COVID-19 Updates

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

• Over age 65
• Ages 18 to 64 who are at higher risk for severe COVID
• Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

• Over age 65
• Ages 18 to 64 who are at higher risk for severe COVID
• Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

• Over age 65
• Ages 18 to 64 who are at higher risk for severe COVID
• Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

Most vaccines are given with hypodermic needle injections. But shots aren’t necessarily the most efficient or effective way to deliver a vaccine. Scientists have been experimenting with microneedle patches to painlessly deliver a vaccine into the outermost layer of the skin with dozens of extremely tiny needles coated in the vaccine solution.

Now, researchers have found a three-dimensional printing method that lets them customize microneedle shapes in the patches for different pathogens, such as flu, measles, hepatitis, or COVID-19. In tests using mice, the patches led to stronger and longer-lasting immune responses than traditional shots under the skin. The research team described their findings in the Proceedings of the National Academy of Sciences.
 

Tiny needles, big advantages

Previous research has shown delivering vaccines into the skin can cause a stronger immune response because the skin has a high concentration of immune cells. But shots can be painful and require skilled medical providers.

Microneedles painlessly deliver the vaccine into the skin without the need for a trained clinician. In fact, a person can even give the vaccine to themselves.

The needles – made of metal, silicon, or plastic – are so tiny that they puncture only the tough outermost layer of skin. The prospect of a painless vaccination without a hypodermic needle may ease anxiety in people who fear needles.

Scientists also can store dried patches after coating them with the vaccine solution, so there’s no preparation needed before giving the vaccine and the patches may not even require cold storage. This latest study suggests that the patches generate a stronger immune response than standard shots, allowing for a smaller dose than traditional vaccine delivery methods and possibly fewer side effects.
 

Breaking the mold

Past methods of making microneedle patches often used molds, but that approach limited the ability to customize patches for different diseases. Repeatedly using same mold also can blunt the tiny needles.

For the three-dimensional–printed patches, Cassie Caudill at the University of North Carolina at Chapel Hill and colleagues used a printing technique that allows greater control over and consistency in the shape of the microneedles. The investigators printed two shapes: a slender pyramid microneedle that is similar to previous versions, and one with serrated grooves that resembles a pine tree.

The increased surface area from the grooves let researchers add 36% more of the ingredient that causes an immune response, compared with using only the pyramid shape, yet still less than a conventional shot. At only 1 cm by 1 cm, each patch contains 100 microneedles that are just over 1 mm long. The researchers found that in mice the patch drew a stronger immune response than a conventional shot, despite carrying a much smaller dose of vaccine ingredient.

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

The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.

The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.

“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”

The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”

“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.

Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
 

Uncertain utility

The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.

This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.

They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.

Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.

The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.

Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.

Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).

The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.

D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).

A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.

The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.

The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
 

D-dimer in VTE may not extrapolate to COVID-19

“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.

“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.

“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.

Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.

“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.

“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.

“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”

Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.

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

The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.

The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.

“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”

The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”

“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.

Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
 

Uncertain utility

The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.

This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.

They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.

Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.

The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.

Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.

Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).

The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.

D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).

A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.

The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.

The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
 

D-dimer in VTE may not extrapolate to COVID-19

“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.

“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.

“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.

Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.

“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.

“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.

“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”

Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.

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

The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.

The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.

“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”

The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”

“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.

Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
 

Uncertain utility

The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.

This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.

They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.

Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.

The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.

Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.

Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).

The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.

D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).

A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.

The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.

The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
 

D-dimer in VTE may not extrapolate to COVID-19

“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.

“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.

“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.

Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.

“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.

“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.

“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”

Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.

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

New data on COVID vaccination in patients with multiple sclerosis (MS) has shown a reduced humoral response in patients treated with the anti-CD20 antibodies ocrelizumab or rituximab, but not in those receiving the similar product, ofatumumab.

The results also show a reduced response to COVID vaccination in some patients on fingolimod.

The data come from a new series of vaccinated patients with MS from Madrid, which was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Presenting the data, Celia Oreja-Guevara, MD, Hospital Clínico San Carlos, Madrid, concluded that “currently approved COVID-19 vaccines appear safe in MS patients and are effective in most patients. However, vaccine strategy in patients treated with anti-CD20 and S1P inhibitors [such as fingolimod] need further study.”

“We showed that patients on ocrelizumab or rituximab had a very low or no antibody response to COVID vaccination,” she added. “However, some previous studies have shown some T-cell response to vaccination in these patients, and we are looking at that now.”
 

Assessing postvaccination antibody response

For the current study, the researchers analyzed the antibody response to COVID-19 vaccination at week 3, week 6, and month 3 after the first dose in 165 patients with MS and 200 healthy controls.

Of the patients with MS, 120 received both doses of mRNA vaccine and 42 received the AstraZeneca vaccine. The mean age of the MS patients was 45 years and 46 years in the healthy controls.

Adverse events were similar in the two groups, and no increase in relapse activity was seen in the patients with MS.

Mean antibody titers were slightly lower in the patients with MS versus the healthy controls. At 3 weeks, mean titers were 7,910 AU/mL in the patients with MS and 9,397 in the healthy controls. At 6 weeks, mean levels were 16,347 AU/mL in the patients with MS and 18,120 in the healthy controls.

Patients with MS treated with interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, and natalizumab who received mRNA vaccines developed a similar postvaccination humoral response as the healthy controls at each of 3, 6, and 12 weeks after the first dose.

Patients with MS receiving the AstraZeneca vaccine mounted a lower humoral response than those receiving the mRNA vaccine, but this same effect was also seen in the healthy controls.

However, patients on the anti-CD20 drugs ocrelizumab or rituximab showed a lower humoral response to COVID vaccination. Only 3 of 20 patients who had been treated with ocrelizumab developed antibodies, but these patients had longer washout periods (at least 6 months) between receiving ocrelizumab and the COVID vaccine. All six patients treated with rituximab had no antibody response to the COVID vaccination.

Dr. Oreja-Guevara suggested that ocrelizumab-treated patients may have a worse outcome after COVID-19 infection. “In the first wave of infection in Madrid, we recorded five patients on ocrelizumab with COVID-19, four of whom were hospitalized,” she noted.

“In patients on ocrelizumab we need to try and have a long interval between giving this drug and giving the COVID vaccine. The longer the washout period, the more antibodies are seen,” she said.

She noted that two patients in the study received the COVID vaccine 1 year after ocrelizumab administration and had a normal humoral response, similar to the healthy controls.

The new anti-CD20 drug, ofatumumab, did not seem to affect the COVID vaccine antibody response as much as ocrelizumab or rituximab. In the current study, four of five patients treated with ofatumumab had an antibody response.

Dr. Oreja-Guevara suggested that this was probably because the depletion of B cells is not so strong with ofatumumab. “This drug is dosed every 4 weeks and it doesn’t deplete all the B cells and they are replaced quite quickly.”

Fingolimod is another MS drug that seems to affect the antibody response to COVID-19 vaccination.

Dr. Oreja-Guevara described the response to COVID vaccination in patients on fingolimod as “very variable.” Of 16 patients treated with fingolimod, 4 failed to develop a humoral response, 7 had a low antibody response, and 5 had a similar response to that seen in the healthy controls (three of these patients had also had a previous COVID-19 infection). The response to vaccination in fingolimod-treated patients did not appear to be related to lymphopenia.
 

Cellular response also impaired with fingolimod

These data are consistent with those from another cohort from Israel reported previously.

