COVID-19 Updates

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

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

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

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

LONDON – Case numbers of acute hepatitis in children show “a declining trajectory,” and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

Philippa Easterbrook, MD, medical expert at the World Health Organization Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

“It’s important to remember that this includes new cases, as well as retrospectively identified cases,” Dr.Easterbrook said. “Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom.”

Data from Europe and the United States show a declining trajectory of reports of new cases. “This is a positive development,” she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

“Together the United Kingdom and the United States make up 65% of the global total,” she said.

Dr. Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.
 

Possible post-COVID phenomenon, adenovirus most commonly reported

Dr. Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

“Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that’s been reported, often 1-2 months after COVID, causing widespread organ damage?” But she pointed out that the reported COVID cases with hepatitis “don’t seem to fit these features.”

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

“There are quite high rates of detection, but they’re not in all cases. There does seem to be a high rate of detection in the younger age groups and in those who are developing severe disease, so perhaps there is some link to severity,” Dr. Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. “These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses.”

Dr. Easterbrook highlighted the importance of procuring global data, especially given that two countries are reporting the majority of cases and in high numbers. “It’s a mixed picture with different rates of adenovirus detection and of COVID,” she said. “We need good-quality data collected in a standardized way.” WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency as an example of this. “There’s only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the U.K. and the UKHSA.”

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case-control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared with other hospitalized children at the same time. “This aims to really tease out whether adenovirus is a cause or just a bystander,” she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Dr. Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.
 

Acute hepatitis is not new, but high caseload is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona.

Dr. Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

“We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients,” Dr. Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Dr. Easterbrook and Dr. Buti have disclosed no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

COVID-19 has been associated with a threefold increased risk of Alzheimer’s disease and a doubling of Parkinson’s disease risk, a new study suggests. However, the research also showed there was no excess risk of these neurologic disorders following COVID than other respiratory infections such as influenza or community-acquired bacterial pneumonia.

Considering these results, study investigator Pardis Zarifkar, MD, department of neurology, Rigshospitalet, Copenhagen University Hospital, urged doctors to “keep an eye on” COVID patients and use “a critical mindset” if these patients present with neurologic issues.

“They should consider whether the patient’s condition is something new or if there were already signs and symptoms before they had COVID-19,” she said.

The findings were presented at the 2022 congress of the European Academy of Neurology and published online in Frontiers in Neurology.

‘Surprising’ increased risk

Previous research shows more than 80% of patients hospitalized with COVID-19 have neurologic symptoms including anosmia, dysgeusia, headache, dizziness, memory and concentration difficulties, fatigue, and irritability.

However, it’s unclear whether COVID-19 affects the risk for specific neurologic diseases and if so, whether this association differs from other respiratory infections.

From electronic health records covering about half the Danish population, researchers identified adults who were tested for COVID-19 or diagnosed with community-acquired bacterial pneumonia from February 2020 to November 2021. They also flagged individuals with influenza in the corresponding prepandemic period (February 2018–November 2019).

Dr. Zarifkar noted influenza A or B and community-acquired bacterial pneumonia are two of the most common respiratory tract infections.

The investigators tracked neurologic diseases up to 12 months after a positive test. They looked at two neurodegenerative diseases, Alzheimer’s disease and Parkinson’s disease, as well as cerebrovascular disorders including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The study included 43,262 individuals with a positive COVID test without a history of influenza A/B in the past year and 876,356 without a positive COVID test. It also included 1,474 individuals with community-acquired pneumonia without a history of COVID and 8,102 with influenza A or B.

“We wanted to investigate whether COVID-19 is really that much worse than all these other common respiratory infections that we have had for ages and see every single year,” said Dr. Zarifkar.

After 12 months, the relative risk for Alzheimer’s disease was 3.4 (95% confidence interval, 2.3-5.1) in the COVID-positive group versus the COVID-negative group. The risks were greater among inpatients versus outpatients.

These results were rather unexpected, said Dr. Zarifkar. “I would have expected a small increase, but the extent of the increase was quite surprising.”

However, there was no difference when comparing the COVID-19 group with the influenza or bacterial pneumonia groups, which Dr. Zarifkar said was “very reassuring.”

The findings were similar for Parkinson’s disease, where there was a 2.2-fold increased risk of a Parkinson’s disease diagnosis within the first 12 months in COVID-positive individuals, compared with COVID-negative people (RR, 2.2; 95% CI, 1.5-3.4). Again, there was no excess risk, compared with influenza or bacterial pneumonia.

Potential mechanisms

Dr. Zarifkar believes a “constellation” of factors may explain higher risks of these diagnoses in COVID patients. Part of it could be a result of neuroinflammation, which can lead to a toxic accumulation of beta amyloid in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.

“It can accelerate a neurodegenerative disease already in the making,” she said. But perhaps the biggest driver of differences between the groups is the “scientific focus” on COVID patients. “In Denmark, almost everyone who has had COVID-19, especially severe COVID-19, is offered some sort of cognitive testing, and if you hand out MoCAs [Montreal Cognitive Assessments] which is the cognitive test we use, to almost everyone you’re meeting, you’re going to catch these disorders earlier than you might have otherwise.”

