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As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

As COVID-19 cases surge and vaccinations lag, health authorities continue to seek additional ways to mitigate the spread of the novel coronavirus.

Now, a modeling study estimates that more than half of transmissions come from pre-, never-, and asymptomatic individuals, indicating that symptom-based screening will have little effect on spread.

Courtesy NIAID

The analysis

Based on data from several COVID-19 studies from last year, the CDC’s analytical model assumes at baseline that infectiousness peaks at the median point of symptom onset, and that 30% of infected individuals never develop symptoms but are nevertheless 75% as infectious as those who develop overt symptoms.

The investigators then model multiple scenarios of transmission based pre- and never-symptomatic individuals, assuming different incubation and infectious periods, and varying numbers of days from point of infection to symptom onset.

When combined, the models predicts that 59% of all transmission would come from asymptomatic transmission – 35% from presymptomatic individuals and 24% from never-symptomatic individuals.

The findings complement those of an earlier CDC analysis, according to the authors.

The overall proportion of transmission from presymptomatic and never-symptomatic individuals is key to identifying mitigation measures that may be able to control SARS-CoV-2, the authors stated.

For example, they explain, if the infection reproduction number (R) in a particular setting is 2.0, a reduction in transmission of at least 50% is needed in order to reduce R to below 1.0. “Given that in some settings R is likely much greater than 2 and more than half of transmissions may come from individuals who are asymptomatic at the time of transmission, effective control must mitigate transmission risk from people without symptoms,” they wrote.

The authors acknowledge that the study applies a simplistic model to a complex and evolving phenomenon, and that the exact proportions of presymptomatic and never-symptomatic transmission and the incubation periods are not known. They also note symptoms and transmissions appear to vary across different population groups, with older individuals more likely than younger persons to experience symptoms, according to previous studies.

“Assume that everyone is potentially infected”

Other experts agree that expanded testing of asymptomatic individuals is important. “Screening for fever and isolation of symptomatic individuals is a common-sense approach to help prevent spread, but these measures are by no means adequate since it’s been clearly documented that individuals who are either asymptomatic or presymptomatic can still spread the virus,” said Brett Williams, MD, an infectious disease specialist and assistant professor of medicine at Rush University in Chicago. 

“As we saw with the White House Rose Garden superspreader outbreak, testing does not reliably exclude infection either because the tested individual has not yet become positive or the test is falsely negative,” Dr. Williams, who was not involved in the CDC study, said in an interview. He further noted that when prevalence is as high as it currently is in the United States, the rate of false negatives will be high because a large proportion of those screened will be unknowingly infected.

At his center, all visitors and staff are screened with a temperature probe on entry, and since the earliest days of the pandemic, universal masking has been required. “Nationally there have been many instances of hospital break room outbreaks because of staff eating lunch together, and these outbreaks also demonstrate the incompleteness of symptomatic isolation,” Dr. Williams said.

For his part, virologist Frank Esper, MD, a pediatric infectious disease specialist at the Cleveland Clinic, said that while it’s been understood for some time that many infected people will not exhibit symptoms, “the question that remains is just how infectious are they?”

Dr. Esper’s takeaway from the modeling study is not so much that we need more screening of possibly exposed but asymptomatic people, but rather testing symptomatic people and tracing their contacts is not enough.

“We need to continue to assume that everyone is potentially infected whether they know it or not. And even though we have ramped up our testing to a much greater capacity than in the first wave, we need to continue to wear masks and socially distance because just identifying people who are sick and isolating or quarantining them is not going to be enough to contain the pandemic.”

And although assumption-based modeling is helpful, it cannot tell us “how many asymptomatic people are actually infected,” said Dr. Esper, who was not involved in the CDC study.

Dr. Esper also pointed out that the study estimates are based on data from early Chinese studies, but the virus has since changed. The new, more transmissible strain in the United States and elsewhere may involve not only more infections but also a longer presymptomatic stage. “So the CDC study may actually undershoot asymptomatic infections,” he said. 

He also agreed with the authors that when it comes to infection, not all humans are equal. “Older people tend to be more symptomatic and become symptomatic more quickly so the asymptomatic rate is not the same across board from young people age 20 to older people.”

The bottom line, said David. A. Hirschwerk, MD, an infectious disease specialist at Northwell Health in Manhasset, N.Y., is that these data support the maintenance of protective measures we’ve been taking over the past months. “They support the concept that asymptomatic people are a significant source of transmission and that we need to adhere to mask wearing and social distancing, particularly indoors,” Dr. Hirschwerk, who was not involved in the analysis, said in an interview. “More testing would be better but it has to be fast and it has to be efficient, and there are a lot of challenges to overcome.”

The study was done as part of the CDC’s coronavirus disease 2019 response and was supported solely by federal base and response funding. The authors and commentators have disclosed no relevant financial relationships.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Health care providers should be ready to treat rare cases of anaphylaxis following administration of COVID-19 vaccines, federal medical officials have urged. The officials also stressed the importance of continuing vaccinations, despite reports of the rare side effect.

There have been 29 cases of anaphylaxis to date following administration of a COVID-19 vaccine, officials from the Centers for Disease Control and Prevention said in a call with reporters on Jan. 6.

The severe allergic reaction, which appears to be rare, can happen with either the Pfizer-BioNTech vaccine or the rival Moderna product. The Food and Drug Administration granted emergency use authorizations for these two vaccines in December.

Even with the cases seen to date, the COVID-19 vaccines remain a “good value proposition,” Nancy Messonnier, MD, director of the CDC’s National Center for Immunization, said in the call.

There have been about 11.1 cases of anaphylaxis per million doses with the Pfizer-BioNTech COVID-19 vaccine, which is higher than the estimated 1.3 cases per million doses with influenza vaccines, she said. But the low risk of anaphylaxis must be balanced against the threat of COVID-19, which currently claims about 2,000 lives a day in the United States, she said. In addition, many people are reporting long-term complications with COVID-19 even if they recover.

Kept in context, the data on anaphylaxis should not scare people away from getting a COVID-19 vaccine, she added.

“Their risk from COVID and poor outcomes is still more than the risk of a severe outcome from the vaccine,” Dr. Messonnier said. “And fortunately, we know how to treat anaphylaxis.”

