medicine like epinephrine for them.

Black children are 7% more likely to have food allergies than white children, according to a 2020 study by Dr. Ruchi Gupta, MD, at Northwestern University, Chicago. To be sure, the study shows that Asian children are 24% more likely than White children to have food allergies. But Black and Hispanic children are disproportionately more likely to live in poor communities, to have asthma, and to suffer from systemic racism in the delivery of medical care.

And finding allergen-free food to keep allergic kids safe can be costly – in both time and money.

“Many times, a mother is frank and says: ‘I have $20-$40 to buy groceries for the week, and if I buy these foods that you are telling me to buy, I will not be able to feed my entire family,’” said Carla Davis, MD, director of the food allergy program at Houston’s Texas Children’s Hospital. “If you are diagnosed with a food allergy and you don’t have disposable income or disposable time, there is really no way that you will be able to alter your diet in a way that your child is going to stay away from their allergen.”

Fed up with the lack of support, Ms. Brown founded the Food Equality Initiative advocacy organization in 2014. It offers an online marketplace to income-eligible families in Kansas and Missouri who, with a doctor’s note about the allergy, can order free allergy-safe food to fit their needs.

Nationwide, though, families’ needs far outstrip what her group can offer – and the problem has gotten worse amid the economic squeeze of the COVID pandemic. Job losses and business closures have exacerbated the barriers to finding and affording nutritious food, according to a report from Feeding America, an association of food banks.

Ms. Brown said her organization more than doubled its clientele in March through August, compared with the same period in 2019. And though it currently serves only Missouri and Kansas, she said the organization has been fielding an increasing number of calls from across the country since the pandemic began.

For low-income minorities, who live disproportionately in food deserts, fresh and allergy-friendly foods can be especially expensive and difficult to find in the best of times.

Food assistance programs are heavily weighted to prepackaged and processed foods, which often include the very ingredients that are problematic. Black children are more likely to be allergic to wheat and soy than White children, and both Black and Hispanic children are more likely to be allergic to corn, shellfish, and fish, according to a 2016 study.

Some programs allow few allergy substitutions. For example, the federal Special Supplemental Nutrition Program for Women, Infants, and Children allows only canned beans as a substitute for peanut butter. While nutritionally similar, beans are not as easy to pack for a kid’s lunch. Ms. Brown questions why WIC won’t allow a seed butter, such as sunflower butter, instead. She said they are nutritionally and functionally similar and are offered as allergy substitutions in other food programs.

Making matters worse, low-income households pay more than twice as much as higher-income families for the emergency medical care their children receive for their allergies, according to a 2016 study by Dr. Gupta. The kids often arrive at the hospital in more distress because they lack safe food and allergy medications – and because asthma, which disproportionately hits Black and Puerto Rican children and low-income communities, complicates allergic reactions.

“So, in these vulnerable populations, it’s like a double whammy, and we see that reflected in the data,” said Lakiea Wright-Bello, MD, a medical director in specialty diagnostics at Thermo Fisher Scientific and an allergist at Brigham and Women’s Hospital in Boston.

Thomas and Dina Silvera, who are Black and Latina, lived this horror firsthand. After their 3-year-old son, Elijah-Alavi, died as a result of a dairy allergy when fed a grilled cheese instead of his allergen-free food at his preschool, they launched the Elijah-Alavi Foundation to address the dearth of information about food allergies and the critical lack of culturally sensitive medical care in low-income communities.

“We started it for a cause, not because we wanted to, but because we had to,” said Thomas Silvera. “Our main focus is to bring to underserved communities – especially communities of color – this information at no cost to them.”

Recently, other advocacy groups, including Food Allergy Research & Education, a national advocacy organization, also have started to turn their attention to a lack of access and support in poor and minority communities. When Lisa Gable, who is White, took over at the group known as FARE in 2018, she began to diversify the organization internally and to make it more inclusive.

“There wasn’t a big tent when I walked in the door,” said Ms. Gable. “What we have been focused on doing is trying to find partners and relationships that will allow us to diversify those engaged in the community, because it has not been a diverse community.”