As for cerebrovascular disorders, the study showed an increased risk of ischemic stroke in COVID-positive versus COVID-negative subjects at 12 months (RR, 2.87; 95% confidence interval, 2.2-3.2).

The relatively strong inflammatory response associated with COVID-19, which may create a hypercoagulable state, may help explain the increased ischemic stroke risk in COVID patients, said Dr. Zarifkar.

The study did not show an increased risk for subarachnoid hemorrhage in COVID-positive, compared with COVID-negative, subjects but did reveal an increased risk of intracerebral hemorrhage after 12 months (RR, 4.8; 95% CI, 1.8-12.9).

This could be explained by COVID-positive subjects having a higher risk for ischemic stroke and receiving thrombolysis that may increase risk for bleeding in the brain. However, an analysis accounting for medication use found differences in thrombolysis rates didn’t change the result, said Dr. Zarifkar.

It’s also possible that extracorporeal membrane oxygenation and mechanical ventilation – interventions more frequently used in COVID-19 patients – may increase the risk for bleeding in brain, she added.

The researchers did not find an increased risk for multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome, or narcolepsy in COVID patients. However, Dr. Zarifkar noted that it can take years to detect an association with autoimmune disorders.

The investigators did not stratify risk by disease severity, although this would be an important step, she said. “The threshold of being admitted to the hospital with COVID-19 has been much lower than for influenza or bacterial pneumonia where you’re typically quite ill before you’re admitted, so this might actually dilute the findings and underestimate our findings.”

A national, registry-based study that includes the entire Danish population and additional information on vaccination status, virus variants, socioeconomic status, and comorbidities is needed, said Dr. Zarifkar.

The study was supported by Lundbeck Foundation and Novo Nordisk. Dr. Zarifkar reported no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

Contrary to previous research findings, the stress of the COVID-19 pandemic has been linked to an increased headache burden in teens.

Investigators found factors contributing to headache for preteens and teens during the pandemic included increased screen time for online learning, depression, anxiety, female sex, and weight gain.

“The stressors and pressures of the pandemic may have eventually taken their toll,” lead author Ayşe Nur Özdağ Acarli, MD, Ermenek State Hospital, department of neurology, Karaman, Turkey, told this news organization.

“Limiting screen time and providing more psychosocial supports would help lessen the burden of the COVID-19 pandemic on adolescents with headache.”

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2022.
 

Most common neurological problem in kids

Headache is the most common neurological problem in children and adolescents. Potential factors contributing to headache in this population include lack of sleep and physical activity, mental health problems, and socioeconomic conditions.

The COVID-19 pandemic has had a “striking” impact on every aspect of life for young people, said Dr. Acarli.

Some studies reported an improvement in headache prevalence among adolescents during COVID-19, which was attributed to less school-related stress. However, said Dr. Acarli in her personal clinical experience, young patients suffered more frequent and severe headaches during the pandemic.

She noted previous research examining the impact of the pandemic on headache in youth was conducted only in the early days of the pandemic and examined shorter-term effects. Research examining the long-term effects of the pandemic on headache in this patient population has been “lacking,” she said.

The study included 851 participants aged 10-18 years (mean age 14.9 years and 62% female) who were seen at a neurology or pediatric outpatient clinic from August-December 2021. The study excluded subjects with neurological problems, intellectual deficits, autism spectrum disorder, and epilepsy.

Participants completed detailed questionnaires providing data on demographics, exposure to COVID-19, and electronics, as well as information on depressive symptoms as assessed by the Patient Health Questionnaire-9 and anxiety symptoms using the Generalized Anxiety Disorder-7 and COVID-related anxiety.

“We used two distinct scales for anxiety: one for generalized anxiety and the other for COVID-related anxiety,” said Dr. Acarli.

Of the total study population, 756 (89%) reported headaches. This headache prevalence in children and adolescents is like that found in other studies.

Dr. Acarli noted several differences in the headache group versus the non-headache group. The female/male ratio was 2:1 versus 1:1, the mean age was 15.0 versus 14.4, and depression and generalized anxiety scores were significantly higher. There was no significant difference in COVID-19 history in those with and without headache.

Researchers categorized those with headache into four groups: worsening headaches (27%), improved headaches (3%), new onset headaches (10%), and stable headaches (61%).

Compared with the other groups, the worsened headache group included significantly more females and older individuals with more severe and frequent headaches. This group also had more participants reporting at least 15 headache attacks a month and using painkillers at least once a month.

The study showed headache severity was significantly increased with age, headache duration, depression, generalized anxiety (all P < .001), and COVID-19 anxiety (P < .01). Headache frequency, measured as attacks per month, was significantly increased with age, depression, and generalized anxiety (all P < .001).

Worsening headache outcomes during the pandemic were associated with longer exposure to computer screens (odds ratio, 1.7; 95% confidence interval, 1.2-2.3; P < .01), lack of suitable conditions for online learning (OR, 2.6; 95% CI, 1.8-3.8; P < .001), depression (OR, 2.0; 95% CI, 1.4-2.8; P < .001); and COVID-19 anxiety (OR, 3.2; 95% CI, 1.3-8.0; P < .01). Other contributing factors included school exams, living in a city, female sex, and weight gain.