Dr. Messonnier urged health care workers administering COVID-19 vaccines to be prepared.

“Anybody administering vaccines needs not just to have the EpiPen available, but frankly, to know how to use it,” Dr. Messonnier said.
 

MMWR details

The CDC on Jan. 6 also provided an update on anaphylaxis in Morbidity and Mortality Weekly Report (MMWR).

The information included in the report was based on cases reported with the Pfizer-BioNTech vaccine – the first to get emergency use authorization from the FDA. On the call with reporters, CDC officials confirmed there have been additional reports since then and anaphylaxis has been reported with both the Pfizer-BioNTech and Moderna vaccines. CDC officials said they could not give a breakdown of how many cases were linked to each of these products at this time.

Between Dec. 14 and 23, 2020, monitoring by the Vaccine Adverse Event Reporting System detected 21 cases of anaphylaxis after administration of a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine. Most reactions – 71% – occurred within 15 minutes of vaccination.

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

Children and adolescents who receive positive COVID-19 test results are not only more likely to have been in close contact with someone with a confirmed case of the virus but also are less likely to have reported consistent mask use among students and staff inside the school they attended, reported Charlotte V. Hobbs, MD, and colleagues at the University of Mississippi, Jackson.

FluxFactory/E+

Nearly two-thirds reported that exposure came from family members

Of the total study participants observed, 82 (21%) were under 4 years of age; 214 (54%) were female; 217 (55%) were non-Hispanic black, and 145 (37%) were non-Hispanic white. More than half (53%) sought testing because of COVID-19 symptoms. Of those who tested positive, 66% reported having come into close contact with a COVID-19 case, and 64% reported that those contacts were family members, compared with 15% of contacts who were schoolmates and 27% who were child care classmates.

All participants completed in-person school or child care attendance less than 14 days before testing positive for the virus, including 62% of patients testing positive and 68% of those testing negative. The authors noted that school attendance itself was not found to be associated with any positive test results. In fact, parents in 64% of positive cases and 76% of negative cases reported mask wearing among children and staff inside places of learning.

Of those study participants testing positive who did come into close contact with someone with COVID-19, the contacts were more likely to be family members than school or child care classmates. Specifically, they were more likely, in the 2-week period preceding testing, to have attended gatherings with individuals outside their immediate households, including social events and activities with other children. Parents of students testing positive were also less likely to report consistent indoor mask use among their children older than 2 years and school staff members.

School attendance was not found to increase likelihood of testing positive

Attending in-person school or child care during the 2 weeks before the SARS-CoV-2 test was not associated with greater likelihood of testing positive, the study authors noted, adding that the majority of study respondents reported universal mask use inside school and child care facilities, consistent with Mississippi State Department of Health recommended guidelines.

Dr. Hobbs and colleagues reported at least four limitations of the study. They noted that the study participants may not be representative of youth in other geographic regions of the country. They considered the possibility of unmeasured confounding of participant behaviors that may not have been factored into the study. No attempt was made to verify parent claims of mask use at schools and child care programs. Lastly, they acknowledged that “case or control status might be subject to misclassification because of imperfect sensitivity or specificity of PCR-based testing.

As of Dec. 14, 2020, the CDC reported that 10.2% of all COVID-19 cases in the United States were in children and adolescents under the age of 18.

“Continued efforts to prevent transmission at schools and child care programs are important, as are assessments of various types of activities and exposures to identify risk factors for COVID-19 as children engage in classroom and social interactions.” Promoting behaviors to reduce exposures to the virus among youth in the household, the community, schools, and child care programs is important to preventing outbreaks of the virus at schools, the authors cautioned.

In a separate interview with this news organization, Karalyn Kinsella, MD, general pediatrician in a small group private practice in Cheshire, Conn., said, “What this report tells me is that COVID cases are more common when mask use is inconsistent in schools and at home and in schools that don’t properly adhere to CDC guidelines. Overall, so long as social distancing guidelines are followed, schools are pretty safe places for kids during this pandemic.”

This finding is important, since many families are keeping their children out of school over fears of contracting the virus, she added. Some of the consequences these children are suffering include a lack of social connection and structure, which in some cases is leading to worsening anxiety and depression, and for those with disabilities, such as those who receive physical therapy, occupational therapy, speech or have IEPs, they’re not getting the full benefit of the services that they would otherwise receive in person, she observed.

“I don’t think families really understand the risks of getting together with family or friends “in their bubble” or the risk of continuing sports participation. This is where the majority of COVID cases are coming from,” she said, adding that it is important to discuss this risk with them at appointments. So, when families ask us what we think of in-person learning, I think we should feel fairly confident that the benefit may outweigh the risk.”

Dr. Hobbs and colleagues, and Dr. Kinsella, had no conflicts of interest to report.

[email protected]

SOURCE: MMWR Morb Mortal Wkly Rep. 2020;69:1925-9. doi: 10.15585/mmwr.mm6950e3.

Children and adolescents who receive positive COVID-19 test results are not only more likely to have been in close contact with someone with a confirmed case of the virus but also are less likely to have reported consistent mask use among students and staff inside the school they attended, reported Charlotte V. Hobbs, MD, and colleagues at the University of Mississippi, Jackson.

FluxFactory/E+

Nearly two-thirds reported that exposure came from family members

Of the total study participants observed, 82 (21%) were under 4 years of age; 214 (54%) were female; 217 (55%) were non-Hispanic black, and 145 (37%) were non-Hispanic white. More than half (53%) sought testing because of COVID-19 symptoms. Of those who tested positive, 66% reported having come into close contact with a COVID-19 case, and 64% reported that those contacts were family members, compared with 15% of contacts who were schoolmates and 27% who were child care classmates.

All participants completed in-person school or child care attendance less than 14 days before testing positive for the virus, including 62% of patients testing positive and 68% of those testing negative. The authors noted that school attendance itself was not found to be associated with any positive test results. In fact, parents in 64% of positive cases and 76% of negative cases reported mask wearing among children and staff inside places of learning.

Of those study participants testing positive who did come into close contact with someone with COVID-19, the contacts were more likely to be family members than school or child care classmates. Specifically, they were more likely, in the 2-week period preceding testing, to have attended gatherings with individuals outside their immediate households, including social events and activities with other children. Parents of students testing positive were also less likely to report consistent indoor mask use among their children older than 2 years and school staff members.

