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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.

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

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

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

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

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

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

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

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

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

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

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

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

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

A search for clear answers

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

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

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

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

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

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

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

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

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

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

An inexpensive therapy with global potential?

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

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

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

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

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

“We are glad it worked,” he said.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A search for clear answers

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

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

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

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

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

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

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

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

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

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

An inexpensive therapy with global potential?

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

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

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

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

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

“We are glad it worked,” he said.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A search for clear answers

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

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

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

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

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

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

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

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

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

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

An inexpensive therapy with global potential?

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

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

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

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

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

“We are glad it worked,” he said.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article was updated 1/7/21.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article was updated 1/7/21.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article was updated 1/7/21.

The proportion of all COVID-19 cases occurring in children, which has been rising gradually throughout the pandemic, did not rise during the week ending Dec. 31, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children’s share of the cumulative COVID-19 burden remained at 12.4% for a second consecutive week, the AAP and CHA said in their weekly report. The last full week of 2020 also marked the second consecutive drop in new cases, although that may be holiday related.

There were almost 128,000 new cases of COVID-19 reported in children for the week, down from 179,000 cases the week before (Dec. 24) and down from the pandemic high of 182,000 reported 2 weeks earlier (Dec.17), based on data from 49 state health departments (excluding New York), along with the District of Columbia, New York City, Puerto Rico, and Guam.

Children’s proportion of new cases for the week, 12.6%, is at its lowest point since early October after dropping for the second week in a row. The cumulative rate of COVID-19 infection, however, is now 2,828 cases per 100,000 children, up from 2,658 the previous week, the AAP and CHA said.

State-level metrics show that North Dakota has the highest cumulative rate at 7,851 per 100,000 children and Hawaii the lowest at 828. Wyoming’s cumulative proportion of child cases, 20.3%, is the highest in the country, while Florida, which uses an age range of 0-14 years for children, is the lowest at 7.1%. California’s total of 268,000 cases is almost double the number of second-place Illinois (138,000), the AAP/CHA data show.

Cumulative child deaths from COVID-19 are up to 179 in the jurisdictions reporting such data (43 states and New York City). That represents just 0.6% of all coronavirus-related deaths and has changed little over the last several months – never rising higher than 0.7% or dropping below 0.6% since early July, according to the report.

rfranki@mdedge.com

The proportion of all COVID-19 cases occurring in children, which has been rising gradually throughout the pandemic, did not rise during the week ending Dec. 31, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children’s share of the cumulative COVID-19 burden remained at 12.4% for a second consecutive week, the AAP and CHA said in their weekly report. The last full week of 2020 also marked the second consecutive drop in new cases, although that may be holiday related.

There were almost 128,000 new cases of COVID-19 reported in children for the week, down from 179,000 cases the week before (Dec. 24) and down from the pandemic high of 182,000 reported 2 weeks earlier (Dec.17), based on data from 49 state health departments (excluding New York), along with the District of Columbia, New York City, Puerto Rico, and Guam.

Children’s proportion of new cases for the week, 12.6%, is at its lowest point since early October after dropping for the second week in a row. The cumulative rate of COVID-19 infection, however, is now 2,828 cases per 100,000 children, up from 2,658 the previous week, the AAP and CHA said.

State-level metrics show that North Dakota has the highest cumulative rate at 7,851 per 100,000 children and Hawaii the lowest at 828. Wyoming’s cumulative proportion of child cases, 20.3%, is the highest in the country, while Florida, which uses an age range of 0-14 years for children, is the lowest at 7.1%. California’s total of 268,000 cases is almost double the number of second-place Illinois (138,000), the AAP/CHA data show.

Cumulative child deaths from COVID-19 are up to 179 in the jurisdictions reporting such data (43 states and New York City). That represents just 0.6% of all coronavirus-related deaths and has changed little over the last several months – never rising higher than 0.7% or dropping below 0.6% since early July, according to the report.

rfranki@mdedge.com

The proportion of all COVID-19 cases occurring in children, which has been rising gradually throughout the pandemic, did not rise during the week ending Dec. 31, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children’s share of the cumulative COVID-19 burden remained at 12.4% for a second consecutive week, the AAP and CHA said in their weekly report. The last full week of 2020 also marked the second consecutive drop in new cases, although that may be holiday related.

There were almost 128,000 new cases of COVID-19 reported in children for the week, down from 179,000 cases the week before (Dec. 24) and down from the pandemic high of 182,000 reported 2 weeks earlier (Dec.17), based on data from 49 state health departments (excluding New York), along with the District of Columbia, New York City, Puerto Rico, and Guam.

Children’s proportion of new cases for the week, 12.6%, is at its lowest point since early October after dropping for the second week in a row. The cumulative rate of COVID-19 infection, however, is now 2,828 cases per 100,000 children, up from 2,658 the previous week, the AAP and CHA said.

State-level metrics show that North Dakota has the highest cumulative rate at 7,851 per 100,000 children and Hawaii the lowest at 828. Wyoming’s cumulative proportion of child cases, 20.3%, is the highest in the country, while Florida, which uses an age range of 0-14 years for children, is the lowest at 7.1%. California’s total of 268,000 cases is almost double the number of second-place Illinois (138,000), the AAP/CHA data show.

Cumulative child deaths from COVID-19 are up to 179 in the jurisdictions reporting such data (43 states and New York City). That represents just 0.6% of all coronavirus-related deaths and has changed little over the last several months – never rising higher than 0.7% or dropping below 0.6% since early July, according to the report.

rfranki@mdedge.com

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

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

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

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

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

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

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

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

Agreeing to disagree

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

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

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

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

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

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

Does new variant change equation?

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

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

 

Vaccine and public resistance raised

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

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

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

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

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

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

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

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

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

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

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

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

Agreeing to disagree

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

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

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

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

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

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

Does new variant change equation?