There may be a link between COVID-related headaches and anxiety or depression, but it’s unclear what’s causing what. “We don’t know which is the chicken and which is the egg,” said Dr. Acarli.
 

Headache triggers

Commenting for this news organization, Raquel Gil-Gouveia, MD, PhD, head of the neurology department, Hospital da Luz, Lisbon, Portugal, who co-chaired the session where the research was presented, said the information collected for the study was “extensive.”

Some results were expected, including the fact that patients with headaches were more anxious and depressed, said Dr. Gil-Gouveia.

“Anxiety and depression are frequent comorbidities of headache and can act as a triggering factor for headache attacks but can also be a consequence of intense or chronic pain,” she said.

She agreed the new results differ from those of studies carried out during the first pandemic lockdown, which showed an improvement in headache, but noted online learning was not fully implemented at that time, “so it was much like being on vacation.”

In addition to isolation, anxiety, and prolonged screen exposure, the lack of peer contact and fewer sports and leisure activities may also have contributed to worsening headaches during the COVID lockdown, but these were not explored in this study, said Dr. Gil-Gouveia.

The study was supported by the Global Migraine and Pain Society. The investigators and Dr. Gil-Gouveia report no relevant financial relationships.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

As the coronavirus continues to evolve, Omicron subvariants such as BA.4 and BA.5 are expected to lead to many COVID-19 cases in the coming months.

Researchers recently reported that the subvariants have mutated for better “immune escape,” or the ability to avoid antibodies from vaccination or previous infection.

“That has changed our view for what will happen this summer,” Ali Mokdad, PhD, an epidemiologist who has developed COVID-19 forecasts for the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, told The Boston Globe.

Until recently, Dr. Mokdad expected the United States to have a “very good summer” in terms of cases, hospitalizations, and deaths through September. The U.S. is reporting about 100,000 new cases per day, according to the data tracker by The New York Times, which has remained flat throughout June. Cases will likely decrease this summer, Dr. Mokdad said, though the decline will be slower and smaller than first thought.

As of June 18, BA.4 and BA.5 accounted for about 35% of cases in the United States, according to the latest CDC data, with BA.5 making up 23.5% and BA.4 making up 11.4%. The two subvariants will likely take over BA.2.12.1 as top subvariants in coming weeks.

“I expect that BA.5 will likely become the dominant virus in the United States this summer,” Dan Barouch, MD, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, told the Globe.

Dr. Barouch said the Omicron subvariants will likely create a summer of “substantial infections” but low rates of hospitalization and death. He published a recent study in the New England Journal of Medicine that found BA.4 and BA.5 are better at escaping antibodies than other coronavirus strains – about three times better than the Omicron variants BA.1 and BA.2 and 20 times better than the first coronavirus strain.

“What we’re seeing with each subsequent variant is iteratively higher levels of transmissibility and higher levels of antibody immune escape,” he said. “We’re seeing high levels of infection in populations that are highly vaccinated, as well as populations that have a high level of natural immunity to the prior variants.”

At the same time, current antibodies still appear to protect people against the worst outcomes, Dr. Barouch said.

“If people have vaccine immunity or natural immunity, then they have substantial protection against severe disease,” he said.

So far, researchers have found that Omicron subvariants tend to cause less severe disease than other variants, such as Delta. Dr. Mokdad estimated that 80% of Omicron infections don’t show symptoms.

He said there is a “remote possibility” of another wave during the summer, but he expects cases to rise significantly around the beginning of October, when the seasons change, and most people’s immunity will wane. Other things could play into the predictions this summer, he noted, such as coronavirus mutations and new variants.

“Anybody that models this more than a couple of weeks out is basically just using pixie dust,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told the newspaper.

“There is no pattern whatsoever developing from a seasonality standpoint. It’s all being driven by the variants,” he said. “We just have to be humble and acknowledge that we don’t know.”

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

As the coronavirus continues to evolve, Omicron subvariants such as BA.4 and BA.5 are expected to lead to many COVID-19 cases in the coming months.

Researchers recently reported that the subvariants have mutated for better “immune escape,” or the ability to avoid antibodies from vaccination or previous infection.

“That has changed our view for what will happen this summer,” Ali Mokdad, PhD, an epidemiologist who has developed COVID-19 forecasts for the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, told The Boston Globe.

Until recently, Dr. Mokdad expected the United States to have a “very good summer” in terms of cases, hospitalizations, and deaths through September. The U.S. is reporting about 100,000 new cases per day, according to the data tracker by The New York Times, which has remained flat throughout June. Cases will likely decrease this summer, Dr. Mokdad said, though the decline will be slower and smaller than first thought.

As of June 18, BA.4 and BA.5 accounted for about 35% of cases in the United States, according to the latest CDC data, with BA.5 making up 23.5% and BA.4 making up 11.4%. The two subvariants will likely take over BA.2.12.1 as top subvariants in coming weeks.

“I expect that BA.5 will likely become the dominant virus in the United States this summer,” Dan Barouch, MD, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, told the Globe.

Dr. Barouch said the Omicron subvariants will likely create a summer of “substantial infections” but low rates of hospitalization and death. He published a recent study in the New England Journal of Medicine that found BA.4 and BA.5 are better at escaping antibodies than other coronavirus strains – about three times better than the Omicron variants BA.1 and BA.2 and 20 times better than the first coronavirus strain.