In that study, which was published earlier in 2021, a team led by Anat Achiron, MD, Sheba Medical Center, Tel Aviv, analyzed humoral immunity in 125 patients with MS 1 month after the second dose of the Pfizer COVID vaccine. A group of healthy people similarly vaccinated served as control.

Results showed that protective humoral immunity occurred in 97.9% of the control group after vaccination, compared with 100% in untreated patients and 100% in patients treated with cladribine but in just 22.7% of those treated with ocrelizumab and only 3.8% of those taking fingolimod.

For ocrelizumab-treated patients, the failure to mount appropriate IgG immune response was regardless of the absolute lymphocyte counts that were in the normal range or to the time interval from the last ocrelizumab treatment dose that ranged from 3.1 to 8.9 months, “suggesting the need to postpone the next dosing to enable an effective postvaccination humoral response,” the authors said.

They noted that the majority of the fingolimod-treated patients in the study had a low lymphocyte count (<1,000 cells/mm³), which may be the cause for failing to mount an immune response. But even in the small group of fingolimod-treated MS patients with an absolute lymphocyte count above 1,000 cells/mm³, no humoral response was detected.

At the ECTRIMS meeting, Dr. Achiron presented further results from this study on memory B-cell and T-cell responses to the COVID vaccine in these patients.

The results showed that COVID-specific B- and T-cell responses were only present in about half of healthy subjects, untreated patients with MS, and those treated with cladribine.

While the B-cell response was almost completely impaired in the ocrelizumab-treated patients, the T-cell response was present to the same extent as in the control group. But fingolimod patients showed no B- or T-cell responses.

Dr. Achiron concluded that patients on ocrelizumab should wait at least 9 months following the last dose before receiving COVID vaccination, and that patients taking fingolimod should consider a switch to a different medication.

But she pointed out that, despite the lack of humoral cellular responses in the fingolimod group, in this study there does not seem to have been an increase in COVID infection in patients taking fingolimod in a large registry study.

“This leads us to the idea that maybe lymphopenia is not the only story, and maybe innate immunity is playing a role. We still don’t really know the answer for that.”

Dr. Achiron said she was also surprised to see that even untreated and healthy subjects did not develop complete B-cell and T-cell responses after double COVID vaccination. And similar results have been seen in patients who have recovered from natural COVID infection, where the B-cell response is “not 100%,” she added.

“This points to the suggestion that everyone might need a third vaccination, MS patients or not,” she concluded.

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

New data on COVID vaccination in patients with multiple sclerosis (MS) has shown a reduced humoral response in patients treated with the anti-CD20 antibodies ocrelizumab or rituximab, but not in those receiving the similar product, ofatumumab.

The results also show a reduced response to COVID vaccination in some patients on fingolimod.

The data come from a new series of vaccinated patients with MS from Madrid, which was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Presenting the data, Celia Oreja-Guevara, MD, Hospital Clínico San Carlos, Madrid, concluded that “currently approved COVID-19 vaccines appear safe in MS patients and are effective in most patients. However, vaccine strategy in patients treated with anti-CD20 and S1P inhibitors [such as fingolimod] need further study.”

“We showed that patients on ocrelizumab or rituximab had a very low or no antibody response to COVID vaccination,” she added. “However, some previous studies have shown some T-cell response to vaccination in these patients, and we are looking at that now.”
 

Assessing postvaccination antibody response

For the current study, the researchers analyzed the antibody response to COVID-19 vaccination at week 3, week 6, and month 3 after the first dose in 165 patients with MS and 200 healthy controls.

Of the patients with MS, 120 received both doses of mRNA vaccine and 42 received the AstraZeneca vaccine. The mean age of the MS patients was 45 years and 46 years in the healthy controls.

Adverse events were similar in the two groups, and no increase in relapse activity was seen in the patients with MS.

Mean antibody titers were slightly lower in the patients with MS versus the healthy controls. At 3 weeks, mean titers were 7,910 AU/mL in the patients with MS and 9,397 in the healthy controls. At 6 weeks, mean levels were 16,347 AU/mL in the patients with MS and 18,120 in the healthy controls.

Patients with MS treated with interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, and natalizumab who received mRNA vaccines developed a similar postvaccination humoral response as the healthy controls at each of 3, 6, and 12 weeks after the first dose.

Patients with MS receiving the AstraZeneca vaccine mounted a lower humoral response than those receiving the mRNA vaccine, but this same effect was also seen in the healthy controls.

However, patients on the anti-CD20 drugs ocrelizumab or rituximab showed a lower humoral response to COVID vaccination. Only 3 of 20 patients who had been treated with ocrelizumab developed antibodies, but these patients had longer washout periods (at least 6 months) between receiving ocrelizumab and the COVID vaccine. All six patients treated with rituximab had no antibody response to the COVID vaccination.

Dr. Oreja-Guevara suggested that ocrelizumab-treated patients may have a worse outcome after COVID-19 infection. “In the first wave of infection in Madrid, we recorded five patients on ocrelizumab with COVID-19, four of whom were hospitalized,” she noted.

“In patients on ocrelizumab we need to try and have a long interval between giving this drug and giving the COVID vaccine. The longer the washout period, the more antibodies are seen,” she said.

She noted that two patients in the study received the COVID vaccine 1 year after ocrelizumab administration and had a normal humoral response, similar to the healthy controls.

The new anti-CD20 drug, ofatumumab, did not seem to affect the COVID vaccine antibody response as much as ocrelizumab or rituximab. In the current study, four of five patients treated with ofatumumab had an antibody response.

Dr. Oreja-Guevara suggested that this was probably because the depletion of B cells is not so strong with ofatumumab. “This drug is dosed every 4 weeks and it doesn’t deplete all the B cells and they are replaced quite quickly.”

Fingolimod is another MS drug that seems to affect the antibody response to COVID-19 vaccination.

Dr. Oreja-Guevara described the response to COVID vaccination in patients on fingolimod as “very variable.” Of 16 patients treated with fingolimod, 4 failed to develop a humoral response, 7 had a low antibody response, and 5 had a similar response to that seen in the healthy controls (three of these patients had also had a previous COVID-19 infection). The response to vaccination in fingolimod-treated patients did not appear to be related to lymphopenia.
 

Cellular response also impaired with fingolimod

These data are consistent with those from another cohort from Israel reported previously.

In that study, which was published earlier in 2021, a team led by Anat Achiron, MD, Sheba Medical Center, Tel Aviv, analyzed humoral immunity in 125 patients with MS 1 month after the second dose of the Pfizer COVID vaccine. A group of healthy people similarly vaccinated served as control.

Results showed that protective humoral immunity occurred in 97.9% of the control group after vaccination, compared with 100% in untreated patients and 100% in patients treated with cladribine but in just 22.7% of those treated with ocrelizumab and only 3.8% of those taking fingolimod.

For ocrelizumab-treated patients, the failure to mount appropriate IgG immune response was regardless of the absolute lymphocyte counts that were in the normal range or to the time interval from the last ocrelizumab treatment dose that ranged from 3.1 to 8.9 months, “suggesting the need to postpone the next dosing to enable an effective postvaccination humoral response,” the authors said.

They noted that the majority of the fingolimod-treated patients in the study had a low lymphocyte count (<1,000 cells/mm³), which may be the cause for failing to mount an immune response. But even in the small group of fingolimod-treated MS patients with an absolute lymphocyte count above 1,000 cells/mm³, no humoral response was detected.