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

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

 

Vaccine and public resistance raised

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

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

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

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

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

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

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

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

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

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

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

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

Agreeing to disagree

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

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

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

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

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

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

Does new variant change equation?

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

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

 

Vaccine and public resistance raised

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

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

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

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

Patients with heart failure who are infected with SARS-CoV-2 are at high risk for complications, with nearly 1 in 4 dying during hospitalization, according to a large database analysis that included more than 8,000 patients who had heart failure and COVID-19.

Floaria Bicher/iStock/Getty Images Plus

In-hospital mortality was 24.2% for patients who had a history of heart failure and were hospitalized with COVID-19, as compared with 14.2% for individuals without heart failure who were hospitalized with COVID-19.

For perspective, the researchers compared the patients with heart failure and COVID-19 with patients who had a history of heart failure and were hospitalized for an acute worsening episode: the risk for death was about 10-fold higher with COVID-19.

“These patients really face remarkably high risk, and when we compare that to the risk of in-hospital death with something we are a lot more familiar with – acute heart failure – we see that the risk was about 10-fold greater,” said first author Ankeet S. Bhatt, MD, MBA, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

In an article published online in JACC Heart Failure on Dec. 28, a group led by Dr. Bhatt and senior author Scott D. Solomon, MD, reported an analysis of administrative data on a total of 2,041,855 incident hospitalizations logged in the Premier Healthcare Database between April 1, 2020, and Sept. 30, 2020.

The Premier Healthcare Database comprises data from more than 1 billion patient encounters, which equates to approximately 1 in every 5 of all inpatient discharges in the United States.

Of 132,312 hospitalizations of patients with a history of heart failure, 23,843 (18.0%) were hospitalized with acute heart failure, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 (75.6%) were hospitalized for other reasons.

Outcomes and resource utilization were compared with 141,895 COVID-19 hospitalizations of patients who did not have heart failure.

Patients were deemed to have a history of heart failure if they were hospitalized at least once for heart failure from Jan. 1, 2019, to March 21, 2020, or had at least two heart failure outpatient visits during that period.

In a comment, Dr. Solomon noted some of the pros and cons of the data used in this study.

“Premier is a huge database, encompassing about one-quarter of all the health care facilities in the United States and one-fifth of all inpatient visits, so for that reason we’re able to look at things that are very difficult to look at in smaller hospital systems, but the data are also limited in that you don’t have as much granular detail as you might in smaller datasets,” said Dr. Solomon.

“One thing to recognize is that our data start at the point of hospital admission, so were looking only at individuals who have crossed the threshold in terms of their illness and been admitted,” he added.

Use of in-hospital resources was significantly greater for patients with heart failure hospitalized for COVID-19, compared with patients hospitalized for acute heart failure or for other reasons. This included “multifold” higher rates of ICU care (29% vs. 15%), mechanical ventilation (17% vs. 6%), and central venous catheter insertion (19% vs. 7%; P < .001 for all).

The proportion of patients who required mechanical ventilation and care in the ICU in the group with COVID-19 but who did not have no heart failure was similar to those who had both conditions.

The greater odds of in-hospital mortality among patients with both heart failure and COVID-19, compared with individuals with heart failure hospitalized for other reasons, was strongest in April, with an adjusted odds ratio of 14.48, compared with subsequent months (adjusted OR for May-September, 10.11; P for interaction < .001).

“We’re obviously not able to say with certainty what was happening in April, but I think that maybe the patients who were most vulnerable to COVID-19 may be more represented in that population, so the patients with comorbidities or who are immunosuppressed or otherwise,” said Dr. Bhatt in an interview.

“The other thing we think is that there may be a learning curve in terms of how to care for patients with acute severe respiratory illness. That includes increased institutional knowledge – like the use of prone ventilation – but also therapies that were subsequently shown to have benefit in randomized clinical trials, such as dexamethasone,” he added.

“These results should remind us to be innovative and thoughtful in our management of patients with heart failure while trying to maintain equity and good health for all,” wrote Nasrien E. Ibrahim, MD, from Massachusetts General Hospital, Boston; Ersilia DeFillipis, MD, Columbia University, New York; and Mitchel Psotka, MD, PhD, Innova Heart and Vascular Institute, Falls Church, Va., in an editorial accompanying the study.

The data emphasize the importance of ensuring equal access to services such as telemedicine, virtual visits, home nursing visits, and remote monitoring, they noted.

“As the COVID-19 pandemic rages on and disproportionately ravages socioeconomically disadvantaged communities, we should focus our efforts on strategies that minimize these inequities,” the editorialists wrote.

Dr. Solomon noted that, although Black and Hispanic patients were overrepresented in the population of heart failure patients hospitalized with COVID-19, once in the hospital, race was not a predictor of in-hospital mortality or the need for mechanical ventilation.

Dr. Bhatt has received speaker fees from Sanofi Pasteur and is supported by a National Institutes of Health/National Heart, Lung, and Blood Institute postdoctoral training grant. Dr. Solomon has received grant support and/or speaking fees from a number of companies and from the NIH/NHLBI. The editorialists disclosed no relevant financial relationships.

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

Patients with heart failure who are infected with SARS-CoV-2 are at high risk for complications, with nearly 1 in 4 dying during hospitalization, according to a large database analysis that included more than 8,000 patients who had heart failure and COVID-19.

Floaria Bicher/iStock/Getty Images Plus

In-hospital mortality was 24.2% for patients who had a history of heart failure and were hospitalized with COVID-19, as compared with 14.2% for individuals without heart failure who were hospitalized with COVID-19.

For perspective, the researchers compared the patients with heart failure and COVID-19 with patients who had a history of heart failure and were hospitalized for an acute worsening episode: the risk for death was about 10-fold higher with COVID-19.