“What we’re seeing with each subsequent variant is iteratively higher levels of transmissibility and higher levels of antibody immune escape,” he said. “We’re seeing high levels of infection in populations that are highly vaccinated, as well as populations that have a high level of natural immunity to the prior variants.”

At the same time, current antibodies still appear to protect people against the worst outcomes, Dr. Barouch said.

“If people have vaccine immunity or natural immunity, then they have substantial protection against severe disease,” he said.

So far, researchers have found that Omicron subvariants tend to cause less severe disease than other variants, such as Delta. Dr. Mokdad estimated that 80% of Omicron infections don’t show symptoms.

He said there is a “remote possibility” of another wave during the summer, but he expects cases to rise significantly around the beginning of October, when the seasons change, and most people’s immunity will wane. Other things could play into the predictions this summer, he noted, such as coronavirus mutations and new variants.

“Anybody that models this more than a couple of weeks out is basically just using pixie dust,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told the newspaper.

“There is no pattern whatsoever developing from a seasonality standpoint. It’s all being driven by the variants,” he said. “We just have to be humble and acknowledge that we don’t know.”

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

As the coronavirus continues to evolve, Omicron subvariants such as BA.4 and BA.5 are expected to lead to many COVID-19 cases in the coming months.

Researchers recently reported that the subvariants have mutated for better “immune escape,” or the ability to avoid antibodies from vaccination or previous infection.

“That has changed our view for what will happen this summer,” Ali Mokdad, PhD, an epidemiologist who has developed COVID-19 forecasts for the University of Washington’s Institute for Health Metrics and Evaluation in Seattle, told The Boston Globe.

Until recently, Dr. Mokdad expected the United States to have a “very good summer” in terms of cases, hospitalizations, and deaths through September. The U.S. is reporting about 100,000 new cases per day, according to the data tracker by The New York Times, which has remained flat throughout June. Cases will likely decrease this summer, Dr. Mokdad said, though the decline will be slower and smaller than first thought.

As of June 18, BA.4 and BA.5 accounted for about 35% of cases in the United States, according to the latest CDC data, with BA.5 making up 23.5% and BA.4 making up 11.4%. The two subvariants will likely take over BA.2.12.1 as top subvariants in coming weeks.

“I expect that BA.5 will likely become the dominant virus in the United States this summer,” Dan Barouch, MD, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, told the Globe.

Dr. Barouch said the Omicron subvariants will likely create a summer of “substantial infections” but low rates of hospitalization and death. He published a recent study in the New England Journal of Medicine that found BA.4 and BA.5 are better at escaping antibodies than other coronavirus strains – about three times better than the Omicron variants BA.1 and BA.2 and 20 times better than the first coronavirus strain.

“What we’re seeing with each subsequent variant is iteratively higher levels of transmissibility and higher levels of antibody immune escape,” he said. “We’re seeing high levels of infection in populations that are highly vaccinated, as well as populations that have a high level of natural immunity to the prior variants.”

At the same time, current antibodies still appear to protect people against the worst outcomes, Dr. Barouch said.

“If people have vaccine immunity or natural immunity, then they have substantial protection against severe disease,” he said.

So far, researchers have found that Omicron subvariants tend to cause less severe disease than other variants, such as Delta. Dr. Mokdad estimated that 80% of Omicron infections don’t show symptoms.

He said there is a “remote possibility” of another wave during the summer, but he expects cases to rise significantly around the beginning of October, when the seasons change, and most people’s immunity will wane. Other things could play into the predictions this summer, he noted, such as coronavirus mutations and new variants.

“Anybody that models this more than a couple of weeks out is basically just using pixie dust,” Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, told the newspaper.

“There is no pattern whatsoever developing from a seasonality standpoint. It’s all being driven by the variants,” he said. “We just have to be humble and acknowledge that we don’t know.”

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

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

[email protected]

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

[email protected]

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

[email protected]

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

[email protected]

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

[email protected]

The COVID-19 prevention effort in children enters its next phase as June draws to a close, while new pediatric cases continued on a downward trend and hospitalizations continued to rise.

The COVID-19 vaccines from Pfizer-BioNTech and Moderna were approved for use in children as young as 6 months, the Centers for Disease Control and Prevention announced on June 18.

“We know millions of parents and caregivers are eager to get their young children vaccinated. ... I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations,” CDC Director Rochelle P. Walensky, MD, MPH, said in a written statement.

There are, however, indications that many parents are not that eager. A survey conducted in April by the Kaiser Family Foundation showed that only about 18% of parents were eager to get their children under age 5 years vaccinated right away and 27% said they would “definitely not” get their children vaccinated. Another 11% said “they will only do so if they are required,” Kaiser noted.

The vaccination experience with children aged 5-11 years seems to agree with those numbers. As of June 16, more than 7 months after the vaccine became available, just over 36% had received at least one dose and about 30% were fully vaccinated, CDC data show.

There are, according to the American Academy of Pediatrics, still five states where less than 20% of eligible 5- to 11-year-olds have received an initial vaccination. Among children aged 12-17, uptake has been much higher: 70% have received at least one dose and 60% are fully vaccinated, the CDC said.

