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Ticking all the right boxes for same-day discharge PCI
The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).
“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.
Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.
The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.
When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.
The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.
Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.
“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”
The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.
“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”
Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.
Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.
“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”
Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.
“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”
Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.
That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”
“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.
The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.
Dr. Rao and Dr. Hess report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).
“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.
Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.
The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.
When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.
The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.
Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.
“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”
The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.
“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”
Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.
Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.
“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”
Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.
“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”
Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.
That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”
“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.
The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.
Dr. Rao and Dr. Hess report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
The American College of Cardiology has released a new expert consensus decision pathway to provide practical guidance on same-day discharge after percutaneous coronary intervention (PCI).
“There’s been a lot of interest in people wanting to start these programs, so we thought this is an ideal topic for a consensus pathway that will help programs that want to implement these things – give them kind of a road map for how to do that,” writing committee chair Sunil Rao, MD, Duke University Medical Center, Durham, N.C., said.
Although the document reviews the evidence supporting same-day discharge much like a guideline, the focus is on implementation, he said in an interview. It features a checklist of patient- and systems-specific considerations along with key definitions and a series of clinical scenarios showing the rationale for same-day discharge or overnight monitoring.
The checklist can be used for anyone presenting for an elective PCI or for ad hoc cases that flow directly from the diagnostic cath lab and make up about 80% of procedures. It is not applicable for those presenting with ST-elevation myocardial infarction (STEMI) or non-STEMI, but can be used for staged procedures performed after their index PCI, according to the report, published online Jan. 7 in the Journal of the American College of Cardiology.
When establishing a new same-day discharge program, the basic approach can be distilled down to the “three Ps”– the patient, the procedure, and the program – Dr. Rao explained. The patient has to be the right patient, be willing to go home that night, and have some kind of support structure at home in case they run into trouble. The procedure itself should be without complications and the recovery unremarkable, with a stable access site and a return to baseline mental status and ambulation. Finally, “this all has to take place in the context of a program with buy-in from the different stakeholders,” he said.
The report points out that the need for administrative buy-in “should not be underestimated” and recommends physician-champions meet with staff administrators to present the data on PCI utility and safety and to communicate the need for staff to complete the checklist.
Implementing the checklist also requires buy-in from nurses and other team members who may be tasked with educating patients on issues like access site complications and ensuring they receive relevant discharge information, a loading dose of a P2Y12 inhibitor, and appropriate prescriptions.
“If you’re only going to observe the patient for 6 hours, you’ve got to make sure that they’re on all the secondary prevention medications and the referral to cardiac rehabilitation takes place,” Dr. Rao said. “So I think that, in a funny way, the implementation of same-day discharge allows us to actually focus a little bit more on these kinds of postprocedure aspects that I think we were taking for granted a little bit when patients were being observed overnight.”
The checklist is detailed but was designed so it can be tailored to the needs of individual institutions, writing committee member Connie N. Hess, MD, MHS, University of Colorado at Denver, Aurora, pointed out.
“At every level there is a lot of variance in institutional resources or even a patient’s resources,” she said. “So we didn’t want to seem too prescriptive.”
Some institutions, for example, may feel strongly that accessibility to a caregiver means someone staying in the house who can monitor the patient’s access site and call 911 if need be, whereas others may define it as having a neighbor who’s easy to reach by phone, Dr. Hess noted in an interview.
Exactly when the last patient can be eligible for same-day discharge may also vary between urban and rural settings where patients may drive hours for their care. The built-in flexibility also allows institutions to incorporate their own preexisting documents into the checklist.
“I don’t think the hospital buy-in is necessarily the hard part because there is a clear monetary benefit as long as you can show that it’s done safely and you’re not harming patients, which I think has been done,” Dr. Hess said. “I think then the next level down, you have the provider buy-in and that may be where there might be a little bit more work depending on the preexisting culture.”
Part of the hesitancy may reflect a generational gap, whereby younger interventionalists who trained in programs with same-day discharge may be more willing to support the checklist.
“This actually parallels radial artery access where data exists on its benefits but it’s not used,” Dr. Hess said. “And I think a lot of this has to do with provider comfort levels with sending patients home and just not necessarily knowing how to implement a program at their institution.”