“These patients really face remarkably high risk, and when we compare that to the risk of in-hospital death with something we are a lot more familiar with – acute heart failure – we see that the risk was about 10-fold greater,” said first author Ankeet S. Bhatt, MD, MBA, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

In an article published online in JACC Heart Failure on Dec. 28, a group led by Dr. Bhatt and senior author Scott D. Solomon, MD, reported an analysis of administrative data on a total of 2,041,855 incident hospitalizations logged in the Premier Healthcare Database between April 1, 2020, and Sept. 30, 2020.

The Premier Healthcare Database comprises data from more than 1 billion patient encounters, which equates to approximately 1 in every 5 of all inpatient discharges in the United States.

Of 132,312 hospitalizations of patients with a history of heart failure, 23,843 (18.0%) were hospitalized with acute heart failure, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 (75.6%) were hospitalized for other reasons.

Outcomes and resource utilization were compared with 141,895 COVID-19 hospitalizations of patients who did not have heart failure.

Patients were deemed to have a history of heart failure if they were hospitalized at least once for heart failure from Jan. 1, 2019, to March 21, 2020, or had at least two heart failure outpatient visits during that period.

In a comment, Dr. Solomon noted some of the pros and cons of the data used in this study.

“Premier is a huge database, encompassing about one-quarter of all the health care facilities in the United States and one-fifth of all inpatient visits, so for that reason we’re able to look at things that are very difficult to look at in smaller hospital systems, but the data are also limited in that you don’t have as much granular detail as you might in smaller datasets,” said Dr. Solomon.

“One thing to recognize is that our data start at the point of hospital admission, so were looking only at individuals who have crossed the threshold in terms of their illness and been admitted,” he added.

Use of in-hospital resources was significantly greater for patients with heart failure hospitalized for COVID-19, compared with patients hospitalized for acute heart failure or for other reasons. This included “multifold” higher rates of ICU care (29% vs. 15%), mechanical ventilation (17% vs. 6%), and central venous catheter insertion (19% vs. 7%; P < .001 for all).

The proportion of patients who required mechanical ventilation and care in the ICU in the group with COVID-19 but who did not have no heart failure was similar to those who had both conditions.

The greater odds of in-hospital mortality among patients with both heart failure and COVID-19, compared with individuals with heart failure hospitalized for other reasons, was strongest in April, with an adjusted odds ratio of 14.48, compared with subsequent months (adjusted OR for May-September, 10.11; P for interaction < .001).

“We’re obviously not able to say with certainty what was happening in April, but I think that maybe the patients who were most vulnerable to COVID-19 may be more represented in that population, so the patients with comorbidities or who are immunosuppressed or otherwise,” said Dr. Bhatt in an interview.

“The other thing we think is that there may be a learning curve in terms of how to care for patients with acute severe respiratory illness. That includes increased institutional knowledge – like the use of prone ventilation – but also therapies that were subsequently shown to have benefit in randomized clinical trials, such as dexamethasone,” he added.

“These results should remind us to be innovative and thoughtful in our management of patients with heart failure while trying to maintain equity and good health for all,” wrote Nasrien E. Ibrahim, MD, from Massachusetts General Hospital, Boston; Ersilia DeFillipis, MD, Columbia University, New York; and Mitchel Psotka, MD, PhD, Innova Heart and Vascular Institute, Falls Church, Va., in an editorial accompanying the study.

The data emphasize the importance of ensuring equal access to services such as telemedicine, virtual visits, home nursing visits, and remote monitoring, they noted.

“As the COVID-19 pandemic rages on and disproportionately ravages socioeconomically disadvantaged communities, we should focus our efforts on strategies that minimize these inequities,” the editorialists wrote.

Dr. Solomon noted that, although Black and Hispanic patients were overrepresented in the population of heart failure patients hospitalized with COVID-19, once in the hospital, race was not a predictor of in-hospital mortality or the need for mechanical ventilation.

Dr. Bhatt has received speaker fees from Sanofi Pasteur and is supported by a National Institutes of Health/National Heart, Lung, and Blood Institute postdoctoral training grant. Dr. Solomon has received grant support and/or speaking fees from a number of companies and from the NIH/NHLBI. The editorialists disclosed no relevant financial relationships.

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

Patients with heart failure who are infected with SARS-CoV-2 are at high risk for complications, with nearly 1 in 4 dying during hospitalization, according to a large database analysis that included more than 8,000 patients who had heart failure and COVID-19.

Floaria Bicher/iStock/Getty Images Plus

In-hospital mortality was 24.2% for patients who had a history of heart failure and were hospitalized with COVID-19, as compared with 14.2% for individuals without heart failure who were hospitalized with COVID-19.

For perspective, the researchers compared the patients with heart failure and COVID-19 with patients who had a history of heart failure and were hospitalized for an acute worsening episode: the risk for death was about 10-fold higher with COVID-19.

“These patients really face remarkably high risk, and when we compare that to the risk of in-hospital death with something we are a lot more familiar with – acute heart failure – we see that the risk was about 10-fold greater,” said first author Ankeet S. Bhatt, MD, MBA, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

In an article published online in JACC Heart Failure on Dec. 28, a group led by Dr. Bhatt and senior author Scott D. Solomon, MD, reported an analysis of administrative data on a total of 2,041,855 incident hospitalizations logged in the Premier Healthcare Database between April 1, 2020, and Sept. 30, 2020.

The Premier Healthcare Database comprises data from more than 1 billion patient encounters, which equates to approximately 1 in every 5 of all inpatient discharges in the United States.

Of 132,312 hospitalizations of patients with a history of heart failure, 23,843 (18.0%) were hospitalized with acute heart failure, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 (75.6%) were hospitalized for other reasons.

Outcomes and resource utilization were compared with 141,895 COVID-19 hospitalizations of patients who did not have heart failure.

Patients were deemed to have a history of heart failure if they were hospitalized at least once for heart failure from Jan. 1, 2019, to March 21, 2020, or had at least two heart failure outpatient visits during that period.

In a comment, Dr. Solomon noted some of the pros and cons of the data used in this study.