Trends for new cases, hospitalizations diverging

COVID incidence in children, meanwhile, dropped for the second time in 3 weeks. There were 83,000 new cases reported during June 10-16, a decline of 4.8% from the previous week, according to the AAP and the Children’s Hospital Association.

New cases had risen by a very slight 0.31% during the week of June 3-9 after dropping 22% the week before (May 27 to June 2). Total cases in children have surpassed 13.6 million, which represents 18.8% of cases in all ages since the start of the pandemic, the AAP and CHA said in their weekly COVID report.

New admissions of children with confirmed COVID-19, however, have continued to climb since early to mid April. On June 16, the rate for children aged 0-17 years was up to 0.31 per 100,000, compared with the 0.13 per 100,000 recorded as late as April 11, the CDC said on its COVID Data Tracker.

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NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

NATIONAL HARBOR, MD. – The latest updates on COVID-19 vaccination response among patients with multiple sclerosis (MS) who are treated with disease-modifying therapy (DMT) show that, if patients do contract the virus, cases are mild and serious infections are rare.

However, vaccine antibody response remains lower with anti-CD20 therapies.

One of several late-breaking studies on these issues that were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers included more than 100 patients with MS who were treated with a variety of DMTs.

Results showed that the rate of antibody response was just 55% among those treated with anti-CD20 therapies versus 83% for those treated with other DMTs, including sphingosine-1-phosphate receptor modulators (S1Ps).

Consistent with what has been observed in other studies, “vaccine antibody responses were slightly lower in B cell–depleted patients than with other therapies,” senior author Rahul Dave, MD, director of the INOVA MS and Neuroimmunology Center, Inova Neurosciences Institute, the University of Virginia, Fairfax, said in an interview.
 

Vaccine response

The investigators sought to assess detailed vaccine responses in 134 patients with MS. Serum COVID antibody measures were conducted approximately 3 weeks to 4 months after vaccination – and mostly after the initial vaccination.

The antibody response rate was significantly lower with anti-CD20 treatments (55%) than with all other DMTs examined (83%), including S1Ps, immunomodulators, immunosuppressive drugs, interferon B, anti-CD52, and natalizumab (P < .01).

The highest prevalence of antibody response was observed among those taking immunomodulators; responses occurred among 91% of patients taking teriflunomide and among 93% of those taking fumarates.

Among those treated with anti-CD20 therapy, antibody responses correlated with higher baseline immunoglobulin levels (P = .01) and shorter durations of therapy.

“We found that longer total duration of therapy and lower immunoglobulin levels tended to correlate with decreases in immune responses,” said Dr. Dave.

“Interestingly, the timing between vaccination versus administration of [anti-CD20 drug] ocrelizumab did not seem to be impactful with regards to antibody responses,” Dr. Dave noted. He added that this is contrary to some past studies that showed benefits if the vaccination could be completed prior to starting ocrelizumab.

Sixteen participants tested polymerase chain reaction positive for COVID during the previous 12 months. Although most infections were described as mild and self-limited, four of the patients received outpatient monoclonal antibody therapy, and one required hospitalization because of COVID.

“I think it is notable and reassuring that, overall, our patients had mild courses. This is consistent with the vaccines ‘working,’ and is true even in patients on high-efficacy immunosuppressants that partially abrogate antibody responses,” Dr. Dave said.

He added that he reassures patients who need high-efficacy therapies that “they should use them.”

That being said, as in the general population, even vaccinated patients can get COVID. “You can be sick and feel terrible, but in general, hospitalization numbers are way down compared to 2 years ago. We are seeing the same trends in MS patients, including the B cell–depleted patients,” he said.

“To get at the question whether B cell–depleted patients behave exactly the same as the general population, or even [with] other DMTs, we will need large, multicenter, prospective datasets,” said Dr. Dave.
 

Favorable findings

Two other late-breaking posters at the meeting provided updates regarding antibody responses among patients receiving S1Ps. There has been concern that S1Ps may blunt antibody responses to COVID vaccinations.

The concern is in regard to their unique mechanisms of sequestering circulating lymphocytes, particularly the older, nonselective S1P receptor modulator fingolimod, said the author of one of the studies, Daniel Kantor, MD, president emeritus of the Florida Society of Neurology and founding president of the Medical Partnership 4 MS+.

“It appears the issues with fingolimod might relate to the level of white blood cell sequestration, [which is] greater in fingolimod than the newer S1P receptor modulators, and/or the result of S1P4 receptor modulation, which is not seen with the newer, selective medications,” Dr. Kantor said in an interview.

In a prospective observational trial of patients with relapsing MS, among 30 participants who were treated with ozanimod, the mean increase in IgG antibody titer 4 weeks after either of the two available mRNA vaccines was 232.73 AU/mL versus a mean increase of 526.59 AU/mL among 30 non–ozanimod/DMT-treated patients.

To date, only three patients in the study were taking ocrelizumab; for those patients, the mean increase in IgG titers was 0.633.

Despite the lower antibody titers in the ozanimod-treated patients, which Dr. Kantor noted are generally regarded as protective, all but one of the patients had positive results on T-Detect, which was indicative of vaccine protection.