School attendance was not found to increase likelihood of testing positive

Attending in-person school or child care during the 2 weeks before the SARS-CoV-2 test was not associated with greater likelihood of testing positive, the study authors noted, adding that the majority of study respondents reported universal mask use inside school and child care facilities, consistent with Mississippi State Department of Health recommended guidelines.

Dr. Hobbs and colleagues reported at least four limitations of the study. They noted that the study participants may not be representative of youth in other geographic regions of the country. They considered the possibility of unmeasured confounding of participant behaviors that may not have been factored into the study. No attempt was made to verify parent claims of mask use at schools and child care programs. Lastly, they acknowledged that “case or control status might be subject to misclassification because of imperfect sensitivity or specificity of PCR-based testing.

As of Dec. 14, 2020, the CDC reported that 10.2% of all COVID-19 cases in the United States were in children and adolescents under the age of 18.

“Continued efforts to prevent transmission at schools and child care programs are important, as are assessments of various types of activities and exposures to identify risk factors for COVID-19 as children engage in classroom and social interactions.” Promoting behaviors to reduce exposures to the virus among youth in the household, the community, schools, and child care programs is important to preventing outbreaks of the virus at schools, the authors cautioned.

In a separate interview with this news organization, Karalyn Kinsella, MD, general pediatrician in a small group private practice in Cheshire, Conn., said, “What this report tells me is that COVID cases are more common when mask use is inconsistent in schools and at home and in schools that don’t properly adhere to CDC guidelines. Overall, so long as social distancing guidelines are followed, schools are pretty safe places for kids during this pandemic.”

This finding is important, since many families are keeping their children out of school over fears of contracting the virus, she added. Some of the consequences these children are suffering include a lack of social connection and structure, which in some cases is leading to worsening anxiety and depression, and for those with disabilities, such as those who receive physical therapy, occupational therapy, speech or have IEPs, they’re not getting the full benefit of the services that they would otherwise receive in person, she observed.

“I don’t think families really understand the risks of getting together with family or friends “in their bubble” or the risk of continuing sports participation. This is where the majority of COVID cases are coming from,” she said, adding that it is important to discuss this risk with them at appointments. So, when families ask us what we think of in-person learning, I think we should feel fairly confident that the benefit may outweigh the risk.”

Dr. Hobbs and colleagues, and Dr. Kinsella, had no conflicts of interest to report.

[email protected]

SOURCE: MMWR Morb Mortal Wkly Rep. 2020;69:1925-9. doi: 10.15585/mmwr.mm6950e3.

Children and adolescents who receive positive COVID-19 test results are not only more likely to have been in close contact with someone with a confirmed case of the virus but also are less likely to have reported consistent mask use among students and staff inside the school they attended, reported Charlotte V. Hobbs, MD, and colleagues at the University of Mississippi, Jackson.

FluxFactory/E+

Nearly two-thirds reported that exposure came from family members

Of the total study participants observed, 82 (21%) were under 4 years of age; 214 (54%) were female; 217 (55%) were non-Hispanic black, and 145 (37%) were non-Hispanic white. More than half (53%) sought testing because of COVID-19 symptoms. Of those who tested positive, 66% reported having come into close contact with a COVID-19 case, and 64% reported that those contacts were family members, compared with 15% of contacts who were schoolmates and 27% who were child care classmates.

All participants completed in-person school or child care attendance less than 14 days before testing positive for the virus, including 62% of patients testing positive and 68% of those testing negative. The authors noted that school attendance itself was not found to be associated with any positive test results. In fact, parents in 64% of positive cases and 76% of negative cases reported mask wearing among children and staff inside places of learning.

Of those study participants testing positive who did come into close contact with someone with COVID-19, the contacts were more likely to be family members than school or child care classmates. Specifically, they were more likely, in the 2-week period preceding testing, to have attended gatherings with individuals outside their immediate households, including social events and activities with other children. Parents of students testing positive were also less likely to report consistent indoor mask use among their children older than 2 years and school staff members.

School attendance was not found to increase likelihood of testing positive

Attending in-person school or child care during the 2 weeks before the SARS-CoV-2 test was not associated with greater likelihood of testing positive, the study authors noted, adding that the majority of study respondents reported universal mask use inside school and child care facilities, consistent with Mississippi State Department of Health recommended guidelines.

Dr. Hobbs and colleagues reported at least four limitations of the study. They noted that the study participants may not be representative of youth in other geographic regions of the country. They considered the possibility of unmeasured confounding of participant behaviors that may not have been factored into the study. No attempt was made to verify parent claims of mask use at schools and child care programs. Lastly, they acknowledged that “case or control status might be subject to misclassification because of imperfect sensitivity or specificity of PCR-based testing.

As of Dec. 14, 2020, the CDC reported that 10.2% of all COVID-19 cases in the United States were in children and adolescents under the age of 18.

“Continued efforts to prevent transmission at schools and child care programs are important, as are assessments of various types of activities and exposures to identify risk factors for COVID-19 as children engage in classroom and social interactions.” Promoting behaviors to reduce exposures to the virus among youth in the household, the community, schools, and child care programs is important to preventing outbreaks of the virus at schools, the authors cautioned.

In a separate interview with this news organization, Karalyn Kinsella, MD, general pediatrician in a small group private practice in Cheshire, Conn., said, “What this report tells me is that COVID cases are more common when mask use is inconsistent in schools and at home and in schools that don’t properly adhere to CDC guidelines. Overall, so long as social distancing guidelines are followed, schools are pretty safe places for kids during this pandemic.”

This finding is important, since many families are keeping their children out of school over fears of contracting the virus, she added. Some of the consequences these children are suffering include a lack of social connection and structure, which in some cases is leading to worsening anxiety and depression, and for those with disabilities, such as those who receive physical therapy, occupational therapy, speech or have IEPs, they’re not getting the full benefit of the services that they would otherwise receive in person, she observed.