Both Dr. Rao and Dr. Hess pointed out that uptake of same-day discharge PCI is low in the United States, compared with other part of the world, including the United Kingdom, with estimates at about 16%-20% of PCIs.
That said, the timing of the new expert consensus document is “fortuitous,” Dr. Rao noted. Since work on the document began 2 years ago, the Centers for Medicare & Medicaid Services’ greenlit reimbursement for PCI performed in an ambulatory surgical center and the pandemic walloped U.S. hospitals. “I think those two things really do highlight the importance of a document like this.”
“A potential advantage of the same-day discharge program is that you won’t be exposing patients to the hospital setting where COVID is a problem, and you’ll keep your beds open for the COVID patients that really do need it,” he said.
The ability to go home without an overnight stay may also encourage some patients to seek care. “Patients with cardiovascular disease really need to understand that you may be stable at one point but then obviously can become unstable, and we don’t want people to stay away from the hospital because they are worried about being admitted,” Dr. Rao said.
Dr. Rao and Dr. Hess report no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Over half of COVID-19 transmission may occur via asymptomatic people
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.
The Centers for Disease Control and Prevention study, published online Jan. 7 in JAMA Network Open, concludes that for optimal control, protective measures such as masking and social distancing should be supplemented with strategic testing of potentially exposed but asymptomatic individuals .
“In the absence of effective and widespread use of therapeutics or vaccines that can shorten or eliminate infectivity, successful control of SARS-CoV-2 cannot rely solely on identifying and isolating symptomatic cases; even if implemented effectively, this strategy would be insufficient,” CDC biologist Michael J. Johansson, PhD, and colleagues warn. “Multiple measures that effectively address transmission risk in the absence of symptoms are imperative to control SARS-CoV-2.”
According to the authors, the effectiveness of some current transmission prevention efforts has been disputed and subject to mixed messaging. Therefore, they decided to model the proportion of COVID-19 infections that are likely the result of individuals who show no symptoms and may be unknowingly infecting others.
“Unfortunately, there continues to be some skepticism about the value of community-wide mitigation efforts for preventing transmission such as masking, distancing, and hand hygiene, particularly for people without symptoms,” corresponding author Jay C. Butler, MD, said in an interview. “So we wanted to have a base assumption about how much transmission occurs from asymptomatic people to underscore the importance of mitigation measures and of creating immunity through vaccine delivery.”
Such a yardstick is especially germane in the context of the new, more transmissible variant. “It really puts [things] in a bigger box and underscores, boldfaces, and italicizes the need to change people’s behaviors and the importance of mitigation,” Dr. Butler said. It also highlights the advisability of targeted strategic testing in congregate settings, schools, and universities, which is already underway.
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.
The Centers for Disease Control and Prevention study, published online Jan. 7 in JAMA Network Open, concludes that for optimal control, protective measures such as masking and social distancing should be supplemented with strategic testing of potentially exposed but asymptomatic individuals .
“In the absence of effective and widespread use of therapeutics or vaccines that can shorten or eliminate infectivity, successful control of SARS-CoV-2 cannot rely solely on identifying and isolating symptomatic cases; even if implemented effectively, this strategy would be insufficient,” CDC biologist Michael J. Johansson, PhD, and colleagues warn. “Multiple measures that effectively address transmission risk in the absence of symptoms are imperative to control SARS-CoV-2.”
According to the authors, the effectiveness of some current transmission prevention efforts has been disputed and subject to mixed messaging. Therefore, they decided to model the proportion of COVID-19 infections that are likely the result of individuals who show no symptoms and may be unknowingly infecting others.
“Unfortunately, there continues to be some skepticism about the value of community-wide mitigation efforts for preventing transmission such as masking, distancing, and hand hygiene, particularly for people without symptoms,” corresponding author Jay C. Butler, MD, said in an interview. “So we wanted to have a base assumption about how much transmission occurs from asymptomatic people to underscore the importance of mitigation measures and of creating immunity through vaccine delivery.”
Such a yardstick is especially germane in the context of the new, more transmissible variant. “It really puts [things] in a bigger box and underscores, boldfaces, and italicizes the need to change people’s behaviors and the importance of mitigation,” Dr. Butler said. It also highlights the advisability of targeted strategic testing in congregate settings, schools, and universities, which is already underway.