“In this study, [relapsing] MS patients treated with ozanimod had an antibody and T-cell response to the mRNA COVID-19 vaccines,” he reported. “This trial is ongoing, with 48 weeks of follow-up expected in December 2022.”
 

Ponesimod results

In the other S1P modulator-related late-breaking study, Janssen Research and Development reported on antibody responses of patients who were treated with the S1P drug ponesimod in the phase 2 AC-058B202 study.

The median exposure to ponesimod at time of vaccination was 10.7 years (range, 9.8-11.8 years). There were 134 patients in the study. Of those, both prevaccination and postvaccination blood samples from 49 patients were tested for spike antibody concentrations.

Among those participants, 40 (81.6%) met the definition of response to the COVID-19 vaccination, defined as seroconversion in the case of negative prevaccination antibody testing or a fourfold antibody concentration increase in the case of a positive prevaccination antibody result.

Of the 38 antibody-negative participants, 33 (86.8%) achieved seroconversion post vaccination.

A total of 20 participants reported having had prevaccine COVID, while 17 had postvaccination COVID.

None of the cases were serious, severe, or fatal, and none led to permanent treatment discontinuation.

“In patients with RMS on ponesimod, the majority (> 80%) appear to develop a measurable SARS-CoV-2 humoral response after COVID-19 vaccination,” the authors, led by Janice Wong, of Janssen Research and Development, wrote.

“Further investigations on the efficacy and safety of COVID-19 vaccination in MS patients on ponesimod are warranted,” they added.

In a final study from Genentech, of 4848 patients with MS who were fully vaccinated during the Delta and Omicron waves, 1.3% had a COVID-related hospitalization. In addition, rate of severe SARS-CoV-2 infections was very low (0.6%); there were fewer than 10 infections in each subgroup of DMTs. These patients included 585 (17%) who were treated with ocrelizumab, 238 (7%) who were treated with S1P receptor modulators, 33 (1%) who were treated with interferons, 1,004 (29%) who were treated with other DMTs, and 1,574 (46%) for whom no DMTs were recorded.

“We can conclude from this study that the characteristics of people with MS with more severe COVID-19 outcomes resemble those observed in the general population,” such as in those who are older or have higher rates of comorbidities, Preeti Bajaj, team lead of HEOR, Neuroscience, at Genentech, said in an interview. “We believe [ocrelizumab] treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit-risk assessment specific to the individual patient.”
 

Concerns remain

In a comment, Bruce A. C. Cree, MD, PhD, professor of clinical neurology and clinical research director at the Weill Institute for Neurosciences, University of California, San Francisco, described the overall data on vaccine efficacy on anti-CD20s as “discouraging” and said he is adjusting his own recommendations for these patients.

“Repeated vaccinations do not seem to stimulate humoral responses in B cell–depleted patients,” said Dr. Cree, who was not involved with the research.

“In my personal practice, I have been suspending dosing in my patients to allow for B-cell reconstitution to occur followed by revaccination,” he added.

Regarding the S1P drugs, he noted that, aside from fingolimod, “the antibody response frequency seems to be better than initial reports. However, the index values are low and may not be protective.”

Overall, the take-home message for patients with MS who are taking DMTs should be, “all patients treated with S1P modulators or anti-C20 antibodies should be vaccinated and boosted,” Dr. Cree said.

“In some cases, temporary interruption of treatment might be useful to help develop robust responses to vaccinations,” he added.

Dr. Dave reported no financial relationships regarding the poster but is a paid speaker/consultant for Novartis, Bristol-Myers Squibb, EMD Serono, Biogen, Alexion, Genentech, Horizon, and Sanofi for their MS & NMO therapies. Dr. Kantor’s research was supported by a grant from BMS; he is a consultant for Biogen, BMS, and Janssen. Dr. Cree reported that he is an unpaid consultant for BMS, the manufacturer of ozanimod.

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

A rapid, saliva-based test for COVID-19 could enable testing, diagnosis, and prescribing to take place in a single office visit by immediately confirming whether a patient has the infection and needs to be treated, researchers say. The test has sparked commercial interest and earned additional funding from the Canadian government.

The test uses a DNA aptamer – a short, synthetic oligonucleotide that binds to a specific molecular target – that shows high affinity for the SARS-CoV-2 spike protein and its variants. The approach “can be rapidly adapted to different threats,” as well, Leyla Soleymani, PhD, an associate professor of engineering physics at McMaster University, Hamilton, Ontario, Canada, told this news organization. Her team invented the approach.
 

Adaptable to other pathogens

Current gold-standard COVID-19 tests are based on reverse transcription-polymerase chain reaction (RT-PCR), which are sensitive but costly, complicated, and require waiting at least a couple of days for results, according to Dr. Soleymani and colleagues. Rapid nucleic acid and antigen tests have only “moderate” sensitivity and specificity, particularly when viral loads are low. None have been shown to work well with saliva samples.

By contrast, the new test “uses a reader and test cartridges, similar to the glucose reader,” said Dr. Soleymani, who is also Canada Research chair in Miniaturized Biomedical Devices. A small sample of saliva is added to a chemical reagent and inserted into the reader, which is attached to a smartphone. Once commercialized, the point-of-care test is expected to be performed quickly in a physician’s office or in a clinic.