“I don’t think families really understand the risks of getting together with family or friends “in their bubble” or the risk of continuing sports participation. This is where the majority of COVID cases are coming from,” she said, adding that it is important to discuss this risk with them at appointments. So, when families ask us what we think of in-person learning, I think we should feel fairly confident that the benefit may outweigh the risk.”

Dr. Hobbs and colleagues, and Dr. Kinsella, had no conflicts of interest to report.

[email protected]

SOURCE: MMWR Morb Mortal Wkly Rep. 2020;69:1925-9. doi: 10.15585/mmwr.mm6950e3.

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.

In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.

“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.

“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.

The study was published online Jan. 6 in The New England Journal of Medicine.

“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.

Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.

“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.

Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.

Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”

A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.

“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.

However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”

A search for clear answers

Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”

To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.

In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).

The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).

Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.

The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.

“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.

The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.

Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”

Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
 

An inexpensive therapy with global potential?

“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”

Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”

Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”

Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.

“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.

“We are glad it worked,” he said.

The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.

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

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Evidence that a SARS-CoV-2 vaccine is associated with inflammatory reactions in patients with dermal fillers has led the American Society for Dermatologic Surgery to issue a guidance outlining the potential risk and clinical relevance.

The association is not surprising, since other vaccines, including the influenza vaccine, have also been associated with inflammatory reactions in patients with dermal fillers. A warning about inflammatory events from these and other immunologic triggers should be part of routine informed consent, according to Sue Ellen Cox, MD, a coauthor of the guidance and the ASDS president-elect.

“Patients who have had dermal filler should not be discouraged from receiving the vaccine, and those who have received the vaccine should not be discouraged from receiving dermal filler,” Dr. Cox, who practices in Chapel Hill, N.C., said in an interview.

The only available data to assess the risk came from the trial of the Moderna vaccine. Of a total of 15,184 participants who received at least one dose of mRNA-1273, three developed facial or lip swelling that was presumably related to dermal filler. In the placebo group, there were no comparable inflammatory events.

“This is a very small number, but there is no reliable information about the number of patients in either group who had dermal filler, so we do not know the denominator,” Dr. Cox said.

In all three cases, the swelling at the site of dermal filler was observed within 2 days of the vaccination. None were considered a serious adverse event and all resolved. The filler had been administered 2 weeks prior to vaccination in one case, 6 months prior in a second, and time of administration was unknown in the third.

The resolution of the inflammatory reactions associated with the SARS-CoV-2 vaccine is similar to those related to dermal fillers following other immunologic triggers, which not only include other vaccines, but viral or bacterial illnesses and dental procedures. Typically, they are readily controlled with oral corticosteroids, but also typically resolve even in the absence of treatment, according to Dr. Cox.

“The good news is that these will go away,” Dr. Cox said.

The ASDS guidance is meant to alert clinicians and patients to the potential association between inflammatory events and SARS-CoV-2 vaccination in patients with dermal filler, but Dr. Cox said that it will ultimately have very little effect on her own practice. She already employs an informed consent that includes language warning about the potential risk of local reactions to immunological triggers that include vaccines. SARS-CoV-2 vaccination can now be added to examples of potential triggers, but it does not change the importance of informing patients of such triggers, Dr. Cox explained.

Asked if patients should be informed specifically about the association between dermal filler inflammatory reactions and SARS-CoV-2 vaccine, the current ASDS president and first author of the guidance, Mathew Avram, MD, JD, suggested that they should. Although he emphasized that the side effect is clearly rare, he believes it deserves attention.

“We wanted dermatologists and other physicians to be aware of the potential. We focused on the available data but specifically decided not to provide any treatment recommendations at this time,” he said in an interview.

As new data become available, the Soft-Tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other SARS-CoV-2 vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

“Our guidance was based only on the trial data, but there will soon be tens of millions of patients exposed to several different SARS-CoV-2 vaccines. We may learn things we do not know now, and we plan to communicate to our membership and others any new information as events unfold,” said Dr. Avram, who is director of dermatologic surgery, Massachusetts General Hospital, Boston,

Based on her own expertise in the field, Dr. Cox suggested that administration of SARS-CoV-2 vaccine and administration of dermal filler should be separated by at least 2 weeks regardless of which comes first. Her recommendation is not based on controlled data, but she considers this a prudent interval even if it has not been tested in a controlled study.

The full ASDS guidance is scheduled to appear in an upcoming issue of Dermatologic Surgery.

As new data become available, the Soft-tissue Fillers Guideline Task Force of the ASDS, which provided the guidance, will continue to monitor the relationship between SARS-CoV-2 vaccinations and dermal filler reactions, including other types of vaccines and the relative risks for hyaluronic acid and non–hyaluronic acid types of fillers.

This article was updated 1/7/21.

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

Multifocal microvascular injury in the brain and olfactory bulbs is another possible adverse outcome from COVID-19, new research suggests.

Postmortem MRI brain scans of 13 patients who died from COVID-19 showed abnormalities in 10 of the participants. Of these, nine showed punctate hyperintensities, “which represented areas of microvascular injury and fibrinogen leakage,” the investigators reported. Immunostaining also showed a thinning of the basal lamina in five of these patients.

Further analyses showed punctate hypointensities linked to congested blood vessels in 10 patients. These areas were “interpreted as microhemorrhages,” the researchers noted.

There was no evidence of viral infection, including SARS-CoV-2.

“These findings may inform the interpretation of changes observed on [MRI] of punctate hyperintensities and linear hypointensities in patients with COVID-19,” wrote Myoung-Hwa Lee, PhD, a research fellow at the National Institute of Neurological Disorders and Stroke, and colleagues. The findings were published online Dec. 30 in a “correspondence” piece in the New England Journal of Medicine.
 

Interpret with caution

The investigators examined brains from a convenience sample of 19 patients (mean age, 50 years), all of whom died from COVID-19 between March and July 2020.

An 11.7-tesla scanner was used to obtain magnetic resonance microscopy images for 13 of the patients. In order to scan the olfactory bulb, the scanner was set at a resolution of 25 mcm; for the brain, it was set at 100 mcm.

Chromogenic immunostaining was used to assess brain abnormalities found in 10 of the patients. Multiplex fluorescence imaging was also used for some of the patients.