At the ECTRIMS meeting, Dr. Achiron presented further results from this study on memory B-cell and T-cell responses to the COVID vaccine in these patients.

The results showed that COVID-specific B- and T-cell responses were only present in about half of healthy subjects, untreated patients with MS, and those treated with cladribine.

While the B-cell response was almost completely impaired in the ocrelizumab-treated patients, the T-cell response was present to the same extent as in the control group. But fingolimod patients showed no B- or T-cell responses.

Dr. Achiron concluded that patients on ocrelizumab should wait at least 9 months following the last dose before receiving COVID vaccination, and that patients taking fingolimod should consider a switch to a different medication.

But she pointed out that, despite the lack of humoral cellular responses in the fingolimod group, in this study there does not seem to have been an increase in COVID infection in patients taking fingolimod in a large registry study.

“This leads us to the idea that maybe lymphopenia is not the only story, and maybe innate immunity is playing a role. We still don’t really know the answer for that.”

Dr. Achiron said she was also surprised to see that even untreated and healthy subjects did not develop complete B-cell and T-cell responses after double COVID vaccination. And similar results have been seen in patients who have recovered from natural COVID infection, where the B-cell response is “not 100%,” she added.

“This points to the suggestion that everyone might need a third vaccination, MS patients or not,” she concluded.

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

New data on COVID vaccination in patients with multiple sclerosis (MS) has shown a reduced humoral response in patients treated with the anti-CD20 antibodies ocrelizumab or rituximab, but not in those receiving the similar product, ofatumumab.

The results also show a reduced response to COVID vaccination in some patients on fingolimod.

The data come from a new series of vaccinated patients with MS from Madrid, which was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Presenting the data, Celia Oreja-Guevara, MD, Hospital Clínico San Carlos, Madrid, concluded that “currently approved COVID-19 vaccines appear safe in MS patients and are effective in most patients. However, vaccine strategy in patients treated with anti-CD20 and S1P inhibitors [such as fingolimod] need further study.”

“We showed that patients on ocrelizumab or rituximab had a very low or no antibody response to COVID vaccination,” she added. “However, some previous studies have shown some T-cell response to vaccination in these patients, and we are looking at that now.”
 

Assessing postvaccination antibody response

For the current study, the researchers analyzed the antibody response to COVID-19 vaccination at week 3, week 6, and month 3 after the first dose in 165 patients with MS and 200 healthy controls.

Of the patients with MS, 120 received both doses of mRNA vaccine and 42 received the AstraZeneca vaccine. The mean age of the MS patients was 45 years and 46 years in the healthy controls.

Adverse events were similar in the two groups, and no increase in relapse activity was seen in the patients with MS.

Mean antibody titers were slightly lower in the patients with MS versus the healthy controls. At 3 weeks, mean titers were 7,910 AU/mL in the patients with MS and 9,397 in the healthy controls. At 6 weeks, mean levels were 16,347 AU/mL in the patients with MS and 18,120 in the healthy controls.

Patients with MS treated with interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate, cladribine, and natalizumab who received mRNA vaccines developed a similar postvaccination humoral response as the healthy controls at each of 3, 6, and 12 weeks after the first dose.

Patients with MS receiving the AstraZeneca vaccine mounted a lower humoral response than those receiving the mRNA vaccine, but this same effect was also seen in the healthy controls.

However, patients on the anti-CD20 drugs ocrelizumab or rituximab showed a lower humoral response to COVID vaccination. Only 3 of 20 patients who had been treated with ocrelizumab developed antibodies, but these patients had longer washout periods (at least 6 months) between receiving ocrelizumab and the COVID vaccine. All six patients treated with rituximab had no antibody response to the COVID vaccination.

Dr. Oreja-Guevara suggested that ocrelizumab-treated patients may have a worse outcome after COVID-19 infection. “In the first wave of infection in Madrid, we recorded five patients on ocrelizumab with COVID-19, four of whom were hospitalized,” she noted.

“In patients on ocrelizumab we need to try and have a long interval between giving this drug and giving the COVID vaccine. The longer the washout period, the more antibodies are seen,” she said.

She noted that two patients in the study received the COVID vaccine 1 year after ocrelizumab administration and had a normal humoral response, similar to the healthy controls.

The new anti-CD20 drug, ofatumumab, did not seem to affect the COVID vaccine antibody response as much as ocrelizumab or rituximab. In the current study, four of five patients treated with ofatumumab had an antibody response.

Dr. Oreja-Guevara suggested that this was probably because the depletion of B cells is not so strong with ofatumumab. “This drug is dosed every 4 weeks and it doesn’t deplete all the B cells and they are replaced quite quickly.”

Fingolimod is another MS drug that seems to affect the antibody response to COVID-19 vaccination.

Dr. Oreja-Guevara described the response to COVID vaccination in patients on fingolimod as “very variable.” Of 16 patients treated with fingolimod, 4 failed to develop a humoral response, 7 had a low antibody response, and 5 had a similar response to that seen in the healthy controls (three of these patients had also had a previous COVID-19 infection). The response to vaccination in fingolimod-treated patients did not appear to be related to lymphopenia.
 

Cellular response also impaired with fingolimod

These data are consistent with those from another cohort from Israel reported previously.

In that study, which was published earlier in 2021, a team led by Anat Achiron, MD, Sheba Medical Center, Tel Aviv, analyzed humoral immunity in 125 patients with MS 1 month after the second dose of the Pfizer COVID vaccine. A group of healthy people similarly vaccinated served as control.

Results showed that protective humoral immunity occurred in 97.9% of the control group after vaccination, compared with 100% in untreated patients and 100% in patients treated with cladribine but in just 22.7% of those treated with ocrelizumab and only 3.8% of those taking fingolimod.

For ocrelizumab-treated patients, the failure to mount appropriate IgG immune response was regardless of the absolute lymphocyte counts that were in the normal range or to the time interval from the last ocrelizumab treatment dose that ranged from 3.1 to 8.9 months, “suggesting the need to postpone the next dosing to enable an effective postvaccination humoral response,” the authors said.

They noted that the majority of the fingolimod-treated patients in the study had a low lymphocyte count (<1,000 cells/mm³), which may be the cause for failing to mount an immune response. But even in the small group of fingolimod-treated MS patients with an absolute lymphocyte count above 1,000 cells/mm³, no humoral response was detected.

At the ECTRIMS meeting, Dr. Achiron presented further results from this study on memory B-cell and T-cell responses to the COVID vaccine in these patients.

The results showed that COVID-specific B- and T-cell responses were only present in about half of healthy subjects, untreated patients with MS, and those treated with cladribine.

While the B-cell response was almost completely impaired in the ocrelizumab-treated patients, the T-cell response was present to the same extent as in the control group. But fingolimod patients showed no B- or T-cell responses.

Dr. Achiron concluded that patients on ocrelizumab should wait at least 9 months following the last dose before receiving COVID vaccination, and that patients taking fingolimod should consider a switch to a different medication.

But she pointed out that, despite the lack of humoral cellular responses in the fingolimod group, in this study there does not seem to have been an increase in COVID infection in patients taking fingolimod in a large registry study.

“This leads us to the idea that maybe lymphopenia is not the only story, and maybe innate immunity is playing a role. We still don’t really know the answer for that.”

Dr. Achiron said she was also surprised to see that even untreated and healthy subjects did not develop complete B-cell and T-cell responses after double COVID vaccination. And similar results have been seen in patients who have recovered from natural COVID infection, where the B-cell response is “not 100%,” she added.