“Premier is a huge database, encompassing about one-quarter of all the health care facilities in the United States and one-fifth of all inpatient visits, so for that reason we’re able to look at things that are very difficult to look at in smaller hospital systems, but the data are also limited in that you don’t have as much granular detail as you might in smaller datasets,” said Dr. Solomon.

“One thing to recognize is that our data start at the point of hospital admission, so were looking only at individuals who have crossed the threshold in terms of their illness and been admitted,” he added.

Use of in-hospital resources was significantly greater for patients with heart failure hospitalized for COVID-19, compared with patients hospitalized for acute heart failure or for other reasons. This included “multifold” higher rates of ICU care (29% vs. 15%), mechanical ventilation (17% vs. 6%), and central venous catheter insertion (19% vs. 7%; P < .001 for all).

The proportion of patients who required mechanical ventilation and care in the ICU in the group with COVID-19 but who did not have no heart failure was similar to those who had both conditions.

The greater odds of in-hospital mortality among patients with both heart failure and COVID-19, compared with individuals with heart failure hospitalized for other reasons, was strongest in April, with an adjusted odds ratio of 14.48, compared with subsequent months (adjusted OR for May-September, 10.11; P for interaction < .001).

“We’re obviously not able to say with certainty what was happening in April, but I think that maybe the patients who were most vulnerable to COVID-19 may be more represented in that population, so the patients with comorbidities or who are immunosuppressed or otherwise,” said Dr. Bhatt in an interview.

“The other thing we think is that there may be a learning curve in terms of how to care for patients with acute severe respiratory illness. That includes increased institutional knowledge – like the use of prone ventilation – but also therapies that were subsequently shown to have benefit in randomized clinical trials, such as dexamethasone,” he added.

“These results should remind us to be innovative and thoughtful in our management of patients with heart failure while trying to maintain equity and good health for all,” wrote Nasrien E. Ibrahim, MD, from Massachusetts General Hospital, Boston; Ersilia DeFillipis, MD, Columbia University, New York; and Mitchel Psotka, MD, PhD, Innova Heart and Vascular Institute, Falls Church, Va., in an editorial accompanying the study.

The data emphasize the importance of ensuring equal access to services such as telemedicine, virtual visits, home nursing visits, and remote monitoring, they noted.

“As the COVID-19 pandemic rages on and disproportionately ravages socioeconomically disadvantaged communities, we should focus our efforts on strategies that minimize these inequities,” the editorialists wrote.

Dr. Solomon noted that, although Black and Hispanic patients were overrepresented in the population of heart failure patients hospitalized with COVID-19, once in the hospital, race was not a predictor of in-hospital mortality or the need for mechanical ventilation.

Dr. Bhatt has received speaker fees from Sanofi Pasteur and is supported by a National Institutes of Health/National Heart, Lung, and Blood Institute postdoctoral training grant. Dr. Solomon has received grant support and/or speaking fees from a number of companies and from the NIH/NHLBI. The editorialists disclosed no relevant financial relationships.

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

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

Researchers in Madrid may have found a clue to the pathogenesis of ST-segment elevation myocardial infarction (STEMI) in patients with COVID-19; it might also offer a therapeutic target to counter the hypercoagulability seen with COVID-19.

In a case series of five patients with COVID-19 who had an STEMI, neutrophil extracellular traps (NETs) were detected in coronary thrombi of all five patients. The median density was 66%, which is significantly higher than that seen in a historical series of patients with STEMI. In that series, NETs were found in only two-thirds of patients; in that series, the median density was 19%.

In the patients with COVID-19 and STEMI and in the patients reported in the prepandemic historical series from 2015, intracoronary aspirates were obtained during percutaneous coronary intervention using a thrombus aspiration device.

Histologically, findings in the patients from 2015 differed from those of patients with COVID-19. In the patients with COVID, thrombi were composed mostly of fibrin and polymorphonuclear cells. None showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. In contrast, 65% of thrombi from the 2015 series contained plaque fragments.

Ana Blasco, MD, PhD, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, and colleagues report their findings in an article published online Dec. 29 in JAMA Cardiology.

Commenting on the findings in an interview, Irene Lang, MD, from the Medical University of Vienna said, “This is really a very small series, purely observational, and suffering from the problem that acute STEMI is uncommon in COVID-19, but it does serve to demonstrate once more the abundance of NETs in acute myocardial infarction.”

“NETs are very much at the cutting edge of thrombosis research, and NET formation provides yet another link between inflammation and clot formation,” added Peter Libby, MD, from Harvard Medical School and Brigham and Women’s Hospital, Boston.

“Multiple observations have shown thrombosis of arteries large and small, microvessels, and veins in COVID-19. The observations of Blasco et al. add to the growing literature about NETs as contributors to the havoc wrought in multiple organs in advanced COVID-19,” he added in an email exchange with this news organization.

Neither Dr. Lang nor Dr. Libby were involved in this research; both have been actively studying NETs and their contribution to cardiothrombotic disease in recent years.

NETs are newly recognized contributors to venous and arterial thrombosis. These weblike DNA strands are extruded by activated or dying neutrophils and have protein mediators that ensnare pathogens while minimizing damage to the host cell.

First described in 2004, exaggerated NET formation has also been linked to the initiation and accretion of inflammation and thrombosis.

“NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases,” Dr. Libby and his coauthors wrote in an article on the topic published in Circulation Research earlier this year.

Limiting NET formation or “dissolving” existing NETs could provide a therapeutic avenue not just for patients with COVID-19 but for all patients with thrombotic disease.

“The concept of NETs as a therapeutic target is appealing, in and out of COVID times,” said Dr. Lang.

“I personally believe that the work helps to raise awareness for the potential use of deoxyribonuclease (DNase), an enzyme that acts to clear NETs by dissolving the DNA strands, in the acute treatment of STEMI. Rapid injection of engineered recombinant DNases could potentially wipe away coronary obstructions, ideally before they may cause damage to the myocardium,” she added.