For 18 study participants, a histopathological brain examination was performed. In the patients who also had medical histories available to the researchers, five had mild respiratory syndrome, four had acute respiratory distress syndrome, two had pulmonary embolism, one had delirium, and three had unknown symptoms.

The punctate hyperintensities found on magnetic resonance microscopy were also found on histopathological exam. Collagen IV immunostaining showed a thinning in the basal lamina of endothelial cells in these areas.

In addition to congested blood vessels, punctate hypointensities were linked to areas of fibrinogen leakage – but also to “relatively intact vasculature,” the investigators reported.

“There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion,” they added.

SARS-CoV-2 was also not found in any of the participants. “It is possible that the virus was cleared by the time of death or that viral copy numbers were below the level of detection by our assays,” the researchers noted.

In 13 of the patients, hypertrophic astrocytes, macrophage infiltrates, and perivascular-activated microglia were found. Eight patients showed CD3+ and CD8+ T cells in spaces and lumens next to endothelial cells.

Finally, five patients showed activated microglia next to neurons. This is “suggestive of neuronophagia in the olfactory bulb, substantial nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing,” wrote the investigators.

In summary, vascular pathology was found in 10 cases, perivascular infiltrates were present in 13 cases, acute ischemic hypoxic neurons were present in 6 cases, and changes suggestive of neuronophagia were present in 5 cases.

The researchers noted that, although the study findings may be helpful when interpreting brain changes on MRI scan in this patient population, availability of clinical information for the participants was limited.

Therefore, “no conclusions can be drawn in relation to neurologic features of COVID-19,” they wrote.

The study was funded by NINDS. Dr. Lee and all but one of the other investigators reported no relevant financial relationships; the remaining investigator reported having received grants from NINDS during the conduct of this study.

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

The latest iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Management of Patients With Valvular Heart Disease emphasizes a less invasive approach to the management of patients with valvular heart disease (VHD).

The 2020 ACC/AHA guideline now recommends transcatheter aortic valve implantation over surgical implantation for older individuals, a transcatheter edge-to-edge repair of the mitral valve for patients who are at high risk for surgery, and referral of patients with complicated conditions to designated centers.

The guideline was published online Dec. 17 in Circulation and was simultaneously published in the Journal of the American College of Cardiology. It replaces the 2014 guideline and the 2017 focused update of the guideline, both published in Circulation.

“A huge amount has changed,” Catherine M. Otto, MD, J. Ward Kennedy-Hamilton Endowed Chair in Cardiology and professor of medicine, University of Washington, Seattle, said in an interview.

Dr. Otto cochaired the 2020 Guideline Writing Committee with Rick A. Nishimura, MD, professor of medicine, Mayo Clinic, Rochester, Minn.
 

Expanded use of transcatheter procedures

“One major change is that the transcatheter valve, rather than the surgical valve, is now recommended for a large number of patients, primarily based upon the likelihood that the durability of the transcatheter valve is appropriate for the patient’s life expectancy. So, in most older adults, the transcatheter valve, rather than a surgical valve, would be the treatment for severe aortic stenosis,” she said.

“That’s a huge change,” she added. “Previously, patients had to have surgery to place a prosthetic valve, but now, many patients, particularly older adults, can have a nonsurgical approach when they are only in the hospital overnight, or sometimes even just for the day, to get their valve replaced.”

The 2020 guideline also recommends the transcatheter approach over the surgical approach for mitral valve repair or replacement for individuals who are not candidates for surgery.

“We continue to recommend surgical valve repair for the mitral valve, because we know that there are excellent long-term outcomes with surgical repair,” Dr. Otto said. “But, for people who are at high risk or prohibitive risk for surgery, we now have the option of again using a transcatheter approach or a transcatheter edge-to-edge repair of the valve. It’s a simpler procedure, doesn’t require a big incision, [and] doesn’t require a long hospital stay. Those two procedures are really changing patient management,” she said.
 

A tiered approach to VHD care

A third key change is a recommendation that the U.S. health care system move to a tiered approach, whereby patients with more complex conditions undergo their procedure at comprehensive, high-volume centers, and patients with simpler conditions undergo treatment at primary heart valve centers.

“More complex patients often require multidisciplinary care in order to be managed appropriately. It makes more sense to send them to a center that has the expertise and the teams in place already,” Dr. Otto said.

“Patients needing more straightforward, common procedures could be seen at a primary valve center. Those needing a more complicated procedure would go to the centers with higher volumes. So an important part of what this guideline is trying to do is to get doctors to refer their patients to the appropriate center,” she said.
 

Eagerly anticipated

The 2020 AHA/ACC guideline has been “eagerly anticipated,” Anthony A. Bavry, MD, MPH, UT Southwestern Medical Center, Dallas, Texas, and George J. Arnaoutakis, MD, University of Florida Health, Gainesville, wrote in a perspective article published with the guideline in Circulation.

Dr. Bavry and Dr. Arnaoutakis endorse the guideline recommendation that the U.S. health care system move to a tiered approach.

“To balance excellent outcomes and not compromise access to care, the 2020 Guideline recommends that our health care system move to a tiered approach in the treatment of valve disease, where we recognize level 1 and level 2 Centers,” they wrote.

“The level 1 Comprehensive Heart Valve Center is an important and new introduction to the Guideline,” they noted. “The level 1 Center is defined by the depth and breadth of the procedures offered. While excellent outcomes are possible at lower volume centers, literature supports that higher center and operator volumes of valve procedures are associated with excellent results and low mortality.”

The authors pointed out that level 2 primary valve centers offer many of the same valve procedures as the level 1 centers but are limited by the scope of procedures they can offer.

“For example, specialized procedures such as alternative access TAVR, valve-in-valve TAVR, transcatheter edge-to-edge mitral valve repair, paravalvular leak closure, and percutaneous mitral balloon commissurotomy are recommended to be performed at a level 1 Center,” they wrote.

Transcatheter valve therapies remain “an exciting and dynamic field which offers patients a less invasive treatment option,” Dr. Bavry and Dr. Arnaoutakis concluded. They also cautioned that the pros and cons of the newer, less invasive therapies need to be weighed against the benefits of surgical procedures that have been studied and refined for more than 50 years.