FARE has funded research into the cost of food allergies. It is also expanding its patient registry, which collects data for research, as well as its clinical network of medical institutions to include more diverse communities.

Dr. Gupta is now leading one of the first studies funded by the National Institutes of Health to investigate food allergy in children by race and ethnicity. It looks at all aspects of food allergies, including family life, management, access to care, and genetics.

“That’s a big deal,” said Dr. Gupta. “Because if we really want to improve food allergy management, care and understanding, we really need to understand how it impacts different groups. And that hasn’t been done.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

As Emily Brown stood in a food pantry looking at her options, she felt alone. Up to that point, she had never struggled financially. But there she was, desperate to find safe food for her young daughter with food allergies. What she found was a jar of salsa and some potatoes.

“That was all that was available,” said Ms. Brown, who lives in Kansas City, Kansas. “It was just a desperate place.”

When she became a parent, Ms. Brown left her job for lack of child care that would accommodate her daughter’s allergies to peanuts, tree nuts, milk, eggs, wheat, and soy. When she and her husband then turned to a federal food assistance program, they found few allowable allergy substitutions. The closest allergy support group she could find was an hour away. She was almost always the only Black parent, and the only poor parent, there.

Ms. Brown called national food allergy advocacy organizations to ask for guidance to help poor families find safe food and medical resources, but she said she was told that wasn’t their focus. Support groups, fundraising activities, and advocacy efforts, plus clinical and research outreach, were targeted at wealthier – and White – families. Advertising rarely reflected families that looked like hers. She felt unseen.

“In many ways, food allergy is an invisible disease. The burden of the disease, the activities and energy it takes to avoid allergens, are mostly invisible to those not impacted,” Ms. Brown said. “Black and other minority patients often lack voice and visibility in the health care system. Add the additional burden of an invisible condition and you are in a really vulnerable position.”

An estimated 6 million children in the United States have food allergies, 40% of them with more than one. Though limited research has been done on race and class breakdowns, recent studies show that poor children and some groups of minority children not only have a higher incidence of food allergies than White children, but their families also have more difficulty accessing appropriate child care, safe food, medical care, and lifesaving medicine like epinephrine for them.

Black children are 7% more likely to have food allergies than white children, according to a 2020 study by Dr. Ruchi Gupta, MD, at Northwestern University, Chicago. To be sure, the study shows that Asian children are 24% more likely than White children to have food allergies. But Black and Hispanic children are disproportionately more likely to live in poor communities, to have asthma, and to suffer from systemic racism in the delivery of medical care.

And finding allergen-free food to keep allergic kids safe can be costly – in both time and money.

“Many times, a mother is frank and says: ‘I have $20-$40 to buy groceries for the week, and if I buy these foods that you are telling me to buy, I will not be able to feed my entire family,’” said Carla Davis, MD, director of the food allergy program at Houston’s Texas Children’s Hospital. “If you are diagnosed with a food allergy and you don’t have disposable income or disposable time, there is really no way that you will be able to alter your diet in a way that your child is going to stay away from their allergen.”

Fed up with the lack of support, Ms. Brown founded the Food Equality Initiative advocacy organization in 2014. It offers an online marketplace to income-eligible families in Kansas and Missouri who, with a doctor’s note about the allergy, can order free allergy-safe food to fit their needs.

Nationwide, though, families’ needs far outstrip what her group can offer – and the problem has gotten worse amid the economic squeeze of the COVID pandemic. Job losses and business closures have exacerbated the barriers to finding and affording nutritious food, according to a report from Feeding America, an association of food banks.

Ms. Brown said her organization more than doubled its clientele in March through August, compared with the same period in 2019. And though it currently serves only Missouri and Kansas, she said the organization has been fielding an increasing number of calls from across the country since the pandemic began.

For low-income minorities, who live disproportionately in food deserts, fresh and allergy-friendly foods can be especially expensive and difficult to find in the best of times.

Food assistance programs are heavily weighted to prepackaged and processed foods, which often include the very ingredients that are problematic. Black children are more likely to be allergic to wheat and soy than White children, and both Black and Hispanic children are more likely to be allergic to corn, shellfish, and fish, according to a 2016 study.