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.
The Centers for Disease Control and Prevention study, published online Jan. 7 in JAMA Network Open, concludes that for optimal control, protective measures such as masking and social distancing should be supplemented with strategic testing of potentially exposed but asymptomatic individuals .
“In the absence of effective and widespread use of therapeutics or vaccines that can shorten or eliminate infectivity, successful control of SARS-CoV-2 cannot rely solely on identifying and isolating symptomatic cases; even if implemented effectively, this strategy would be insufficient,” CDC biologist Michael J. Johansson, PhD, and colleagues warn. “Multiple measures that effectively address transmission risk in the absence of symptoms are imperative to control SARS-CoV-2.”
According to the authors, the effectiveness of some current transmission prevention efforts has been disputed and subject to mixed messaging. Therefore, they decided to model the proportion of COVID-19 infections that are likely the result of individuals who show no symptoms and may be unknowingly infecting others.
“Unfortunately, there continues to be some skepticism about the value of community-wide mitigation efforts for preventing transmission such as masking, distancing, and hand hygiene, particularly for people without symptoms,” corresponding author Jay C. Butler, MD, said in an interview. “So we wanted to have a base assumption about how much transmission occurs from asymptomatic people to underscore the importance of mitigation measures and of creating immunity through vaccine delivery.”
Such a yardstick is especially germane in the context of the new, more transmissible variant. “It really puts [things] in a bigger box and underscores, boldfaces, and italicizes the need to change people’s behaviors and the importance of mitigation,” Dr. Butler said. It also highlights the advisability of targeted strategic testing in congregate settings, schools, and universities, which is already underway.
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.
Anaphylaxis cases after COVID-19 vaccine rising but still rare: CDC
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.
IDSA panel updates guidelines on COVID molecular diagnostic tests
Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.
In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.
The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
Throat swab alone less effective
Using a throat swab alone was less effective and missed more cases than the other methods, she said.
The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.
A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.
She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.
Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.
Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
Rapid testing vs. standard
Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.
The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.
The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted.
Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”
But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.
Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.
And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.
“You will miss a certain percentage of people using this rapid isothermal test,” she said.
However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”
On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”
The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.
Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
Testing the immunocompromised
Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.
Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.
But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
Home testing
The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.
Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.
“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.
The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.
Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”
Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.
In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.
The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
Throat swab alone less effective
Using a throat swab alone was less effective and missed more cases than the other methods, she said.
The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.
A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.
She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.
Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.
Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
Rapid testing vs. standard
Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.
The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.
The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted.
Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”
But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.
Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.
And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.
“You will miss a certain percentage of people using this rapid isothermal test,” she said.
However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”
On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”
The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.
Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
Testing the immunocompromised
Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.
Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.
But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
Home testing
The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.
Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.
“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.
The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.
Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”
Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Saliva spit tests stack up well against the gold standard for molecular COVID-19 tests – the back-of-the-nose deep swab – without the discomfort and induced coughing or sneezing of the test taker, updated guidelines indicate.
In a press briefing on Jan. 6, the Infectious Diseases Society of America explained the findings of an expert panel that reviewed the literature since the IDSA released its first guidelines in May.
The panel found that saliva tests were especially effective if the test included instructions to cough or clear the throat before spitting into the tube, said panel chair Kimberly E. Hanson, MD, MHS, of University of Utah Health, Salt Lake City.
Throat swab alone less effective
Using a throat swab alone was less effective and missed more cases than the other methods, she said.
The IDSA has updated its recommendation: A saliva test or swabs from either the middle or front of the nose front are preferred to a throat swab alone.
A combination of saliva and swabs from the front and middle of the nose and throat together “looked pretty much equivalent” to the gold-standard deep swab, the panel found.
She acknowledged, however, that multiple swabs exacerbate already challenging supply issues.
Saliva samples do come with challenges, Dr. Hanson noted. A laboratory must validate that its systems can handle the stickier material. And asking a patient to cough necessitates more personal protective equipment for the health care professional.
Each center will have to tailor the specimen type it chooses, based on what resources it has available and the setting – whether in a hospital or a drive-through operation, for instance, she said.