Patients with VHD have many choices and will require help making informed decisions about such things as a mechanical valve vs. a bioprosthetic valve or undergoing a traditional surgical procedure vs. a catheter-based approach. “Other patients, at the extremes of age or risk status, will lean more clearly to one direction or another,” Dr. Bavry and Dr. Arnaoutakis add.

“Overall, the 2020 Guideline is a comprehensive document that should provide a useful framework for the Heart Valve Team,” they concluded.

The authors have disclosed no relevant financial relationships.

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

The latest iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Management of Patients With Valvular Heart Disease emphasizes a less invasive approach to the management of patients with valvular heart disease (VHD).

The 2020 ACC/AHA guideline now recommends transcatheter aortic valve implantation over surgical implantation for older individuals, a transcatheter edge-to-edge repair of the mitral valve for patients who are at high risk for surgery, and referral of patients with complicated conditions to designated centers.

The guideline was published online Dec. 17 in Circulation and was simultaneously published in the Journal of the American College of Cardiology. It replaces the 2014 guideline and the 2017 focused update of the guideline, both published in Circulation.

“A huge amount has changed,” Catherine M. Otto, MD, J. Ward Kennedy-Hamilton Endowed Chair in Cardiology and professor of medicine, University of Washington, Seattle, said in an interview.

Dr. Otto cochaired the 2020 Guideline Writing Committee with Rick A. Nishimura, MD, professor of medicine, Mayo Clinic, Rochester, Minn.
 

Expanded use of transcatheter procedures

“One major change is that the transcatheter valve, rather than the surgical valve, is now recommended for a large number of patients, primarily based upon the likelihood that the durability of the transcatheter valve is appropriate for the patient’s life expectancy. So, in most older adults, the transcatheter valve, rather than a surgical valve, would be the treatment for severe aortic stenosis,” she said.

“That’s a huge change,” she added. “Previously, patients had to have surgery to place a prosthetic valve, but now, many patients, particularly older adults, can have a nonsurgical approach when they are only in the hospital overnight, or sometimes even just for the day, to get their valve replaced.”

The 2020 guideline also recommends the transcatheter approach over the surgical approach for mitral valve repair or replacement for individuals who are not candidates for surgery.

“We continue to recommend surgical valve repair for the mitral valve, because we know that there are excellent long-term outcomes with surgical repair,” Dr. Otto said. “But, for people who are at high risk or prohibitive risk for surgery, we now have the option of again using a transcatheter approach or a transcatheter edge-to-edge repair of the valve. It’s a simpler procedure, doesn’t require a big incision, [and] doesn’t require a long hospital stay. Those two procedures are really changing patient management,” she said.
 

A tiered approach to VHD care

A third key change is a recommendation that the U.S. health care system move to a tiered approach, whereby patients with more complex conditions undergo their procedure at comprehensive, high-volume centers, and patients with simpler conditions undergo treatment at primary heart valve centers.

“More complex patients often require multidisciplinary care in order to be managed appropriately. It makes more sense to send them to a center that has the expertise and the teams in place already,” Dr. Otto said.

“Patients needing more straightforward, common procedures could be seen at a primary valve center. Those needing a more complicated procedure would go to the centers with higher volumes. So an important part of what this guideline is trying to do is to get doctors to refer their patients to the appropriate center,” she said.
 

Eagerly anticipated

The 2020 AHA/ACC guideline has been “eagerly anticipated,” Anthony A. Bavry, MD, MPH, UT Southwestern Medical Center, Dallas, Texas, and George J. Arnaoutakis, MD, University of Florida Health, Gainesville, wrote in a perspective article published with the guideline in Circulation.

Dr. Bavry and Dr. Arnaoutakis endorse the guideline recommendation that the U.S. health care system move to a tiered approach.

“To balance excellent outcomes and not compromise access to care, the 2020 Guideline recommends that our health care system move to a tiered approach in the treatment of valve disease, where we recognize level 1 and level 2 Centers,” they wrote.

“The level 1 Comprehensive Heart Valve Center is an important and new introduction to the Guideline,” they noted. “The level 1 Center is defined by the depth and breadth of the procedures offered. While excellent outcomes are possible at lower volume centers, literature supports that higher center and operator volumes of valve procedures are associated with excellent results and low mortality.”

The authors pointed out that level 2 primary valve centers offer many of the same valve procedures as the level 1 centers but are limited by the scope of procedures they can offer.

“For example, specialized procedures such as alternative access TAVR, valve-in-valve TAVR, transcatheter edge-to-edge mitral valve repair, paravalvular leak closure, and percutaneous mitral balloon commissurotomy are recommended to be performed at a level 1 Center,” they wrote.

Transcatheter valve therapies remain “an exciting and dynamic field which offers patients a less invasive treatment option,” Dr. Bavry and Dr. Arnaoutakis concluded. They also cautioned that the pros and cons of the newer, less invasive therapies need to be weighed against the benefits of surgical procedures that have been studied and refined for more than 50 years.

Patients with VHD have many choices and will require help making informed decisions about such things as a mechanical valve vs. a bioprosthetic valve or undergoing a traditional surgical procedure vs. a catheter-based approach. “Other patients, at the extremes of age or risk status, will lean more clearly to one direction or another,” Dr. Bavry and Dr. Arnaoutakis add.

“Overall, the 2020 Guideline is a comprehensive document that should provide a useful framework for the Heart Valve Team,” they concluded.

The authors have disclosed no relevant financial relationships.

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

The latest iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Management of Patients With Valvular Heart Disease emphasizes a less invasive approach to the management of patients with valvular heart disease (VHD).

The 2020 ACC/AHA guideline now recommends transcatheter aortic valve implantation over surgical implantation for older individuals, a transcatheter edge-to-edge repair of the mitral valve for patients who are at high risk for surgery, and referral of patients with complicated conditions to designated centers.

The guideline was published online Dec. 17 in Circulation and was simultaneously published in the Journal of the American College of Cardiology. It replaces the 2014 guideline and the 2017 focused update of the guideline, both published in Circulation.

“A huge amount has changed,” Catherine M. Otto, MD, J. Ward Kennedy-Hamilton Endowed Chair in Cardiology and professor of medicine, University of Washington, Seattle, said in an interview.