Some programs allow few allergy substitutions. For example, the federal Special Supplemental Nutrition Program for Women, Infants, and Children allows only canned beans as a substitute for peanut butter. While nutritionally similar, beans are not as easy to pack for a kid’s lunch. Ms. Brown questions why WIC won’t allow a seed butter, such as sunflower butter, instead. She said they are nutritionally and functionally similar and are offered as allergy substitutions in other food programs.

Making matters worse, low-income households pay more than twice as much as higher-income families for the emergency medical care their children receive for their allergies, according to a 2016 study by Dr. Gupta. The kids often arrive at the hospital in more distress because they lack safe food and allergy medications – and because asthma, which disproportionately hits Black and Puerto Rican children and low-income communities, complicates allergic reactions.

“So, in these vulnerable populations, it’s like a double whammy, and we see that reflected in the data,” said Lakiea Wright-Bello, MD, a medical director in specialty diagnostics at Thermo Fisher Scientific and an allergist at Brigham and Women’s Hospital in Boston.

Thomas and Dina Silvera, who are Black and Latina, lived this horror firsthand. After their 3-year-old son, Elijah-Alavi, died as a result of a dairy allergy when fed a grilled cheese instead of his allergen-free food at his preschool, they launched the Elijah-Alavi Foundation to address the dearth of information about food allergies and the critical lack of culturally sensitive medical care in low-income communities.

“We started it for a cause, not because we wanted to, but because we had to,” said Thomas Silvera. “Our main focus is to bring to underserved communities – especially communities of color – this information at no cost to them.”

Recently, other advocacy groups, including Food Allergy Research & Education, a national advocacy organization, also have started to turn their attention to a lack of access and support in poor and minority communities. When Lisa Gable, who is White, took over at the group known as FARE in 2018, she began to diversify the organization internally and to make it more inclusive.

“There wasn’t a big tent when I walked in the door,” said Ms. Gable. “What we have been focused on doing is trying to find partners and relationships that will allow us to diversify those engaged in the community, because it has not been a diverse community.”

FARE has funded research into the cost of food allergies. It is also expanding its patient registry, which collects data for research, as well as its clinical network of medical institutions to include more diverse communities.

Dr. Gupta is now leading one of the first studies funded by the National Institutes of Health to investigate food allergy in children by race and ethnicity. It looks at all aspects of food allergies, including family life, management, access to care, and genetics.

“That’s a big deal,” said Dr. Gupta. “Because if we really want to improve food allergy management, care and understanding, we really need to understand how it impacts different groups. And that hasn’t been done.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

As Emily Brown stood in a food pantry looking at her options, she felt alone. Up to that point, she had never struggled financially. But there she was, desperate to find safe food for her young daughter with food allergies. What she found was a jar of salsa and some potatoes.

“That was all that was available,” said Ms. Brown, who lives in Kansas City, Kansas. “It was just a desperate place.”

When she became a parent, Ms. Brown left her job for lack of child care that would accommodate her daughter’s allergies to peanuts, tree nuts, milk, eggs, wheat, and soy. When she and her husband then turned to a federal food assistance program, they found few allowable allergy substitutions. The closest allergy support group she could find was an hour away. She was almost always the only Black parent, and the only poor parent, there.

Ms. Brown called national food allergy advocacy organizations to ask for guidance to help poor families find safe food and medical resources, but she said she was told that wasn’t their focus. Support groups, fundraising activities, and advocacy efforts, plus clinical and research outreach, were targeted at wealthier – and White – families. Advertising rarely reflected families that looked like hers. She felt unseen.

“In many ways, food allergy is an invisible disease. The burden of the disease, the activities and energy it takes to avoid allergens, are mostly invisible to those not impacted,” Ms. Brown said. “Black and other minority patients often lack voice and visibility in the health care system. Add the additional burden of an invisible condition and you are in a really vulnerable position.”