“This points to the suggestion that everyone might need a third vaccination, MS patients or not,” she concluded.

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

Scientists who speak about COVID-19 to the media or comment about the pandemic on social media often meet with harassment and abuse, according to a survey published in Nature.

The survey of 321 scientists, largely from the United States, the United Kingdom, and Germany, found that 22% were threatened with physical or sexual violence and that 15% received death threats.

More than one quarter of scientists surveyed said they “always” or “usually” received comments from trolls or were personally attacked after speaking out about COVID-19. More than 40% suffered emotional or psychological distress as a result.

Some scientists said the experience of being trolled online or receiving personal attacks had a chilling effect on their willingness to speak to the media in the future.

Even scientists who had a high profile before the COVID-19 pandemic said in the Nature article that the abuse was a “new and unwelcome phenomenon tied to the pandemic.”

Some scientists reported anonymously that they were hesitant to speak about some topics after witnessing the abuse received by others.
 

“Shocking” results require action

An editorial in Nature calls the results of the survey “shocking” and says institutions at all levels must do more to “protect and defend scientists, and to condemn intimidation.

“Intimidation is unacceptable on any scale, and the findings should be of concern to all those who care about scientists’ well-being. Such behavior also risks discouraging researchers from contributing to public discussion — which would be a huge loss, given their expertise, during the pandemic,” the editorial states.

“Scientists and health officials should expect their research to be questioned and challenged, and should welcome critical feedback that is given in good faith. But threats of violence and extreme online abuse do nothing to encourage debate — and risk undermining science communication at a time when it has never mattered more,” the editorial concludes.

A number of scientists weighed in on the survey in a statement from the U.K. nonprofit organization, Science Media Center.

“Undoubtedly there is a danger that scientists who have themselves been, or had colleagues who have been attacked in ways that disturb one’s equilibrium, may decide to disengage from the media. This will be sad and result in overall harm,” warned Stephen Evans, MSc, with the London School of Hygiene and Tropical Medicine.

Simon Clarke, PhD, with the University of Reading, who responded to the Nature survey, said he is “glad to see so many fellow scientists took the time to reflect on their experiences.”

Dr. Clarke said he is “shocked and saddened to hear that so many fellow scientists have experienced death threats or threats of physical or sexual violence, simply for doing their job trying to communicate the scientific facts that are so important for society in understanding and responding to this global health emergency.”

Dr. Clarke said he too has had some “bad experiences after appearing in the media, particularly after calling out conspiracy theorists and some politicians, who seem to dislike having their pet theories debunked. I have on occasion been threatened with various forms of death, violence and lifelong imprisonment. I am fortunate to have felt able to ignore the threats I’ve received, but I know that some colleagues have had far worse experiences.”

Michael Head, PhD, with the University of Southampton, said there’s been “a huge amount of abuse aimed at everyone contributing to the pandemic response. This has included NHS frontline staff, and also scientists and academics providing thoughts and explanatory comments to the public.

“I myself have received plenty of abuse throughout the pandemic. For those of us who have been pulling apart anti-vaccine misinformation from pre-pandemic times, the presence of these attempts at intimidation is very wearying, but not surprising,” said Dr. Head.

“As a white, male academic, I would imagine I’m far less likely to receive abuse than a scientist making similar points but from a different demographic,” he said.

Susan Michie, FMedSci, with the University College London, said the findings of harassment and abuse of scientists during the pandemic align closely with what she and many U.K. women colleagues who have been prominent in speaking to the media have endured.

“The online abuse occurs most intensively after media engagements and especially after those that address restrictions to social mixing, the wearing of face masks or vaccination,” Dr. Michie said.

“This abuse has not put off many women colleagues I know from speaking to the media,” she said. “I think this is because they are well established in their careers and/or brave and very committed to communicating scientific understanding.

“They have also set up a variety of networks to support each other. However, I am concerned that it discourages early career scientists, especially young women and young women from minoritized ethnic backgrounds, from engaging with the media,” she said.

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

Scientists who speak about COVID-19 to the media or comment about the pandemic on social media often meet with harassment and abuse, according to a survey published in Nature.

The survey of 321 scientists, largely from the United States, the United Kingdom, and Germany, found that 22% were threatened with physical or sexual violence and that 15% received death threats.

More than one quarter of scientists surveyed said they “always” or “usually” received comments from trolls or were personally attacked after speaking out about COVID-19. More than 40% suffered emotional or psychological distress as a result.

Some scientists said the experience of being trolled online or receiving personal attacks had a chilling effect on their willingness to speak to the media in the future.

Even scientists who had a high profile before the COVID-19 pandemic said in the Nature article that the abuse was a “new and unwelcome phenomenon tied to the pandemic.”

Some scientists reported anonymously that they were hesitant to speak about some topics after witnessing the abuse received by others.
 

“Shocking” results require action

An editorial in Nature calls the results of the survey “shocking” and says institutions at all levels must do more to “protect and defend scientists, and to condemn intimidation.

“Intimidation is unacceptable on any scale, and the findings should be of concern to all those who care about scientists’ well-being. Such behavior also risks discouraging researchers from contributing to public discussion — which would be a huge loss, given their expertise, during the pandemic,” the editorial states.

“Scientists and health officials should expect their research to be questioned and challenged, and should welcome critical feedback that is given in good faith. But threats of violence and extreme online abuse do nothing to encourage debate — and risk undermining science communication at a time when it has never mattered more,” the editorial concludes.

A number of scientists weighed in on the survey in a statement from the U.K. nonprofit organization, Science Media Center.

“Undoubtedly there is a danger that scientists who have themselves been, or had colleagues who have been attacked in ways that disturb one’s equilibrium, may decide to disengage from the media. This will be sad and result in overall harm,” warned Stephen Evans, MSc, with the London School of Hygiene and Tropical Medicine.

Simon Clarke, PhD, with the University of Reading, who responded to the Nature survey, said he is “glad to see so many fellow scientists took the time to reflect on their experiences.”

Dr. Clarke said he is “shocked and saddened to hear that so many fellow scientists have experienced death threats or threats of physical or sexual violence, simply for doing their job trying to communicate the scientific facts that are so important for society in understanding and responding to this global health emergency.”

Dr. Clarke said he too has had some “bad experiences after appearing in the media, particularly after calling out conspiracy theorists and some politicians, who seem to dislike having their pet theories debunked. I have on occasion been threatened with various forms of death, violence and lifelong imprisonment. I am fortunate to have felt able to ignore the threats I’ve received, but I know that some colleagues have had far worse experiences.”

Michael Head, PhD, with the University of Southampton, said there’s been “a huge amount of abuse aimed at everyone contributing to the pandemic response. This has included NHS frontline staff, and also scientists and academics providing thoughts and explanatory comments to the public.

“I myself have received plenty of abuse throughout the pandemic. For those of us who have been pulling apart anti-vaccine misinformation from pre-pandemic times, the presence of these attempts at intimidation is very wearying, but not surprising,” said Dr. Head.

“As a white, male academic, I would imagine I’m far less likely to receive abuse than a scientist making similar points but from a different demographic,” he said.

Susan Michie, FMedSci, with the University College London, said the findings of harassment and abuse of scientists during the pandemic align closely with what she and many U.K. women colleagues who have been prominent in speaking to the media have endured.

“The online abuse occurs most intensively after media engagements and especially after those that address restrictions to social mixing, the wearing of face masks or vaccination,” Dr. Michie said.