Dr. Blasco and colleagues and Dr. Lang have disclosed no relevant financial relationships. Dr. Libby is an unpaid consultant or member of the advisory board for a number of companies.

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

The COVID-19 vaccine distribution process in the United States is moving more slowly than anticipated, falling short of Operation Warp Speed’s goal to vaccinate 20 million Americans by the end of the year.

If the current pace of vaccination continues, “it’s going to take years, not months, to vaccinate the American people,” President-elect Joe Biden said during a briefing Dec. 29.

In fact, at the current rate, it would take nearly 10 years to vaccinate enough Americans to bring the pandemic under control, according to NBC News. To reach 80% of the country by late June, 3 million people would need to receive a COVID-19 vaccine each day.

“As I long feared and warned, the effort to distribute and administer the vaccine is not progressing as it should,” Mr. Biden said, reemphasizing his pledge to get 100 million doses to Americans during his first 100 days as president.

So far, 11.4 million doses have been distributed and 2.1 million people have received a vaccine, according to the Centers for Disease Control and Prevention. Most states have administered a fraction of the doses they’ve received, according to data compiled by The New York Times.

Federal officials have said there’s an “expected lag” between delivery of doses, shots going into arms, and the data being reported to the CDC, according to CNN. The Food and Drug Administration must assess each shipment for quality control, which has slowed down distribution, and the CDC data are just now beginning to include the Moderna vaccine, which the FDA authorized for emergency use on Dec. 18.

The 2.1 million number is “an underestimate,” Brett Giroir, MD, the assistant secretary of the U.S. Department of Health & Human Services, told NBC News Dec. 29. At the same time, the U.S. won’t meet the goal of vaccinating 20 million people in the next few days, he said.

Another 30 million doses will go out in January, Dr. Giroir said, followed by 50 million in February.

Some vaccine experts have said they’re not surprised by the speed of vaccine distribution.

“It had to go this way,” Paul Offit, MD, a professor of pediatrics at Children’s Hospital of Philadelphia, told STAT. “We had to trip and fall and stumble and figure this out.”

To speed up distribution in 2021, the federal government will need to help states, Mr. Biden said Dec. 29. He plans to use the Defense Authorization Act to ramp up production of vaccine supplies. Even still, the process will take months, he said.

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

The COVID-19 vaccine distribution process in the United States is moving more slowly than anticipated, falling short of Operation Warp Speed’s goal to vaccinate 20 million Americans by the end of the year.

If the current pace of vaccination continues, “it’s going to take years, not months, to vaccinate the American people,” President-elect Joe Biden said during a briefing Dec. 29.

In fact, at the current rate, it would take nearly 10 years to vaccinate enough Americans to bring the pandemic under control, according to NBC News. To reach 80% of the country by late June, 3 million people would need to receive a COVID-19 vaccine each day.

“As I long feared and warned, the effort to distribute and administer the vaccine is not progressing as it should,” Mr. Biden said, reemphasizing his pledge to get 100 million doses to Americans during his first 100 days as president.

So far, 11.4 million doses have been distributed and 2.1 million people have received a vaccine, according to the Centers for Disease Control and Prevention. Most states have administered a fraction of the doses they’ve received, according to data compiled by The New York Times.

Federal officials have said there’s an “expected lag” between delivery of doses, shots going into arms, and the data being reported to the CDC, according to CNN. The Food and Drug Administration must assess each shipment for quality control, which has slowed down distribution, and the CDC data are just now beginning to include the Moderna vaccine, which the FDA authorized for emergency use on Dec. 18.

The 2.1 million number is “an underestimate,” Brett Giroir, MD, the assistant secretary of the U.S. Department of Health & Human Services, told NBC News Dec. 29. At the same time, the U.S. won’t meet the goal of vaccinating 20 million people in the next few days, he said.

Another 30 million doses will go out in January, Dr. Giroir said, followed by 50 million in February.

Some vaccine experts have said they’re not surprised by the speed of vaccine distribution.

“It had to go this way,” Paul Offit, MD, a professor of pediatrics at Children’s Hospital of Philadelphia, told STAT. “We had to trip and fall and stumble and figure this out.”

To speed up distribution in 2021, the federal government will need to help states, Mr. Biden said Dec. 29. He plans to use the Defense Authorization Act to ramp up production of vaccine supplies. Even still, the process will take months, he said.

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

The COVID-19 vaccine distribution process in the United States is moving more slowly than anticipated, falling short of Operation Warp Speed’s goal to vaccinate 20 million Americans by the end of the year.

If the current pace of vaccination continues, “it’s going to take years, not months, to vaccinate the American people,” President-elect Joe Biden said during a briefing Dec. 29.

In fact, at the current rate, it would take nearly 10 years to vaccinate enough Americans to bring the pandemic under control, according to NBC News. To reach 80% of the country by late June, 3 million people would need to receive a COVID-19 vaccine each day.

“As I long feared and warned, the effort to distribute and administer the vaccine is not progressing as it should,” Mr. Biden said, reemphasizing his pledge to get 100 million doses to Americans during his first 100 days as president.

So far, 11.4 million doses have been distributed and 2.1 million people have received a vaccine, according to the Centers for Disease Control and Prevention. Most states have administered a fraction of the doses they’ve received, according to data compiled by The New York Times.

Federal officials have said there’s an “expected lag” between delivery of doses, shots going into arms, and the data being reported to the CDC, according to CNN. The Food and Drug Administration must assess each shipment for quality control, which has slowed down distribution, and the CDC data are just now beginning to include the Moderna vaccine, which the FDA authorized for emergency use on Dec. 18.

The 2.1 million number is “an underestimate,” Brett Giroir, MD, the assistant secretary of the U.S. Department of Health & Human Services, told NBC News Dec. 29. At the same time, the U.S. won’t meet the goal of vaccinating 20 million people in the next few days, he said.