An estimated 6 million children in the United States have food allergies, 40% of them with more than one. Though limited research has been done on race and class breakdowns, recent studies show that poor children and some groups of minority children not only have a higher incidence of food allergies than White children, but their families also have more difficulty accessing appropriate child care, safe food, medical care, and lifesaving medicine like epinephrine for them.

Black children are 7% more likely to have food allergies than white children, according to a 2020 study by Dr. Ruchi Gupta, MD, at Northwestern University, Chicago. To be sure, the study shows that Asian children are 24% more likely than White children to have food allergies. But Black and Hispanic children are disproportionately more likely to live in poor communities, to have asthma, and to suffer from systemic racism in the delivery of medical care.

And finding allergen-free food to keep allergic kids safe can be costly – in both time and money.

“Many times, a mother is frank and says: ‘I have $20-$40 to buy groceries for the week, and if I buy these foods that you are telling me to buy, I will not be able to feed my entire family,’” said Carla Davis, MD, director of the food allergy program at Houston’s Texas Children’s Hospital. “If you are diagnosed with a food allergy and you don’t have disposable income or disposable time, there is really no way that you will be able to alter your diet in a way that your child is going to stay away from their allergen.”

Fed up with the lack of support, Ms. Brown founded the Food Equality Initiative advocacy organization in 2014. It offers an online marketplace to income-eligible families in Kansas and Missouri who, with a doctor’s note about the allergy, can order free allergy-safe food to fit their needs.

Nationwide, though, families’ needs far outstrip what her group can offer – and the problem has gotten worse amid the economic squeeze of the COVID pandemic. Job losses and business closures have exacerbated the barriers to finding and affording nutritious food, according to a report from Feeding America, an association of food banks.

Ms. Brown said her organization more than doubled its clientele in March through August, compared with the same period in 2019. And though it currently serves only Missouri and Kansas, she said the organization has been fielding an increasing number of calls from across the country since the pandemic began.

For low-income minorities, who live disproportionately in food deserts, fresh and allergy-friendly foods can be especially expensive and difficult to find in the best of times.

Food assistance programs are heavily weighted to prepackaged and processed foods, which often include the very ingredients that are problematic. Black children are more likely to be allergic to wheat and soy than White children, and both Black and Hispanic children are more likely to be allergic to corn, shellfish, and fish, according to a 2016 study.

Some programs allow few allergy substitutions. For example, the federal Special Supplemental Nutrition Program for Women, Infants, and Children allows only canned beans as a substitute for peanut butter. While nutritionally similar, beans are not as easy to pack for a kid’s lunch. Ms. Brown questions why WIC won’t allow a seed butter, such as sunflower butter, instead. She said they are nutritionally and functionally similar and are offered as allergy substitutions in other food programs.

Making matters worse, low-income households pay more than twice as much as higher-income families for the emergency medical care their children receive for their allergies, according to a 2016 study by Dr. Gupta. The kids often arrive at the hospital in more distress because they lack safe food and allergy medications – and because asthma, which disproportionately hits Black and Puerto Rican children and low-income communities, complicates allergic reactions.

“So, in these vulnerable populations, it’s like a double whammy, and we see that reflected in the data,” said Lakiea Wright-Bello, MD, a medical director in specialty diagnostics at Thermo Fisher Scientific and an allergist at Brigham and Women’s Hospital in Boston.

Thomas and Dina Silvera, who are Black and Latina, lived this horror firsthand. After their 3-year-old son, Elijah-Alavi, died as a result of a dairy allergy when fed a grilled cheese instead of his allergen-free food at his preschool, they launched the Elijah-Alavi Foundation to address the dearth of information about food allergies and the critical lack of culturally sensitive medical care in low-income communities.

“We started it for a cause, not because we wanted to, but because we had to,” said Thomas Silvera. “Our main focus is to bring to underserved communities – especially communities of color – this information at no cost to them.”

Recently, other advocacy groups, including Food Allergy Research & Education, a national advocacy organization, also have started to turn their attention to a lack of access and support in poor and minority communities. When Lisa Gable, who is White, took over at the group known as FARE in 2018, she began to diversify the organization internally and to make it more inclusive.