Dr. Otto cochaired the 2020 Guideline Writing Committee with Rick A. Nishimura, MD, professor of medicine, Mayo Clinic, Rochester, Minn.
 

Expanded use of transcatheter procedures

“One major change is that the transcatheter valve, rather than the surgical valve, is now recommended for a large number of patients, primarily based upon the likelihood that the durability of the transcatheter valve is appropriate for the patient’s life expectancy. So, in most older adults, the transcatheter valve, rather than a surgical valve, would be the treatment for severe aortic stenosis,” she said.

“That’s a huge change,” she added. “Previously, patients had to have surgery to place a prosthetic valve, but now, many patients, particularly older adults, can have a nonsurgical approach when they are only in the hospital overnight, or sometimes even just for the day, to get their valve replaced.”

The 2020 guideline also recommends the transcatheter approach over the surgical approach for mitral valve repair or replacement for individuals who are not candidates for surgery.

“We continue to recommend surgical valve repair for the mitral valve, because we know that there are excellent long-term outcomes with surgical repair,” Dr. Otto said. “But, for people who are at high risk or prohibitive risk for surgery, we now have the option of again using a transcatheter approach or a transcatheter edge-to-edge repair of the valve. It’s a simpler procedure, doesn’t require a big incision, [and] doesn’t require a long hospital stay. Those two procedures are really changing patient management,” she said.
 

A tiered approach to VHD care

A third key change is a recommendation that the U.S. health care system move to a tiered approach, whereby patients with more complex conditions undergo their procedure at comprehensive, high-volume centers, and patients with simpler conditions undergo treatment at primary heart valve centers.

“More complex patients often require multidisciplinary care in order to be managed appropriately. It makes more sense to send them to a center that has the expertise and the teams in place already,” Dr. Otto said.

“Patients needing more straightforward, common procedures could be seen at a primary valve center. Those needing a more complicated procedure would go to the centers with higher volumes. So an important part of what this guideline is trying to do is to get doctors to refer their patients to the appropriate center,” she said.
 

Eagerly anticipated

The 2020 AHA/ACC guideline has been “eagerly anticipated,” Anthony A. Bavry, MD, MPH, UT Southwestern Medical Center, Dallas, Texas, and George J. Arnaoutakis, MD, University of Florida Health, Gainesville, wrote in a perspective article published with the guideline in Circulation.

Dr. Bavry and Dr. Arnaoutakis endorse the guideline recommendation that the U.S. health care system move to a tiered approach.

“To balance excellent outcomes and not compromise access to care, the 2020 Guideline recommends that our health care system move to a tiered approach in the treatment of valve disease, where we recognize level 1 and level 2 Centers,” they wrote.

“The level 1 Comprehensive Heart Valve Center is an important and new introduction to the Guideline,” they noted. “The level 1 Center is defined by the depth and breadth of the procedures offered. While excellent outcomes are possible at lower volume centers, literature supports that higher center and operator volumes of valve procedures are associated with excellent results and low mortality.”

The authors pointed out that level 2 primary valve centers offer many of the same valve procedures as the level 1 centers but are limited by the scope of procedures they can offer.

“For example, specialized procedures such as alternative access TAVR, valve-in-valve TAVR, transcatheter edge-to-edge mitral valve repair, paravalvular leak closure, and percutaneous mitral balloon commissurotomy are recommended to be performed at a level 1 Center,” they wrote.

Transcatheter valve therapies remain “an exciting and dynamic field which offers patients a less invasive treatment option,” Dr. Bavry and Dr. Arnaoutakis concluded. They also cautioned that the pros and cons of the newer, less invasive therapies need to be weighed against the benefits of surgical procedures that have been studied and refined for more than 50 years.

Patients with VHD have many choices and will require help making informed decisions about such things as a mechanical valve vs. a bioprosthetic valve or undergoing a traditional surgical procedure vs. a catheter-based approach. “Other patients, at the extremes of age or risk status, will lean more clearly to one direction or another,” Dr. Bavry and Dr. Arnaoutakis add.

“Overall, the 2020 Guideline is a comprehensive document that should provide a useful framework for the Heart Valve Team,” they concluded.

The authors have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

A proposal to delay administration of the second dose of COVID-19 vaccines – suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines – is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco, and Ashish Jha, MD, MPH, at Brown University in Providence, R.I., wrote in an opinion piece in The Washington Post Jan. 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cited a study in the New England Journal of Medicine that suggests 80%-90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing – that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said in an interview.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Dr. Bottazzi said. “I appreciate the urgency and the anxiety ... but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the United States, the Food and Drug Administration would have to approve any dosing change.
 

Agreeing to disagree

Dr. Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on Jan. 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an interview. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Dr. Shen said. “We don’t have data that one dose is going to have lasting protection.” 
 

Does new variant change equation?

Dr. Wachter and Dr. Jha, in their editorial, cited a quote from former boxing champion Mike Tyson: “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant – I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on Twitter.

 

Vaccine and public resistance raised

“I agree with the problem but not with the proposed solution, which is guesswork not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York responded to Dr. Wachter and Dr. Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Dr. Shen and Dr. Bottazzi have disclosed no relevant financial relationships.

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

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

SARS-CoV-2 can invade the brain and directly act on brain cells, causing neuroinflammation, new animal research suggests. Investigators injected spike 1 (S1), which is found on the tufts of the “red spikes” of the virus, into mice and found that it crossed the blood-brain barrier (BBB) and was taken up not only by brain regions and the brain space but also by other organs – specifically, the lungs, spleen, liver, and kidneys.

“We found that the S1 protein, which is the protein COVID-19 uses to ‘grab onto’ cells, crosses the BBB and is a good model of what the virus does when it enters the brain,” lead author William A. Banks, MD, professor of medicine, University of Washington, Seattle, said in an interview.

“When proteins such as the S1 protein become detached from the virus, they can enter the brain and cause mayhem, causing the brain to release cytokines, which, in turn, cause inflammation and subsequent neurotoxicity,” said Dr. Banks, associate chief of staff and a researcher at the Puget Sound Veterans Affairs Healthcare System.

The study was published online in Nature Neuroscience.
 

Neurologic symptoms

COVID-19 is associated with a variety of central nervous system symptoms, including the loss of taste and smell, headaches, confusion, stroke, and cerebral hemorrhage, the investigators noted.