“This abuse has not put off many women colleagues I know from speaking to the media,” she said. “I think this is because they are well established in their careers and/or brave and very committed to communicating scientific understanding.

“They have also set up a variety of networks to support each other. However, I am concerned that it discourages early career scientists, especially young women and young women from minoritized ethnic backgrounds, from engaging with the media,” she said.

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

Scientists who speak about COVID-19 to the media or comment about the pandemic on social media often meet with harassment and abuse, according to a survey published in Nature.

The survey of 321 scientists, largely from the United States, the United Kingdom, and Germany, found that 22% were threatened with physical or sexual violence and that 15% received death threats.

More than one quarter of scientists surveyed said they “always” or “usually” received comments from trolls or were personally attacked after speaking out about COVID-19. More than 40% suffered emotional or psychological distress as a result.

Some scientists said the experience of being trolled online or receiving personal attacks had a chilling effect on their willingness to speak to the media in the future.

Even scientists who had a high profile before the COVID-19 pandemic said in the Nature article that the abuse was a “new and unwelcome phenomenon tied to the pandemic.”

Some scientists reported anonymously that they were hesitant to speak about some topics after witnessing the abuse received by others.
 

“Shocking” results require action

An editorial in Nature calls the results of the survey “shocking” and says institutions at all levels must do more to “protect and defend scientists, and to condemn intimidation.

“Intimidation is unacceptable on any scale, and the findings should be of concern to all those who care about scientists’ well-being. Such behavior also risks discouraging researchers from contributing to public discussion — which would be a huge loss, given their expertise, during the pandemic,” the editorial states.

“Scientists and health officials should expect their research to be questioned and challenged, and should welcome critical feedback that is given in good faith. But threats of violence and extreme online abuse do nothing to encourage debate — and risk undermining science communication at a time when it has never mattered more,” the editorial concludes.

A number of scientists weighed in on the survey in a statement from the U.K. nonprofit organization, Science Media Center.

“Undoubtedly there is a danger that scientists who have themselves been, or had colleagues who have been attacked in ways that disturb one’s equilibrium, may decide to disengage from the media. This will be sad and result in overall harm,” warned Stephen Evans, MSc, with the London School of Hygiene and Tropical Medicine.

Simon Clarke, PhD, with the University of Reading, who responded to the Nature survey, said he is “glad to see so many fellow scientists took the time to reflect on their experiences.”

Dr. Clarke said he is “shocked and saddened to hear that so many fellow scientists have experienced death threats or threats of physical or sexual violence, simply for doing their job trying to communicate the scientific facts that are so important for society in understanding and responding to this global health emergency.”

Dr. Clarke said he too has had some “bad experiences after appearing in the media, particularly after calling out conspiracy theorists and some politicians, who seem to dislike having their pet theories debunked. I have on occasion been threatened with various forms of death, violence and lifelong imprisonment. I am fortunate to have felt able to ignore the threats I’ve received, but I know that some colleagues have had far worse experiences.”

Michael Head, PhD, with the University of Southampton, said there’s been “a huge amount of abuse aimed at everyone contributing to the pandemic response. This has included NHS frontline staff, and also scientists and academics providing thoughts and explanatory comments to the public.

“I myself have received plenty of abuse throughout the pandemic. For those of us who have been pulling apart anti-vaccine misinformation from pre-pandemic times, the presence of these attempts at intimidation is very wearying, but not surprising,” said Dr. Head.

“As a white, male academic, I would imagine I’m far less likely to receive abuse than a scientist making similar points but from a different demographic,” he said.

Susan Michie, FMedSci, with the University College London, said the findings of harassment and abuse of scientists during the pandemic align closely with what she and many U.K. women colleagues who have been prominent in speaking to the media have endured.

“The online abuse occurs most intensively after media engagements and especially after those that address restrictions to social mixing, the wearing of face masks or vaccination,” Dr. Michie said.

“This abuse has not put off many women colleagues I know from speaking to the media,” she said. “I think this is because they are well established in their careers and/or brave and very committed to communicating scientific understanding.

“They have also set up a variety of networks to support each other. However, I am concerned that it discourages early career scientists, especially young women and young women from minoritized ethnic backgrounds, from engaging with the media,” she said.

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

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

Risk for Alzheimer’s disease (AD) and susceptibility to severe COVID-19 share a common genetic mechanism involved in the immune response to viruses, investigators report. The findings could lead to new treatment targets to slow progression and severity of both diseases.

Investigators found that a single genetic variant in the oligoadenylate synthetase 1 (OAS1) gene increases the risk for AD and that related variants in the same gene increase the likelihood of severe COVID-19 outcomes.

“These findings may allow us to identify new drug targets to slow progression of both diseases and reduce their severity,” Dervis Salih, PhD, senior research associate, UK Dementia Research Institute, University College London, said in an interview.

“Our work also suggests new approaches to treat both diseases with the same drugs,” Dr. Salih added.

The study was published online Oct. 7 in Brain.
 

Shared genetic network

The OAS1 gene is expressed in microglia, a type of immune cell that makes up around 10% of all cells in the brain.

In earlier work, investigators found evidence suggesting a link between the OAS1 gene and AD, but the function of the gene in microglia was unknown.

To further investigate the gene’s link to AD, they sequenced genetic data from 2,547 people – half with AD, and half without.

The genotyping analysis confirmed that the single-nucleotide polymorphism (SNP) rs1131454 within OAS1 is significantly associated with AD.

Given that the same OAS1 locus has recently been linked with severe COVID-19 outcomes, the researchers investigated four variants on the OAS1 gene.

Results indicate that SNPs within OAS1 associated with AD also show linkage to SNP variants associated with critical illness in COVID-19.

The rs1131454 (risk allele A) and rs4766676 (risk allele T) are associated with AD, and rs10735079 (risk allele A) and rs6489867 (risk allele T) are associated with critical illness with COVID-19, the investigators reported. All of these risk alleles dampen expression of OAS1.

“This study also provides strong new evidence that interferon signaling by the innate immune system plays a substantial role in the progression of Alzheimer’s,” said Dr. Salih.

“Identifying this shared genetic network in innate immune cells will allow us with future work to identify new biomarkers to track disease progression and also predict disease risk better for both disorders,” he added.
 

‘Fascinating’ link

In a statement from the UK nonprofit organization, Science Media Center, Kenneth Baillie, MBChB, with the University of Edinburgh, said this study builds on a discovery he and his colleagues made last year that OAS1 variants are associated with severe COVID-19.

“In the ISARIC4C study, we recently found that this is probably due to a change in the way cell membranes detect viruses, but this mechanism doesn’t explain the fascinating association with Alzheimer’s disease reported in this new work,” Dr. Baillie said.

“It is often the case that the same gene can have different roles in different parts of the body. Importantly, it doesn’t mean that having COVID-19 has any effect on your risk of Alzheimer’s,” he added.

Also weighing in on the new study, Jonathan Schott, MD, professor of neurology, University College London, noted that dementia is the “main preexisting health condition associated with COVID-19 mortality, accounting for about one in four deaths from COVID-19 between March and June 2020.

“While some of this excessive mortality may relate to people with dementia being overrepresented in care homes, which were particularly hard hit by the pandemic, or due to general increased vulnerability to infections, there have been questions as to whether there are common factors that might increase susceptibility both to developing dementia and to dying from COVID-19,” Dr. Schott explained.