“There wasn’t a big tent when I walked in the door,” said Ms. Gable. “What we have been focused on doing is trying to find partners and relationships that will allow us to diversify those engaged in the community, because it has not been a diverse community.”

FARE has funded research into the cost of food allergies. It is also expanding its patient registry, which collects data for research, as well as its clinical network of medical institutions to include more diverse communities.

Dr. Gupta is now leading one of the first studies funded by the National Institutes of Health to investigate food allergy in children by race and ethnicity. It looks at all aspects of food allergies, including family life, management, access to care, and genetics.

“That’s a big deal,” said Dr. Gupta. “Because if we really want to improve food allergy management, care and understanding, we really need to understand how it impacts different groups. And that hasn’t been done.”

KHN (Kaiser Health News) is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at [email protected].

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at [email protected].

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at [email protected].

As we navigate a time unlike any other, it is clear that the value hospitalists provide is growing stronger as the hospital medicine field expands. Many Society of Hospital Medicine members look to its Fellows program as a worthwhile opportunity to distinguish themselves as leaders in the field and accelerate their careers in the specialty.

An active member of SHM since 2012 and member of its 2020 class of Fellows, Tanisha Hamilton, MD, FHM, is one of these ambitious individuals.

Dr. Hamilton is based at Baylor University Medical Center in Dallas, an affiliate of Baylor Scott & White Health. Known for personalized health and wellness care, Dr. Hamilton has more than 14 years of experience in the medical field.

Her love for the hospital medicine specialty is rooted in its diversity and complexity of patient cases – something that she knew would innately complement her personality. She says that an invaluable aspect of working in the field is the ability to interact and connect with people from all walks of life.

“My patients keep me motivated in this space. Learning from my patients and having the responsibility of serving as their advocate is incredibly rewarding,” Dr. Hamilton said. “I hope my patients feel like I’ve helped to make a difference in their lives, if only for just a moment.”

When reflecting on why she joined SHM 8 years ago, Dr. Hamilton said she was encouraged to do so because of its like-minded membership community and professional development opportunities, including the Fellows program.

“I applied to SHM’s Fellows program because I’m committed to the specialty. Hospital medicine is an ever-changing field loaded with opportunities to enhance personal and professional career growth,” said Dr. Hamilton. “To me, SHM’s Fellow in Hospital Medicine [FHM] designation demonstrates the ability to make a contribution to the field and to be an instrument for change.”

She credits receiving her designation as a distinction that has opened doors to other career-enhancing opportunities and networking resources, including an expansive global community, program development at her institution, and positions within SHM. Since earning her FHM designation, Dr. Hamilton has become an engaged member of the annual meeting committee and the North Central Texas Chapter.

“Since we are taking our annual conference virtual for SHM Converge in 2021, I’m excited to see how we can transform a meeting of more than 5,000 attendees into a full digital experience with interactive workshops, exhibits, research competitions, and more,” Dr. Hamilton said. “It’s certainly going to be a challenge, but I know that our meetings department and annual conference committee will make it a success!”

As Dr. Hamilton looks forward in her hospital medicine career, she is committed to making a positive impact on the field and for her patients.

In the future, Dr. Hamilton hopes to share curriculum she recently developed and sponsored around diversity, equity, and inclusion with her team at Baylor University Medical Center.

“Following the tragic deaths of numerous individuals, including Breonna Taylor, Ahmaud Abery, and George Floyd, and other people of color who have died because of COVID-19, I have felt compelled to educate my colleagues on how to curtail systemic racism, sexism, religious discrimination, and xenophobia in health care,” Dr. Hamilton said. “This curriculum includes courses on health disparities and cultural competencies, launching a lecture series, and other educational components.”

While 2020 has been a trying year, Dr. Hamilton remains hopeful for a prosperous future.

“When I think of the future of hospital medicine, I am hopeful that hospitalists will have a more prominent role in changing the direction of our health care system,” she said. “The pandemic has made the world realize the importance of hospital medicine. We, as hospitalists, are a critical part of its infrastructure and its success.”