Rapid testing vs. standard
Panel member Angela M. Caliendo, MD, PhD, of Brown University, Providence, R.I., said the panel preferred rapid polymerase chain reaction tests and standard, laboratory-based PCR tests over a rapid isothermal test.
The panel defined rapid tests as those for which results are available within an hour after a test provider has the specimen in hand. They excluded home tests for this category.
The only rapid isothermal test that had enough data on which to issue a recommendation was the ID NOW test (Abbott Labs), she noted.
Rapid PCR tests performed just as well as the standard laboratory-based tests, she said, with a high sensitivity of “97% on average and a very high specificity.”
But the rapid isothermal test had an average sensitivity of only about 80%, compared with the lab-based PCR test, Dr. Caliendo said, yielding a substantial number of false-negative results.
Testing centers will have to weigh the considerable advantages of having results in 15 minutes with a rapid isothermal test and being able to educate positive patients about immediate isolation against the potential for false negatives, which could send positive patients home thinking they don’t have the virus – and thus potentially spreading the disease.
And if a clinician gets a negative result with the rapid isothermal test, but has a strong suspicion the person has COVID or lives in an area with high prevalence, a backup test with a rapid PCR or laboratory-based test should be administered.
“You will miss a certain percentage of people using this rapid isothermal test,” she said.
However, Dr. Caliendo said, if the only available option is the isothermal test, “you should definitely use it because it’s certainly better than not testing at all.”
On a positive note, she said, all the varieties of tests have high specificity, so “you’re not going to see a lot of false-positive results.”
The guidelines back in May didn’t make recommendations on rapid tests, she said, because there weren’t enough data in the literature.
Dr. Caliendo noted that most of the available data were for symptomatic patients, but there are some data that show the amount of virus in the respiratory tract is similar for people with and without symptoms. The panel, therefore, expects that the performance of the various assays would be similar whether or not a person had symptoms.
Testing the immunocompromised
Dr. Hanson said the original recommendation in May was to do molecular testing for asymptomatic people who were awaiting a transplant or were waiting to start immunosuppressive therapy for cancer or an autoimmune disease. Now the current guidelines “make no recommendation for or against screening” in those cases.
Dr. Hanson added that the panel feels that patients awaiting bone marrow and solid organ transplants should have the testing because of the high risks that will result if patients have contracted the virus.
But for those with cancer or an autoimmune disease, the panel decided to leave it up to each physician to assess individual risk and determine whether the patient should be tested.
Home testing
The IDSA guidelines didn’t weigh in on home testing because the products are so new and studies so far have included fewer than 200 patients. But Dr. Caliendo said they clearly perform better earlier in the disease phase – the first 5-7 days – when the amount of the virus is higher.
Dr. Hanson and Dr. Caliendo also fielded a question about what the new virus variant, first discovered in the United Kingdom and now spreading to other countries (including the United States) means for diagnostic testing.
“So far we think with the majority of tests that are [emergency use] authorized, it doesn’t look like this new variant should really affect test performance,” Dr. Hanson said.
The variant has differences in the spike gene, and many of the current tests detect and identify SARS-CoV-2 without the spike gene so they wouldn’t be affected, she added.
Dr. Caliendo agreed: “I think the vast majority of our tests should be in good shape.”
Dr. Hanson and Dr. Caliendo disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Guidance issued on COVID vaccine use in patients with dermal fillers
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.
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.
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.
Ultraprocessed food again linked to increased CVD, death
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.
In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.
High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.
The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.
Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.
A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.
As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.
Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
Where’s the food?
There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.
Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.
The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.
Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.
UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.
Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.
The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).
High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.
In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.
During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
The more UPF, the higher the risk for CVD, death
The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.
Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).
High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.
Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.
Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.
The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.
“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.
“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.
“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.
The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Microvascular injury of brain, olfactory bulb seen in 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.
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.
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.
ACC/AHA valvular heart disease update backs less-invasive approach
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.
Experts debate wisdom of delaying second COVID-19 vaccine dose
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.
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.
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.
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.
New evidence shows that COVID-19 invades the brain
, 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.
, 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.
, 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.
FROM NATURE NEUROSCIENCE