Another 30 million doses will go out in January, Dr. Giroir said, followed by 50 million in February.

Some vaccine experts have said they’re not surprised by the speed of vaccine distribution.

“It had to go this way,” Paul Offit, MD, a professor of pediatrics at Children’s Hospital of Philadelphia, told STAT. “We had to trip and fall and stumble and figure this out.”

To speed up distribution in 2021, the federal government will need to help states, Mr. Biden said Dec. 29. He plans to use the Defense Authorization Act to ramp up production of vaccine supplies. Even still, the process will take months, he said.

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

A scoring system based on 10 parameters in a complete blood count with differential within 3 days of hospital presentation predict those with COVID-19 who are most likely to progress to critical illness, new evidence shows.

Advantages include prognosis based on a common and inexpensive clinical measure, as well as automatic generation of the score along with CBC results, noted investigators in the observational study conducted throughout 11 European hospitals.

“COVID-19 comes along with specific alterations in circulating blood cells that can be detected by a routine hematology analyzer, especially when that hematology analyzer is also capable to recognize activated immune cells and early circulating blood cells, such as erythroblast and immature granulocytes,” senior author Andre van der Ven, MD, PhD, infectious diseases specialist and professor of international health at Radboud University Medical Center’s Center for Infectious Diseases in Nijmegen, the Netherlands, said in an interview.

Furthermore, Dr. van der Ven said, “these specific changes are also seen in the early course of COVID-19 disease, and more in those that will develop serious disease compared to those with mild disease.”

The study was published online Dec. 21 in the journal eLife.

The study is “almost instinctively correct. It’s basically what clinicians do informally with complete blood count … looking at a combination of results to get the gestalt of what patients are going through,” Samuel Reichberg, MD, PhD, associate medical director of the Northwell Health Core Laboratory in Lake Success, N.Y., said in an interview.

“This is something that begs to be done for COVID-19. I’m surprised no one has done this before,” he added.

Dr. Van der Ven and colleagues created an algorithm based on 1,587 CBC assays from 923 adults. They also validated the scoring system in a second cohort of 217 CBC measurements in 202 people. The findings were concordant – the score accurately predicted the need for critical care within 14 days in 70.5% of the development cohort and 72% of the validation group.

The scoring system was superior to any of the 10 parameters alone. Over 14 days, the majority of those classified as noncritical within the first 3 days remained clinically stable, whereas the “clinical illness” group progressed. Clinical severity peaked on day 6.

Most previous COVID-19 prognosis research was geographically limited, carried a high risk for bias and/or did not validate the findings, Dr. Van der Ven and colleagues noted.
 

Early identification, early intervention

The aim of the score is “to assist with objective risk stratification to support patient management decision-making early on, and thus facilitate timely interventions, such as need for ICU or not, before symptoms of severe illness become clinically overt, with the intention to improve patient outcomes, and not to predict mortality,” the investigators noted.

Dr. Van der Ven and colleagues developed the score based on adults presenting from Feb. 21 to April 6, with outcomes followed until June 9. Median age of the 982 patients was 71 years and approximately two-thirds were men. They used a Sysmex Europe XN-1000 (Hamburg, Germany) hemocytometric analyzer in the study.

Only 7% of this cohort was not admitted to a hospital. Another 74% were admitted to a general ward and the remaining 19% were transferred directly to the ICU.

The scoring system includes parameters for neutrophils, monocytes, red blood cells and immature granulocytes, and when available, reticulocyte and iron bioavailability measures.

The researchers report significant differences over time in the neutrophil-to-lymphocyte ratio between the critical illness and noncritical groups (P < .001), for example. They also found significant differences in hemoglobin levels between cohorts after day 5.

The system generates a score from 0 to 28. Sensitivity for correctly predicting the need for critical care increased from 62% on day 1 to 93% on day 6. 
 

A more objective assessment of risk

The study demonstrated that SARS-CoV-2 infection is characterized by hemocytometric changes over time. These changes, reflected together in the prognostic score, could aid in the early identification of patients whose clinical course is more likely to deteriorate over time.

The findings also support other work that shows men are more likely to present to the hospital with COVID-19, and that older age and presence of comorbidities add to overall risk. “However,” the researchers noted, “not all young patients had a mild course, and not all old patients with comorbidities were critical.”

Therefore, the prognostic score can help identify patients at risk for severe progression outside other risk factors and “support individualized treatment decisions with objective data,” they added.

Dr. Reichberg called the concept of combining CBC parameters into one score “very valuable.” However, he added that incorporating an index into clinical practice “has historically been tricky.”

The results “probably have to be replicated,” Dr. Reichberg said.

He added that it is likely a CBC-based score will be combined with other measures. “I would like to see an index that combines all the tests we do [for COVID-19], including complete blood count.”

Dr. Van der Ven shared the next step in his research. “The algorithm should be installed on the hematology analyzers so the prognostic score will be automatically generated if a full blood count is asked for in a COVID-19 patient,” he said. “So implementation of score is the main focus now.”

Dr. van der Ven disclosed an ad hoc consultancy agreement with Sysmex Europe. Sysmex Europe provided the reagents in the study free of charge; no other funders were involved. Dr. Reichberg has disclosed no relevant financial relationships.

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

A scoring system based on 10 parameters in a complete blood count with differential within 3 days of hospital presentation predict those with COVID-19 who are most likely to progress to critical illness, new evidence shows.

Advantages include prognosis based on a common and inexpensive clinical measure, as well as automatic generation of the score along with CBC results, noted investigators in the observational study conducted throughout 11 European hospitals.

“COVID-19 comes along with specific alterations in circulating blood cells that can be detected by a routine hematology analyzer, especially when that hematology analyzer is also capable to recognize activated immune cells and early circulating blood cells, such as erythroblast and immature granulocytes,” senior author Andre van der Ven, MD, PhD, infectious diseases specialist and professor of international health at Radboud University Medical Center’s Center for Infectious Diseases in Nijmegen, the Netherlands, said in an interview.