“The same reader can be applied to a variety of infectious diseases or infection panels by developing new cartridges,” Dr. Soleymani explained. “Noroviruses and bacteria such as C. difficile are on our list” to examine next.What’s more, she added, “this test is ideally positioned for settings where access to centralized labs is not possible, such as less developed countries.”

The team’s recent studies seem to support the promise. A study published last year in the international edition of Angewandte Chemie documents the development of the test, which at that point could detect wild-type SARS-CoV-2 and its Alpha and Delta variants in unprocessed saliva samples in 10 minutes with 80.5% sensitivity and 100% specificity.

This study was followed in January 2022 by a paper in Chemistry showing that the device also detected Alpha, Gamma, Epsilon, Kappa, and Omicron variants, demonstrating its potential for recognizing rapidly evolving targets such as those found in SARS-CoV-2.

In another demonstration of its versatility, the technology was recently adapted and successfully detected animal viruses from saliva samples.
 

Commercial and government funding

The findings prompted Zentek, an intellectual property development and commercialization company in Guelph, Ont., to license the technology, with plans to invest more than $1 million in the next 5 years to scale up production of the test components and adapt the technology for other forms of infection.

Furthermore, the collaborative efforts required to develop the test and move it forward gained funding from Canada’s Natural Sciences and Engineering Research Council, which is investing nearly $1.5 million in the form of two grants: $1 million to further streamline the technology development in preparation for the next pandemic and $488,440 (including $140,000 from Zentek) to get the current test to market as quickly as possible.

Meanwhile, Dr. Soleymani is urging clinicians “to be open to nontraditional diagnostic approaches even if the traditional tests do the job. Such tests are more rapid and can be used to enable personalized medicine. Our success relies on collaboration and support from clinicians.”
 

Further validation needed

Daniel Kuritzkes, MD, chief of infectious diseases at Brigham and Women’s Hospital and the Harriet Ryan Albee Professor of Medicine at Harvard Medical School, Boston, commented on the study in response to a request from this news organization.

While “it’s always good to have more testing options available,” he said, “we don’t yet have very much information about performance characteristics of the test – that is, its sensitivity and specificity. I’d like to see the performance characteristics of this test compared to PCR tests and to the current rapid antigen tests using a large number of patient samples with currently circulating variants, and tests over time to see how soon tests become positive after symptom onset and for how long they remain positive.”

“Further validation studies and emergency use authorization or approval by regulatory authorities are needed before we will see this test implemented in the field,” Dr. Kuritzkes concluded.

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

A rapid, saliva-based test for COVID-19 could enable testing, diagnosis, and prescribing to take place in a single office visit by immediately confirming whether a patient has the infection and needs to be treated, researchers say. The test has sparked commercial interest and earned additional funding from the Canadian government.

The test uses a DNA aptamer – a short, synthetic oligonucleotide that binds to a specific molecular target – that shows high affinity for the SARS-CoV-2 spike protein and its variants. The approach “can be rapidly adapted to different threats,” as well, Leyla Soleymani, PhD, an associate professor of engineering physics at McMaster University, Hamilton, Ontario, Canada, told this news organization. Her team invented the approach.
 

Adaptable to other pathogens

Current gold-standard COVID-19 tests are based on reverse transcription-polymerase chain reaction (RT-PCR), which are sensitive but costly, complicated, and require waiting at least a couple of days for results, according to Dr. Soleymani and colleagues. Rapid nucleic acid and antigen tests have only “moderate” sensitivity and specificity, particularly when viral loads are low. None have been shown to work well with saliva samples.

By contrast, the new test “uses a reader and test cartridges, similar to the glucose reader,” said Dr. Soleymani, who is also Canada Research chair in Miniaturized Biomedical Devices. A small sample of saliva is added to a chemical reagent and inserted into the reader, which is attached to a smartphone. Once commercialized, the point-of-care test is expected to be performed quickly in a physician’s office or in a clinic.

“The same reader can be applied to a variety of infectious diseases or infection panels by developing new cartridges,” Dr. Soleymani explained. “Noroviruses and bacteria such as C. difficile are on our list” to examine next.What’s more, she added, “this test is ideally positioned for settings where access to centralized labs is not possible, such as less developed countries.”

The team’s recent studies seem to support the promise. A study published last year in the international edition of Angewandte Chemie documents the development of the test, which at that point could detect wild-type SARS-CoV-2 and its Alpha and Delta variants in unprocessed saliva samples in 10 minutes with 80.5% sensitivity and 100% specificity.

This study was followed in January 2022 by a paper in Chemistry showing that the device also detected Alpha, Gamma, Epsilon, Kappa, and Omicron variants, demonstrating its potential for recognizing rapidly evolving targets such as those found in SARS-CoV-2.

In another demonstration of its versatility, the technology was recently adapted and successfully detected animal viruses from saliva samples.
 

Commercial and government funding

The findings prompted Zentek, an intellectual property development and commercialization company in Guelph, Ont., to license the technology, with plans to invest more than $1 million in the next 5 years to scale up production of the test components and adapt the technology for other forms of infection.