This “elegant paper” provides evidence for the latter, “suggesting a common genetic mechanism both for Alzheimer’s disease and for severe COVID-19 infection,” Dr. Schott said.

“The identification of a genetic risk factor and elucidation of inflammatory pathways through which it may increase risk has important implications for our understanding of both diseases, with potential implications for novel treatments,” he added.

The study was funded by the UK Dementia Research Institute. The authors have disclosed no relevant financial relationships. Dr. Schott serves as chief medical officer for Alzheimer’s Research UK and is clinical adviser to the UK Dementia Research Institute. Dr. Baillie has disclosed no relevant financial relationships.

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

Risk for Alzheimer’s disease (AD) and susceptibility to severe COVID-19 share a common genetic mechanism involved in the immune response to viruses, investigators report. The findings could lead to new treatment targets to slow progression and severity of both diseases.

Investigators found that a single genetic variant in the oligoadenylate synthetase 1 (OAS1) gene increases the risk for AD and that related variants in the same gene increase the likelihood of severe COVID-19 outcomes.

“These findings may allow us to identify new drug targets to slow progression of both diseases and reduce their severity,” Dervis Salih, PhD, senior research associate, UK Dementia Research Institute, University College London, said in an interview.

“Our work also suggests new approaches to treat both diseases with the same drugs,” Dr. Salih added.

The study was published online Oct. 7 in Brain.
 

Shared genetic network

The OAS1 gene is expressed in microglia, a type of immune cell that makes up around 10% of all cells in the brain.

In earlier work, investigators found evidence suggesting a link between the OAS1 gene and AD, but the function of the gene in microglia was unknown.

To further investigate the gene’s link to AD, they sequenced genetic data from 2,547 people – half with AD, and half without.

The genotyping analysis confirmed that the single-nucleotide polymorphism (SNP) rs1131454 within OAS1 is significantly associated with AD.

Given that the same OAS1 locus has recently been linked with severe COVID-19 outcomes, the researchers investigated four variants on the OAS1 gene.

Results indicate that SNPs within OAS1 associated with AD also show linkage to SNP variants associated with critical illness in COVID-19.

The rs1131454 (risk allele A) and rs4766676 (risk allele T) are associated with AD, and rs10735079 (risk allele A) and rs6489867 (risk allele T) are associated with critical illness with COVID-19, the investigators reported. All of these risk alleles dampen expression of OAS1.

“This study also provides strong new evidence that interferon signaling by the innate immune system plays a substantial role in the progression of Alzheimer’s,” said Dr. Salih.

“Identifying this shared genetic network in innate immune cells will allow us with future work to identify new biomarkers to track disease progression and also predict disease risk better for both disorders,” he added.
 

‘Fascinating’ link

In a statement from the UK nonprofit organization, Science Media Center, Kenneth Baillie, MBChB, with the University of Edinburgh, said this study builds on a discovery he and his colleagues made last year that OAS1 variants are associated with severe COVID-19.

“In the ISARIC4C study, we recently found that this is probably due to a change in the way cell membranes detect viruses, but this mechanism doesn’t explain the fascinating association with Alzheimer’s disease reported in this new work,” Dr. Baillie said.

“It is often the case that the same gene can have different roles in different parts of the body. Importantly, it doesn’t mean that having COVID-19 has any effect on your risk of Alzheimer’s,” he added.

Also weighing in on the new study, Jonathan Schott, MD, professor of neurology, University College London, noted that dementia is the “main preexisting health condition associated with COVID-19 mortality, accounting for about one in four deaths from COVID-19 between March and June 2020.

“While some of this excessive mortality may relate to people with dementia being overrepresented in care homes, which were particularly hard hit by the pandemic, or due to general increased vulnerability to infections, there have been questions as to whether there are common factors that might increase susceptibility both to developing dementia and to dying from COVID-19,” Dr. Schott explained.

This “elegant paper” provides evidence for the latter, “suggesting a common genetic mechanism both for Alzheimer’s disease and for severe COVID-19 infection,” Dr. Schott said.

“The identification of a genetic risk factor and elucidation of inflammatory pathways through which it may increase risk has important implications for our understanding of both diseases, with potential implications for novel treatments,” he added.

The study was funded by the UK Dementia Research Institute. The authors have disclosed no relevant financial relationships. Dr. Schott serves as chief medical officer for Alzheimer’s Research UK and is clinical adviser to the UK Dementia Research Institute. Dr. Baillie has disclosed no relevant financial relationships.

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

Risk for Alzheimer’s disease (AD) and susceptibility to severe COVID-19 share a common genetic mechanism involved in the immune response to viruses, investigators report. The findings could lead to new treatment targets to slow progression and severity of both diseases.

Investigators found that a single genetic variant in the oligoadenylate synthetase 1 (OAS1) gene increases the risk for AD and that related variants in the same gene increase the likelihood of severe COVID-19 outcomes.

“These findings may allow us to identify new drug targets to slow progression of both diseases and reduce their severity,” Dervis Salih, PhD, senior research associate, UK Dementia Research Institute, University College London, said in an interview.

“Our work also suggests new approaches to treat both diseases with the same drugs,” Dr. Salih added.

The study was published online Oct. 7 in Brain.
 

Shared genetic network

The OAS1 gene is expressed in microglia, a type of immune cell that makes up around 10% of all cells in the brain.

In earlier work, investigators found evidence suggesting a link between the OAS1 gene and AD, but the function of the gene in microglia was unknown.

To further investigate the gene’s link to AD, they sequenced genetic data from 2,547 people – half with AD, and half without.

The genotyping analysis confirmed that the single-nucleotide polymorphism (SNP) rs1131454 within OAS1 is significantly associated with AD.

Given that the same OAS1 locus has recently been linked with severe COVID-19 outcomes, the researchers investigated four variants on the OAS1 gene.

Results indicate that SNPs within OAS1 associated with AD also show linkage to SNP variants associated with critical illness in COVID-19.

The rs1131454 (risk allele A) and rs4766676 (risk allele T) are associated with AD, and rs10735079 (risk allele A) and rs6489867 (risk allele T) are associated with critical illness with COVID-19, the investigators reported. All of these risk alleles dampen expression of OAS1.

“This study also provides strong new evidence that interferon signaling by the innate immune system plays a substantial role in the progression of Alzheimer’s,” said Dr. Salih.

“Identifying this shared genetic network in innate immune cells will allow us with future work to identify new biomarkers to track disease progression and also predict disease risk better for both disorders,” he added.
 

‘Fascinating’ link

In a statement from the UK nonprofit organization, Science Media Center, Kenneth Baillie, MBChB, with the University of Edinburgh, said this study builds on a discovery he and his colleagues made last year that OAS1 variants are associated with severe COVID-19.

“In the ISARIC4C study, we recently found that this is probably due to a change in the way cell membranes detect viruses, but this mechanism doesn’t explain the fascinating association with Alzheimer’s disease reported in this new work,” Dr. Baillie said.

“It is often the case that the same gene can have different roles in different parts of the body. Importantly, it doesn’t mean that having COVID-19 has any effect on your risk of Alzheimer’s,” he added.

Also weighing in on the new study, Jonathan Schott, MD, professor of neurology, University College London, noted that dementia is the “main preexisting health condition associated with COVID-19 mortality, accounting for about one in four deaths from COVID-19 between March and June 2020.

“While some of this excessive mortality may relate to people with dementia being overrepresented in care homes, which were particularly hard hit by the pandemic, or due to general increased vulnerability to infections, there have been questions as to whether there are common factors that might increase susceptibility both to developing dementia and to dying from COVID-19,” Dr. Schott explained.