Dr. Banks explained that SARS-CoV-2 may enter the brain by crossing the BBB, acting directly on the brain centers responsible for other body functions. The respiratory symptoms of COVID-19 may therefore result partly from the invasion of the areas of the brain responsible for respiratory functions, not only from the virus’ action at the site of the lungs.

The researchers set out to assess whether a particular viral protein – S1, which is a subunit of the viral spike protein – could cross the BBB or enter other organs when injected into mice. They found that, when intravenously injected S1 (I-S1) was cleared from the blood, tissues in multiple organs, including the lung, spleen, kidney, and liver, took it up.

Notably, uptake of I-S1 was higher in the liver, “suggesting that this protein is cleared from the blood predominantly by the liver,” Dr. Banks said. In addition, uptake by the lungs is “important, because that’s where many of the effects of the virus are,” he added.

The researchers found that I-S1 in the brains of the mice was “mostly degraded” 30 minutes following injection. “This indicates that I-S1 enters the BBB intact but is eventually degraded in the brain,” they wrote.

Moreover, by 30 minutes, more than half of the I-S1 proteins had crossed the capillary wall and had fully entered into the brain parenchymal and interstitial fluid spaces, as well as other regions.
 

More severe outcomes in men

The researchers then induced an inflammatory state in the mice through injection of lipopolysaccharide (LPS) and found that inflammation increased I-S1 uptake in both the brain and the lung (where uptake was increased by 101%). “These results show that inflammation could increase S1 toxicity for lung tissue by increasing its uptake,” the authors suggested. Moreover, inflammation also increased the entry of I-S1 into the brain, “likely due to BBB disruption.”

In human beings, male sex and APOE4 genotype are risk factors for both contracting COVID-19 and having a poor outcome, the authors noted. As a result, they examined I-S1 uptake in male and female mice that expressed human APOE3 or APOE4 (induced by a mouse ApoE promoter).

Multiple-comparison tests showed that among male mice that expressed human APOE3, the “fastest I-S1 uptake” was in the olfactory bulb, liver, and kidney. Female mice displayed increased APOE3 uptake in the spleen.

“This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes,” coauthor Jacob Raber, PhD, professor, departments of behavioral neuroscience, neurology, and radiation medicine, Oregon Health & Science University, Portland, said in a press release.

In addition to intravenous I-S1 injection, the researchers also investigated the effects of intranasal administration. They found that, although it also entered the brain, it did so at levels roughly 10 times lower than those induced by intravenous administration.
 

“Frightening tricks”

Dr. Banks said his laboratory has studied the BBB in conditions such as Alzheimer’s disease, obesity, diabetes, and HIV. “Our experience with viruses is that they do an incredible number of things and have a frightening number of tricks,” he said. In this case, “the virus is probably causing inflammation by releasing cytokines elsewhere in the body that get into the brain through the BBB.” Conversely, “the virus itself may enter the brain by crossing the BBB and directly cause brain cells to release their own cytokines,” he added.

An additional finding of the study is that, whatever the S1 protein does in the brain is a model for what the entire virus itself does, because these proteins often bring the viruses along with them, he added.

Dr. Banks said the clinical implications of the findings are that antibodies from those who have already had COVID-19 could potentially be directed against S1. Similarly, he added, so can COVID-19 vaccines, which induce production of S1.

“When an antibody locks onto something, it prevents it from crossing the BBB,” Dr. Banks noted.
 

Confirmatory findings

Commenting on the study, Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases and professor and chair of the department of pharmacology and experimental neuroscience, University of Nebraska, Omaha, said the study is confirmatory.

“What this paper highlights, and we have known for a long time, is that COVID-19 is a systemic, not only a respiratory, disease involving many organs and tissues and can yield not only pulmonary problems but also a whole host of cardiac, brain, and kidney problems,” he said.

“So the fact that these proteins are getting in [the brain] and are able to induce a reaction in the brain itself, and this is part of the complex progressive nature of COVID-19, is an important finding,” added Dr. Gendelman, director of the center for neurodegenerative disorders at the university. He was not involved with the study.

The study was supported by the Veterans Affairs Puget Sound Healthcare System and by grants from the National Institutes of Health. The authors and Dr. Gendelman have disclosed no relevant financial relationships.

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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

The United States started 2021 they way it ended 2020: Setting new records amidst the coronavirus pandemic.

Courtesy NIAID-RML

The country passed the 20 million mark for coronavirus cases on Friday, setting the mark sometime around noon, according to Johns Hopkins University’s COVID-19 tracker. The total is nearly twice as many as the next worst country – India, which has 10.28 million cases.

Along with the case count, more than 346,000 Americans have now died of COVID-19, the disease caused by the coronavirus. That is 77% more fatalities than Brazil, which ranks second globally with 194,949 deaths.

More than 125,370 coronavirus patients were hospitalized on Thursday, the fourth record-setting day in a row, according to the COVID Tracking Project.

Going by official tallies, it took 292 days for the United States to reach its first 10 million cases, and just 54 more days to double it, CNN reported.

Meanwhile, 12.41 million doses of COVID-19 vaccines have been distributed in the United States as of Wednesday, according to the Centers for Disease Control and Prevention. Yet only 2.8 million people have received the first of a two-shot regimen.

The slower-than-hoped-for rollout of the Pfizer and Moderna vaccines comes as a new variant of the coronavirus has emerged in a third state. Florida officials announced a confirmed case of the new variant – believed to have originated in the United Kingdom – in Martin County in southeast Florida.

The state health department said on Twitter that the patient is a man in his 20s with no history of travel. The department said it is working with the CDC to investigate.

The variant has also been confirmed in cases in Colorado and California. It is believed to be more contagious. The BBC reported that the new variant increases the reproduction, or “R number,” by 0.4 and 0.7. The UK’s most recent R number has been estimated at 1.1-1.3, meaning anyone who has the coronavirus could be assumed to spread it to up to 1.3 people.

The R number needs to be below 1.0 for the spread of the virus to fall.

“There is a huge difference in how easily the variant virus spreads,” Professor Axel Gandy of London’s Imperial College told BBC News. “This is the most serious change in the virus since the epidemic began.”

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