If you would like to join Dr. Hamilton and other like-minded hospital medicine leaders in accelerating your career, SHM is currently recruiting for the Fellows and Senior Fellows class of 2021. Applications are open until Nov. 20, 2020. These designations are available across a variety of membership categories, including physicians, nurse practitioners, physician assistants, and qualified practice administrators. Dedicated to promoting excellence, innovation, and quality improvement in patient care, Fellows designations provide members with a distinguishing credential as established pioneers in the industry.

For more information and to review your eligibility, visit hospitalmedicine.org/fellows.

Ms. Cowan is a communications specialist at the Society of Hospital Medicine.

As we navigate a time unlike any other, it is clear that the value hospitalists provide is growing stronger as the hospital medicine field expands. Many Society of Hospital Medicine members look to its Fellows program as a worthwhile opportunity to distinguish themselves as leaders in the field and accelerate their careers in the specialty.

An active member of SHM since 2012 and member of its 2020 class of Fellows, Tanisha Hamilton, MD, FHM, is one of these ambitious individuals.

Dr. Hamilton is based at Baylor University Medical Center in Dallas, an affiliate of Baylor Scott & White Health. Known for personalized health and wellness care, Dr. Hamilton has more than 14 years of experience in the medical field.

Her love for the hospital medicine specialty is rooted in its diversity and complexity of patient cases – something that she knew would innately complement her personality. She says that an invaluable aspect of working in the field is the ability to interact and connect with people from all walks of life.

“My patients keep me motivated in this space. Learning from my patients and having the responsibility of serving as their advocate is incredibly rewarding,” Dr. Hamilton said. “I hope my patients feel like I’ve helped to make a difference in their lives, if only for just a moment.”

When reflecting on why she joined SHM 8 years ago, Dr. Hamilton said she was encouraged to do so because of its like-minded membership community and professional development opportunities, including the Fellows program.

“I applied to SHM’s Fellows program because I’m committed to the specialty. Hospital medicine is an ever-changing field loaded with opportunities to enhance personal and professional career growth,” said Dr. Hamilton. “To me, SHM’s Fellow in Hospital Medicine [FHM] designation demonstrates the ability to make a contribution to the field and to be an instrument for change.”

She credits receiving her designation as a distinction that has opened doors to other career-enhancing opportunities and networking resources, including an expansive global community, program development at her institution, and positions within SHM. Since earning her FHM designation, Dr. Hamilton has become an engaged member of the annual meeting committee and the North Central Texas Chapter.

“Since we are taking our annual conference virtual for SHM Converge in 2021, I’m excited to see how we can transform a meeting of more than 5,000 attendees into a full digital experience with interactive workshops, exhibits, research competitions, and more,” Dr. Hamilton said. “It’s certainly going to be a challenge, but I know that our meetings department and annual conference committee will make it a success!”

As Dr. Hamilton looks forward in her hospital medicine career, she is committed to making a positive impact on the field and for her patients.

In the future, Dr. Hamilton hopes to share curriculum she recently developed and sponsored around diversity, equity, and inclusion with her team at Baylor University Medical Center.

“Following the tragic deaths of numerous individuals, including Breonna Taylor, Ahmaud Abery, and George Floyd, and other people of color who have died because of COVID-19, I have felt compelled to educate my colleagues on how to curtail systemic racism, sexism, religious discrimination, and xenophobia in health care,” Dr. Hamilton said. “This curriculum includes courses on health disparities and cultural competencies, launching a lecture series, and other educational components.”

While 2020 has been a trying year, Dr. Hamilton remains hopeful for a prosperous future.

“When I think of the future of hospital medicine, I am hopeful that hospitalists will have a more prominent role in changing the direction of our health care system,” she said. “The pandemic has made the world realize the importance of hospital medicine. We, as hospitalists, are a critical part of its infrastructure and its success.”

If you would like to join Dr. Hamilton and other like-minded hospital medicine leaders in accelerating your career, SHM is currently recruiting for the Fellows and Senior Fellows class of 2021. Applications are open until Nov. 20, 2020. These designations are available across a variety of membership categories, including physicians, nurse practitioners, physician assistants, and qualified practice administrators. Dedicated to promoting excellence, innovation, and quality improvement in patient care, Fellows designations provide members with a distinguishing credential as established pioneers in the industry.