Furthermore, the collaborative efforts required to develop the test and move it forward gained funding from Canada’s Natural Sciences and Engineering Research Council, which is investing nearly $1.5 million in the form of two grants: $1 million to further streamline the technology development in preparation for the next pandemic and $488,440 (including $140,000 from Zentek) to get the current test to market as quickly as possible.

Meanwhile, Dr. Soleymani is urging clinicians “to be open to nontraditional diagnostic approaches even if the traditional tests do the job. Such tests are more rapid and can be used to enable personalized medicine. Our success relies on collaboration and support from clinicians.”
 

Further validation needed

Daniel Kuritzkes, MD, chief of infectious diseases at Brigham and Women’s Hospital and the Harriet Ryan Albee Professor of Medicine at Harvard Medical School, Boston, commented on the study in response to a request from this news organization.

While “it’s always good to have more testing options available,” he said, “we don’t yet have very much information about performance characteristics of the test – that is, its sensitivity and specificity. I’d like to see the performance characteristics of this test compared to PCR tests and to the current rapid antigen tests using a large number of patient samples with currently circulating variants, and tests over time to see how soon tests become positive after symptom onset and for how long they remain positive.”

“Further validation studies and emergency use authorization or approval by regulatory authorities are needed before we will see this test implemented in the field,” Dr. Kuritzkes concluded.

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

A rapid, saliva-based test for COVID-19 could enable testing, diagnosis, and prescribing to take place in a single office visit by immediately confirming whether a patient has the infection and needs to be treated, researchers say. The test has sparked commercial interest and earned additional funding from the Canadian government.

The test uses a DNA aptamer – a short, synthetic oligonucleotide that binds to a specific molecular target – that shows high affinity for the SARS-CoV-2 spike protein and its variants. The approach “can be rapidly adapted to different threats,” as well, Leyla Soleymani, PhD, an associate professor of engineering physics at McMaster University, Hamilton, Ontario, Canada, told this news organization. Her team invented the approach.
 

Adaptable to other pathogens

Current gold-standard COVID-19 tests are based on reverse transcription-polymerase chain reaction (RT-PCR), which are sensitive but costly, complicated, and require waiting at least a couple of days for results, according to Dr. Soleymani and colleagues. Rapid nucleic acid and antigen tests have only “moderate” sensitivity and specificity, particularly when viral loads are low. None have been shown to work well with saliva samples.

By contrast, the new test “uses a reader and test cartridges, similar to the glucose reader,” said Dr. Soleymani, who is also Canada Research chair in Miniaturized Biomedical Devices. A small sample of saliva is added to a chemical reagent and inserted into the reader, which is attached to a smartphone. Once commercialized, the point-of-care test is expected to be performed quickly in a physician’s office or in a clinic.

“The same reader can be applied to a variety of infectious diseases or infection panels by developing new cartridges,” Dr. Soleymani explained. “Noroviruses and bacteria such as C. difficile are on our list” to examine next.What’s more, she added, “this test is ideally positioned for settings where access to centralized labs is not possible, such as less developed countries.”

The team’s recent studies seem to support the promise. A study published last year in the international edition of Angewandte Chemie documents the development of the test, which at that point could detect wild-type SARS-CoV-2 and its Alpha and Delta variants in unprocessed saliva samples in 10 minutes with 80.5% sensitivity and 100% specificity.

This study was followed in January 2022 by a paper in Chemistry showing that the device also detected Alpha, Gamma, Epsilon, Kappa, and Omicron variants, demonstrating its potential for recognizing rapidly evolving targets such as those found in SARS-CoV-2.

In another demonstration of its versatility, the technology was recently adapted and successfully detected animal viruses from saliva samples.
 

Commercial and government funding

The findings prompted Zentek, an intellectual property development and commercialization company in Guelph, Ont., to license the technology, with plans to invest more than $1 million in the next 5 years to scale up production of the test components and adapt the technology for other forms of infection.

Furthermore, the collaborative efforts required to develop the test and move it forward gained funding from Canada’s Natural Sciences and Engineering Research Council, which is investing nearly $1.5 million in the form of two grants: $1 million to further streamline the technology development in preparation for the next pandemic and $488,440 (including $140,000 from Zentek) to get the current test to market as quickly as possible.

Meanwhile, Dr. Soleymani is urging clinicians “to be open to nontraditional diagnostic approaches even if the traditional tests do the job. Such tests are more rapid and can be used to enable personalized medicine. Our success relies on collaboration and support from clinicians.”
 

Further validation needed

Daniel Kuritzkes, MD, chief of infectious diseases at Brigham and Women’s Hospital and the Harriet Ryan Albee Professor of Medicine at Harvard Medical School, Boston, commented on the study in response to a request from this news organization.

While “it’s always good to have more testing options available,” he said, “we don’t yet have very much information about performance characteristics of the test – that is, its sensitivity and specificity. I’d like to see the performance characteristics of this test compared to PCR tests and to the current rapid antigen tests using a large number of patient samples with currently circulating variants, and tests over time to see how soon tests become positive after symptom onset and for how long they remain positive.”

“Further validation studies and emergency use authorization or approval by regulatory authorities are needed before we will see this test implemented in the field,” Dr. Kuritzkes concluded.

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