This “elegant paper” provides evidence for the latter, “suggesting a common genetic mechanism both for Alzheimer’s disease and for severe COVID-19 infection,” Dr. Schott said.

“The identification of a genetic risk factor and elucidation of inflammatory pathways through which it may increase risk has important implications for our understanding of both diseases, with potential implications for novel treatments,” he added.

The study was funded by the UK Dementia Research Institute. The authors have disclosed no relevant financial relationships. Dr. Schott serves as chief medical officer for Alzheimer’s Research UK and is clinical adviser to the UK Dementia Research Institute. Dr. Baillie has disclosed no relevant financial relationships.

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

The chances that unvaccinated family members will be infected or hospitalized with COVID-19 drop sharply if even one family member is vaccinated. The chances are reduced even further with each additional vaccinated or otherwise immune family member, according to new data.

Lead author Peter Nordström, MD, PhD, with the unit of geriatric medicine, Umeå (Sweden) University, said in an interview the message is important for public health: “When you vaccinate, you do not just protect yourself but also your relatives.”

The findings were published online on Oct. 11, 2021, in JAMA Internal Medicine.

Researchers analyzed data from 1,789,728 individuals from 814,806 families from nationwide registries in Sweden. All individuals had acquired immunity either from previously being infected with SARS-CoV-2 or by being fully vaccinated (that is, having received two doses of the Moderna, Pfizer, or Oxford/AstraZeneca vaccines). Persons were considered for inclusion until May 26, 2021.

Each person with immunity was matched in a 1:1 ratio to a person without immunity from a cohort of individuals with families that had from two to five members. Families with more than five members were excluded because of small sample sizes.

Primarily nonimmune families in which there was one immune family member had a 45%-61% lower risk of contracting COVID-19 (hazard ratio, 0.39-0.55; 95% confidence interval, 0.37-0.61; P < .001).

The risk reduction increased to 75%-86% when two family members were immune (HR, 0.14-0.25; 95% CI, 0.11-0.27; P < .001).

It increased to 91%-94% when three family members were immune (HR, 0.06-0.09; 95% CI, 0.04-0.10; P < .001) and to 97% with four immune family members (HR, 0.03; 95% CI, 0.02-0.05; P < .001).

“The results were similar for the outcome of COVID-19 infection that was severe enough to warrant a hospital stay,” the authors wrote. They listed as an example that, in three-member families in which two members were immune, the remaining nonimmune family member had an 80% lower risk for hospitalization (HR, 0.20; 95% CI, 0.10-0.43; P < .001).
 

Global implications

Dr. Nordström said the team used the family setting because it was more easily identifiable as a cohort with the national registries and because COVID-19 is spread among people in close contact with each other. The findings have implications for other groups that spend large amounts of time together and for herd immunity, he added.

The findings may be particularly welcome in regions of the world where vaccination rates are very low. The authors noted that most of the global population has not yet been vaccinated and that “it is anticipated that most of the population in low-income countries will be unable to receive a vaccine in 2021, with current vaccination rates suggesting that completely inoculating 70%-85% of the global population may take up to 5 years.”

Jill Foster, MD, a pediatric infectious disease specialist at the University of Minnesota, Minneapolis, said in an interview she agrees that the news could encourage countries that have very low vaccination rates.

This study may help motivate areas with few resources to start small, she said: “Even one is better than zero.”

She added that this news could also help ease the minds of families that have immunocompromised members or in which there are children who are too young to be vaccinated.

With these data, she said, people can see there’s something they can do to help protect a family member.

Dr. Foster said that although it’s intuitive to think that the more vaccinated people there are in a family, the safer people are, “it’s really nice to see the data coming out of such a large dataset.”

The authors acknowledged that a limitation of the study is that, at the time the study was conducted, the Delta variant was uncommon in Sweden. It is therefore unclear whether the findings regarding immunity are still relevant in Sweden and elsewhere now that the Delta strain is dominant.

The authors reported no relevant financial relationships. Dr. Foster has received grant support from Moderna.

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

The chances that unvaccinated family members will be infected or hospitalized with COVID-19 drop sharply if even one family member is vaccinated. The chances are reduced even further with each additional vaccinated or otherwise immune family member, according to new data.

Lead author Peter Nordström, MD, PhD, with the unit of geriatric medicine, Umeå (Sweden) University, said in an interview the message is important for public health: “When you vaccinate, you do not just protect yourself but also your relatives.”

The findings were published online on Oct. 11, 2021, in JAMA Internal Medicine.

Researchers analyzed data from 1,789,728 individuals from 814,806 families from nationwide registries in Sweden. All individuals had acquired immunity either from previously being infected with SARS-CoV-2 or by being fully vaccinated (that is, having received two doses of the Moderna, Pfizer, or Oxford/AstraZeneca vaccines). Persons were considered for inclusion until May 26, 2021.

Each person with immunity was matched in a 1:1 ratio to a person without immunity from a cohort of individuals with families that had from two to five members. Families with more than five members were excluded because of small sample sizes.

Primarily nonimmune families in which there was one immune family member had a 45%-61% lower risk of contracting COVID-19 (hazard ratio, 0.39-0.55; 95% confidence interval, 0.37-0.61; P < .001).

The risk reduction increased to 75%-86% when two family members were immune (HR, 0.14-0.25; 95% CI, 0.11-0.27; P < .001).

It increased to 91%-94% when three family members were immune (HR, 0.06-0.09; 95% CI, 0.04-0.10; P < .001) and to 97% with four immune family members (HR, 0.03; 95% CI, 0.02-0.05; P < .001).

“The results were similar for the outcome of COVID-19 infection that was severe enough to warrant a hospital stay,” the authors wrote. They listed as an example that, in three-member families in which two members were immune, the remaining nonimmune family member had an 80% lower risk for hospitalization (HR, 0.20; 95% CI, 0.10-0.43; P < .001).
 

Global implications

Dr. Nordström said the team used the family setting because it was more easily identifiable as a cohort with the national registries and because COVID-19 is spread among people in close contact with each other. The findings have implications for other groups that spend large amounts of time together and for herd immunity, he added.

The findings may be particularly welcome in regions of the world where vaccination rates are very low. The authors noted that most of the global population has not yet been vaccinated and that “it is anticipated that most of the population in low-income countries will be unable to receive a vaccine in 2021, with current vaccination rates suggesting that completely inoculating 70%-85% of the global population may take up to 5 years.”

Jill Foster, MD, a pediatric infectious disease specialist at the University of Minnesota, Minneapolis, said in an interview she agrees that the news could encourage countries that have very low vaccination rates.

This study may help motivate areas with few resources to start small, she said: “Even one is better than zero.”

She added that this news could also help ease the minds of families that have immunocompromised members or in which there are children who are too young to be vaccinated.

With these data, she said, people can see there’s something they can do to help protect a family member.

Dr. Foster said that although it’s intuitive to think that the more vaccinated people there are in a family, the safer people are, “it’s really nice to see the data coming out of such a large dataset.”

The authors acknowledged that a limitation of the study is that, at the time the study was conducted, the Delta variant was uncommon in Sweden. It is therefore unclear whether the findings regarding immunity are still relevant in Sweden and elsewhere now that the Delta strain is dominant.

The authors reported no relevant financial relationships. Dr. Foster has received grant support from Moderna.