For more information and to review your eligibility, visit hospitalmedicine.org/fellows.

Ms. Cowan is a communications specialist at the Society of Hospital Medicine.

As we navigate a time unlike any other, it is clear that the value hospitalists provide is growing stronger as the hospital medicine field expands. Many Society of Hospital Medicine members look to its Fellows program as a worthwhile opportunity to distinguish themselves as leaders in the field and accelerate their careers in the specialty.

An active member of SHM since 2012 and member of its 2020 class of Fellows, Tanisha Hamilton, MD, FHM, is one of these ambitious individuals.

Dr. Hamilton is based at Baylor University Medical Center in Dallas, an affiliate of Baylor Scott & White Health. Known for personalized health and wellness care, Dr. Hamilton has more than 14 years of experience in the medical field.

Her love for the hospital medicine specialty is rooted in its diversity and complexity of patient cases – something that she knew would innately complement her personality. She says that an invaluable aspect of working in the field is the ability to interact and connect with people from all walks of life.

“My patients keep me motivated in this space. Learning from my patients and having the responsibility of serving as their advocate is incredibly rewarding,” Dr. Hamilton said. “I hope my patients feel like I’ve helped to make a difference in their lives, if only for just a moment.”

When reflecting on why she joined SHM 8 years ago, Dr. Hamilton said she was encouraged to do so because of its like-minded membership community and professional development opportunities, including the Fellows program.

“I applied to SHM’s Fellows program because I’m committed to the specialty. Hospital medicine is an ever-changing field loaded with opportunities to enhance personal and professional career growth,” said Dr. Hamilton. “To me, SHM’s Fellow in Hospital Medicine [FHM] designation demonstrates the ability to make a contribution to the field and to be an instrument for change.”

She credits receiving her designation as a distinction that has opened doors to other career-enhancing opportunities and networking resources, including an expansive global community, program development at her institution, and positions within SHM. Since earning her FHM designation, Dr. Hamilton has become an engaged member of the annual meeting committee and the North Central Texas Chapter.

“Since we are taking our annual conference virtual for SHM Converge in 2021, I’m excited to see how we can transform a meeting of more than 5,000 attendees into a full digital experience with interactive workshops, exhibits, research competitions, and more,” Dr. Hamilton said. “It’s certainly going to be a challenge, but I know that our meetings department and annual conference committee will make it a success!”

As Dr. Hamilton looks forward in her hospital medicine career, she is committed to making a positive impact on the field and for her patients.

In the future, Dr. Hamilton hopes to share curriculum she recently developed and sponsored around diversity, equity, and inclusion with her team at Baylor University Medical Center.

“Following the tragic deaths of numerous individuals, including Breonna Taylor, Ahmaud Abery, and George Floyd, and other people of color who have died because of COVID-19, I have felt compelled to educate my colleagues on how to curtail systemic racism, sexism, religious discrimination, and xenophobia in health care,” Dr. Hamilton said. “This curriculum includes courses on health disparities and cultural competencies, launching a lecture series, and other educational components.”

While 2020 has been a trying year, Dr. Hamilton remains hopeful for a prosperous future.

“When I think of the future of hospital medicine, I am hopeful that hospitalists will have a more prominent role in changing the direction of our health care system,” she said. “The pandemic has made the world realize the importance of hospital medicine. We, as hospitalists, are a critical part of its infrastructure and its success.”

If you would like to join Dr. Hamilton and other like-minded hospital medicine leaders in accelerating your career, SHM is currently recruiting for the Fellows and Senior Fellows class of 2021. Applications are open until Nov. 20, 2020. These designations are available across a variety of membership categories, including physicians, nurse practitioners, physician assistants, and qualified practice administrators. Dedicated to promoting excellence, innovation, and quality improvement in patient care, Fellows designations provide members with a distinguishing credential as established pioneers in the industry.

For more information and to review your eligibility, visit hospitalmedicine.org/fellows.

Ms. Cowan is a communications specialist at the Society of Hospital Medicine.

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.