Furthermore, Dr. van der Ven said, “these specific changes are also seen in the early course of COVID-19 disease, and more in those that will develop serious disease compared to those with mild disease.”

The study was published online Dec. 21 in the journal eLife.

The study is “almost instinctively correct. It’s basically what clinicians do informally with complete blood count … looking at a combination of results to get the gestalt of what patients are going through,” Samuel Reichberg, MD, PhD, associate medical director of the Northwell Health Core Laboratory in Lake Success, N.Y., said in an interview.

“This is something that begs to be done for COVID-19. I’m surprised no one has done this before,” he added.

Dr. Van der Ven and colleagues created an algorithm based on 1,587 CBC assays from 923 adults. They also validated the scoring system in a second cohort of 217 CBC measurements in 202 people. The findings were concordant – the score accurately predicted the need for critical care within 14 days in 70.5% of the development cohort and 72% of the validation group.

The scoring system was superior to any of the 10 parameters alone. Over 14 days, the majority of those classified as noncritical within the first 3 days remained clinically stable, whereas the “clinical illness” group progressed. Clinical severity peaked on day 6.

Most previous COVID-19 prognosis research was geographically limited, carried a high risk for bias and/or did not validate the findings, Dr. Van der Ven and colleagues noted.
 

Early identification, early intervention

The aim of the score is “to assist with objective risk stratification to support patient management decision-making early on, and thus facilitate timely interventions, such as need for ICU or not, before symptoms of severe illness become clinically overt, with the intention to improve patient outcomes, and not to predict mortality,” the investigators noted.

Dr. Van der Ven and colleagues developed the score based on adults presenting from Feb. 21 to April 6, with outcomes followed until June 9. Median age of the 982 patients was 71 years and approximately two-thirds were men. They used a Sysmex Europe XN-1000 (Hamburg, Germany) hemocytometric analyzer in the study.

Only 7% of this cohort was not admitted to a hospital. Another 74% were admitted to a general ward and the remaining 19% were transferred directly to the ICU.

The scoring system includes parameters for neutrophils, monocytes, red blood cells and immature granulocytes, and when available, reticulocyte and iron bioavailability measures.

The researchers report significant differences over time in the neutrophil-to-lymphocyte ratio between the critical illness and noncritical groups (P < .001), for example. They also found significant differences in hemoglobin levels between cohorts after day 5.

The system generates a score from 0 to 28. Sensitivity for correctly predicting the need for critical care increased from 62% on day 1 to 93% on day 6. 
 

A more objective assessment of risk

The study demonstrated that SARS-CoV-2 infection is characterized by hemocytometric changes over time. These changes, reflected together in the prognostic score, could aid in the early identification of patients whose clinical course is more likely to deteriorate over time.

The findings also support other work that shows men are more likely to present to the hospital with COVID-19, and that older age and presence of comorbidities add to overall risk. “However,” the researchers noted, “not all young patients had a mild course, and not all old patients with comorbidities were critical.”

Therefore, the prognostic score can help identify patients at risk for severe progression outside other risk factors and “support individualized treatment decisions with objective data,” they added.

Dr. Reichberg called the concept of combining CBC parameters into one score “very valuable.” However, he added that incorporating an index into clinical practice “has historically been tricky.”

The results “probably have to be replicated,” Dr. Reichberg said.

He added that it is likely a CBC-based score will be combined with other measures. “I would like to see an index that combines all the tests we do [for COVID-19], including complete blood count.”

Dr. Van der Ven shared the next step in his research. “The algorithm should be installed on the hematology analyzers so the prognostic score will be automatically generated if a full blood count is asked for in a COVID-19 patient,” he said. “So implementation of score is the main focus now.”

Dr. van der Ven disclosed an ad hoc consultancy agreement with Sysmex Europe. Sysmex Europe provided the reagents in the study free of charge; no other funders were involved. Dr. Reichberg has disclosed no relevant financial relationships.

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

A scoring system based on 10 parameters in a complete blood count with differential within 3 days of hospital presentation predict those with COVID-19 who are most likely to progress to critical illness, new evidence shows.

Advantages include prognosis based on a common and inexpensive clinical measure, as well as automatic generation of the score along with CBC results, noted investigators in the observational study conducted throughout 11 European hospitals.

“COVID-19 comes along with specific alterations in circulating blood cells that can be detected by a routine hematology analyzer, especially when that hematology analyzer is also capable to recognize activated immune cells and early circulating blood cells, such as erythroblast and immature granulocytes,” senior author Andre van der Ven, MD, PhD, infectious diseases specialist and professor of international health at Radboud University Medical Center’s Center for Infectious Diseases in Nijmegen, the Netherlands, said in an interview.

Furthermore, Dr. van der Ven said, “these specific changes are also seen in the early course of COVID-19 disease, and more in those that will develop serious disease compared to those with mild disease.”

The study was published online Dec. 21 in the journal eLife.

The study is “almost instinctively correct. It’s basically what clinicians do informally with complete blood count … looking at a combination of results to get the gestalt of what patients are going through,” Samuel Reichberg, MD, PhD, associate medical director of the Northwell Health Core Laboratory in Lake Success, N.Y., said in an interview.

“This is something that begs to be done for COVID-19. I’m surprised no one has done this before,” he added.

Dr. Van der Ven and colleagues created an algorithm based on 1,587 CBC assays from 923 adults. They also validated the scoring system in a second cohort of 217 CBC measurements in 202 people. The findings were concordant – the score accurately predicted the need for critical care within 14 days in 70.5% of the development cohort and 72% of the validation group.

The scoring system was superior to any of the 10 parameters alone. Over 14 days, the majority of those classified as noncritical within the first 3 days remained clinically stable, whereas the “clinical illness” group progressed. Clinical severity peaked on day 6.