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

The chances that unvaccinated family members will be infected or hospitalized with COVID-19 drop sharply if even one family member is vaccinated. The chances are reduced even further with each additional vaccinated or otherwise immune family member, according to new data.

Lead author Peter Nordström, MD, PhD, with the unit of geriatric medicine, Umeå (Sweden) University, said in an interview the message is important for public health: “When you vaccinate, you do not just protect yourself but also your relatives.”

The findings were published online on Oct. 11, 2021, in JAMA Internal Medicine.

Researchers analyzed data from 1,789,728 individuals from 814,806 families from nationwide registries in Sweden. All individuals had acquired immunity either from previously being infected with SARS-CoV-2 or by being fully vaccinated (that is, having received two doses of the Moderna, Pfizer, or Oxford/AstraZeneca vaccines). Persons were considered for inclusion until May 26, 2021.

Each person with immunity was matched in a 1:1 ratio to a person without immunity from a cohort of individuals with families that had from two to five members. Families with more than five members were excluded because of small sample sizes.

Primarily nonimmune families in which there was one immune family member had a 45%-61% lower risk of contracting COVID-19 (hazard ratio, 0.39-0.55; 95% confidence interval, 0.37-0.61; P < .001).

The risk reduction increased to 75%-86% when two family members were immune (HR, 0.14-0.25; 95% CI, 0.11-0.27; P < .001).

It increased to 91%-94% when three family members were immune (HR, 0.06-0.09; 95% CI, 0.04-0.10; P < .001) and to 97% with four immune family members (HR, 0.03; 95% CI, 0.02-0.05; P < .001).

“The results were similar for the outcome of COVID-19 infection that was severe enough to warrant a hospital stay,” the authors wrote. They listed as an example that, in three-member families in which two members were immune, the remaining nonimmune family member had an 80% lower risk for hospitalization (HR, 0.20; 95% CI, 0.10-0.43; P < .001).
 

Global implications

Dr. Nordström said the team used the family setting because it was more easily identifiable as a cohort with the national registries and because COVID-19 is spread among people in close contact with each other. The findings have implications for other groups that spend large amounts of time together and for herd immunity, he added.

The findings may be particularly welcome in regions of the world where vaccination rates are very low. The authors noted that most of the global population has not yet been vaccinated and that “it is anticipated that most of the population in low-income countries will be unable to receive a vaccine in 2021, with current vaccination rates suggesting that completely inoculating 70%-85% of the global population may take up to 5 years.”

Jill Foster, MD, a pediatric infectious disease specialist at the University of Minnesota, Minneapolis, said in an interview she agrees that the news could encourage countries that have very low vaccination rates.

This study may help motivate areas with few resources to start small, she said: “Even one is better than zero.”

She added that this news could also help ease the minds of families that have immunocompromised members or in which there are children who are too young to be vaccinated.

With these data, she said, people can see there’s something they can do to help protect a family member.

Dr. Foster said that although it’s intuitive to think that the more vaccinated people there are in a family, the safer people are, “it’s really nice to see the data coming out of such a large dataset.”

The authors acknowledged that a limitation of the study is that, at the time the study was conducted, the Delta variant was uncommon in Sweden. It is therefore unclear whether the findings regarding immunity are still relevant in Sweden and elsewhere now that the Delta strain is dominant.

The authors reported no relevant financial relationships. Dr. Foster has received grant support from Moderna.

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

Schools without mask requirements were three-and-a-half times more likely to have COVID-19 outbreaks than those enforcing mask mandates, according to new Centers for Disease Control and Prevention research.

The study, which focused on 1,000 schools in Arizona’s Maricopa and Pima counties, found that there were 113 COVID-19 outbreaks in schools without mask requirements in the first month of in-person learning. There were 16 outbreaks in schools with mask requirements.

“Masks in schools work to protect our children, to keep them and their school communities safe, and to keep them in school for in-person learning,” CDC Director Rochelle Walensky, MD, said at an Oct. 13 White House briefing.

But, she said, more than 95% of schools across the country had remained open through the end of September, despite 1,800 school closures affecting nearly 1 million students.

Protection for children in school is just one piece of the puzzle, Dr. Walensky said – there must also be COVID-safe practices at home to limit transmission. A CDC study published in October found that children had similar infection rates, compared with adults, confirming there is risk to people of all ages.

“For those children not yet eligible for vaccination, the best protection we can provide them is to make sure everyone around them in the household is vaccinated and to make sure they’re wearing a mask in school and during indoor extracurricular activities,” Dr. Walensky said.

Meanwhile, Pfizer’s vaccine for children ages 5-11 may be approved by early November. The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee will meet Oct. 26 to discuss available data, and the CDC’s Advisory Committee on Immunization Practices will meet Nov. 2. A decision is expected soon after.

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

Schools without mask requirements were three-and-a-half times more likely to have COVID-19 outbreaks than those enforcing mask mandates, according to new Centers for Disease Control and Prevention research.

The study, which focused on 1,000 schools in Arizona’s Maricopa and Pima counties, found that there were 113 COVID-19 outbreaks in schools without mask requirements in the first month of in-person learning. There were 16 outbreaks in schools with mask requirements.

“Masks in schools work to protect our children, to keep them and their school communities safe, and to keep them in school for in-person learning,” CDC Director Rochelle Walensky, MD, said at an Oct. 13 White House briefing.

But, she said, more than 95% of schools across the country had remained open through the end of September, despite 1,800 school closures affecting nearly 1 million students.

Protection for children in school is just one piece of the puzzle, Dr. Walensky said – there must also be COVID-safe practices at home to limit transmission. A CDC study published in October found that children had similar infection rates, compared with adults, confirming there is risk to people of all ages.

“For those children not yet eligible for vaccination, the best protection we can provide them is to make sure everyone around them in the household is vaccinated and to make sure they’re wearing a mask in school and during indoor extracurricular activities,” Dr. Walensky said.

Meanwhile, Pfizer’s vaccine for children ages 5-11 may be approved by early November. The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee will meet Oct. 26 to discuss available data, and the CDC’s Advisory Committee on Immunization Practices will meet Nov. 2. A decision is expected soon after.

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

Schools without mask requirements were three-and-a-half times more likely to have COVID-19 outbreaks than those enforcing mask mandates, according to new Centers for Disease Control and Prevention research.

The study, which focused on 1,000 schools in Arizona’s Maricopa and Pima counties, found that there were 113 COVID-19 outbreaks in schools without mask requirements in the first month of in-person learning. There were 16 outbreaks in schools with mask requirements.

“Masks in schools work to protect our children, to keep them and their school communities safe, and to keep them in school for in-person learning,” CDC Director Rochelle Walensky, MD, said at an Oct. 13 White House briefing.

But, she said, more than 95% of schools across the country had remained open through the end of September, despite 1,800 school closures affecting nearly 1 million students.

Protection for children in school is just one piece of the puzzle, Dr. Walensky said – there must also be COVID-safe practices at home to limit transmission. A CDC study published in October found that children had similar infection rates, compared with adults, confirming there is risk to people of all ages.

“For those children not yet eligible for vaccination, the best protection we can provide them is to make sure everyone around them in the household is vaccinated and to make sure they’re wearing a mask in school and during indoor extracurricular activities,” Dr. Walensky said.

Meanwhile, Pfizer’s vaccine for children ages 5-11 may be approved by early November. The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee will meet Oct. 26 to discuss available data, and the CDC’s Advisory Committee on Immunization Practices will meet Nov. 2. A decision is expected soon after.

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

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.