Most previous COVID-19 prognosis research was geographically limited, carried a high risk for bias and/or did not validate the findings, Dr. Van der Ven and colleagues noted.
 

Early identification, early intervention

The aim of the score is “to assist with objective risk stratification to support patient management decision-making early on, and thus facilitate timely interventions, such as need for ICU or not, before symptoms of severe illness become clinically overt, with the intention to improve patient outcomes, and not to predict mortality,” the investigators noted.

Dr. Van der Ven and colleagues developed the score based on adults presenting from Feb. 21 to April 6, with outcomes followed until June 9. Median age of the 982 patients was 71 years and approximately two-thirds were men. They used a Sysmex Europe XN-1000 (Hamburg, Germany) hemocytometric analyzer in the study.

Only 7% of this cohort was not admitted to a hospital. Another 74% were admitted to a general ward and the remaining 19% were transferred directly to the ICU.

The scoring system includes parameters for neutrophils, monocytes, red blood cells and immature granulocytes, and when available, reticulocyte and iron bioavailability measures.

The researchers report significant differences over time in the neutrophil-to-lymphocyte ratio between the critical illness and noncritical groups (P < .001), for example. They also found significant differences in hemoglobin levels between cohorts after day 5.

The system generates a score from 0 to 28. Sensitivity for correctly predicting the need for critical care increased from 62% on day 1 to 93% on day 6. 
 

A more objective assessment of risk

The study demonstrated that SARS-CoV-2 infection is characterized by hemocytometric changes over time. These changes, reflected together in the prognostic score, could aid in the early identification of patients whose clinical course is more likely to deteriorate over time.

The findings also support other work that shows men are more likely to present to the hospital with COVID-19, and that older age and presence of comorbidities add to overall risk. “However,” the researchers noted, “not all young patients had a mild course, and not all old patients with comorbidities were critical.”

Therefore, the prognostic score can help identify patients at risk for severe progression outside other risk factors and “support individualized treatment decisions with objective data,” they added.

Dr. Reichberg called the concept of combining CBC parameters into one score “very valuable.” However, he added that incorporating an index into clinical practice “has historically been tricky.”

The results “probably have to be replicated,” Dr. Reichberg said.

He added that it is likely a CBC-based score will be combined with other measures. “I would like to see an index that combines all the tests we do [for COVID-19], including complete blood count.”

Dr. Van der Ven shared the next step in his research. “The algorithm should be installed on the hematology analyzers so the prognostic score will be automatically generated if a full blood count is asked for in a COVID-19 patient,” he said. “So implementation of score is the main focus now.”

Dr. van der Ven disclosed an ad hoc consultancy agreement with Sysmex Europe. Sysmex Europe provided the reagents in the study free of charge; no other funders were involved. Dr. Reichberg has disclosed no relevant financial relationships.

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

The United States exceeded 2 million reported cases of COVID-19 in children just 6 weeks after recording its 1 millionth case, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of cases in children was 2,000,681 as of Dec. 24, which represents 12.4% of all cases reported by the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA stated Dec. 29.

The case count for just the latest week, 178,935, was actually down 1.7% from the 182,018 reported the week before, marking the second drop since the beginning of December. The first came during the week ending Dec. 3, when the number of cases dropped more than 19% from the previous week, based on data from the AAP/CHA report.

The cumulative national rate of coronavirus infection is now 2,658 cases per 100,000 children, and “13 states have reported more than 4,000 cases per 100,000,” the two groups said.

The highest rate for any state can be found in North Dakota, which has had 7,722 cases of COVID-19 per 100,000 children. Wyoming has the highest proportion of cases in children at 20.5%, and California has reported the most cases overall, 234,174, the report shows.

Data on testing, hospitalization, and mortality were not included in the Dec. 29 report because of the holiday but will be available in the next edition, scheduled for release on Jan. 5, 2021.

rfranki@mdedge.com

The United States exceeded 2 million reported cases of COVID-19 in children just 6 weeks after recording its 1 millionth case, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of cases in children was 2,000,681 as of Dec. 24, which represents 12.4% of all cases reported by the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA stated Dec. 29.

The case count for just the latest week, 178,935, was actually down 1.7% from the 182,018 reported the week before, marking the second drop since the beginning of December. The first came during the week ending Dec. 3, when the number of cases dropped more than 19% from the previous week, based on data from the AAP/CHA report.

The cumulative national rate of coronavirus infection is now 2,658 cases per 100,000 children, and “13 states have reported more than 4,000 cases per 100,000,” the two groups said.

The highest rate for any state can be found in North Dakota, which has had 7,722 cases of COVID-19 per 100,000 children. Wyoming has the highest proportion of cases in children at 20.5%, and California has reported the most cases overall, 234,174, the report shows.

Data on testing, hospitalization, and mortality were not included in the Dec. 29 report because of the holiday but will be available in the next edition, scheduled for release on Jan. 5, 2021.

rfranki@mdedge.com

The United States exceeded 2 million reported cases of COVID-19 in children just 6 weeks after recording its 1 millionth case, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of cases in children was 2,000,681 as of Dec. 24, which represents 12.4% of all cases reported by the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA stated Dec. 29.

The case count for just the latest week, 178,935, was actually down 1.7% from the 182,018 reported the week before, marking the second drop since the beginning of December. The first came during the week ending Dec. 3, when the number of cases dropped more than 19% from the previous week, based on data from the AAP/CHA report.

The cumulative national rate of coronavirus infection is now 2,658 cases per 100,000 children, and “13 states have reported more than 4,000 cases per 100,000,” the two groups said.

The highest rate for any state can be found in North Dakota, which has had 7,722 cases of COVID-19 per 100,000 children. Wyoming has the highest proportion of cases in children at 20.5%, and California has reported the most cases overall, 234,174, the report shows.

Data on testing, hospitalization, and mortality were not included in the Dec. 29 report because of the holiday but will be available in the next edition, scheduled for release on Jan. 5, 2021.

rfranki@mdedge.com