Covid ICYMI

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: A single subcutaneous dose of the antibody cocktail REGEN-COV (casirivimab plus imdevimab) is effective in preventing symptomatic and asymptomatic infection in household contacts of COVID-19-positive individuals.

Major finding: The antibody cocktail group developed fewer symptomatic SARS-CoV-2 infections than the placebo group (relative risk reduction, 81.4%). The antibody cocktail effectively prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%).

Study details: In a randomized, double-blind, placebo-controlled trial, unaffected household members (age, 12 years or older) of individuals testing positive for SARS-CoV-2 received either the antibody cocktail (n=753) or placebo (n=752).

Disclosures: The study was funded by Regeneron Pharmaceuticals, F. Hoffmann-LaRoche, and the National Institutes of Health. Several authors were employees and/or stockholders of Regeneron Pharmaceuticals.

Source: O'Brien MP et al. N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2109682.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Dapagliflozin does not improve COVID-19 hospitalization outcomes for patients with cardiometabolic risk factors.

Major finding: Dapagliflozin vs placebo failed to meet the primary composite outcome of organ dysfunction or all-cause death (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10). There was no difference in the rates of new/worsened organ dysfunction, deaths, or clinical improvement between the groups.

Study details: In the DARE-19 phase 3 trial, patients were randomly assigned to receive either dapagliflozin (n=625) or placebo (n=625).

Disclosures: The study was funded by AstraZeneca. R Esterline, J Oscarsson, SB Gasparyan, J Buenconsejo, AM Langkilde, and P Ambery are employees and stockholders of AstraZeneca. M Aboudara, E Akin, WKS Barroso, ADM Feitosa, CRH Filho, A Fonseca, K Gosch, RA Gordon, CP Jaeger, LN Maia, DDF Moia, JRL Soto, F Tang, SL Windsor, O Mukhtar, V Chopra, RVP Soares, V Garla, PE Leaes, FS Silveira, and M Pursley declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Kosiborod MN et al. Lancet Diabetes Endocrinol. 2021 Jul 21. doi: 10.1016/S2213-8587(21)00180-7.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Canakinumab does not improve survival in hospitalized patients with severe COVID-19.

Major finding: There was no significant difference in survival without invasive mechanical ventilation between days 3 and 29 with canakinumab vs. placebo (88.8% vs. 85.7%; rate difference, 3.1 percentage points; 95% confidence interval [CI], −3.1 to 9.3). COVID-19 mortality also did not differ with canakinumab vs. placebo (4.9% vs 7.2%; rate difference, −2.3 percentage points; 95% CI, −6.7 to 2.2).

Study details: The data come from the randomized, double-blind, placebo-controlled phase 3 CAN-COVID trial (n=454).

Disclosures: The study was sponsored by Novartis Pharma AG, Basel, Switzerland. All authors received funding from Novartis during the conduct of the study. The authors also reported relationships with other pharmaceutical companies.

Source: Caricchio R et al. JAMA. 2021 Jul 20. doi: 10.1001/jama.2021.9508.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Inhaled budesonide is associated with a shorter time to recovery but fails to reduce the risk for hospitalization or death in high-risk primary care patients with COVID-19.

Major finding: Budesonide vs usual care was associated with a shorter time to recovery (11.8 days vs 14.7 days). Budesonide was associated with a nonsignificant 2.0% reduction in hospitalization or death compared with usual care.

Study details: The data come from the PRINCIPLE trial, where 2,530 patients were randomly assigned to either inhaled budesonide (n=787), usual care alone (n=1,069), or usual care plus other interventions (n=674).

Disclosures: The study was funded by the National Institute of Health Research and United Kingdom Research Innovation. M Bafadhel, D Richards, BR Saville, N Berry, MA Detry, M Fitzgerald, S de Lusignan, MI Andersson, PJ Barnes, REK Russell, S Ramakrishnan, FDR Hobbs, and CC Butler reported relationships with pharmaceutical companies and/or research institutions. The remaining authors declared no conflict of interests.

Source: Yu LM et al. Lancet. 2021 Aug 10. doi: 10.1016/S0140-6736(21)01744-X.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Presence of pulmonary embolism (PE) is not associated with increased mortality in patients with COVID-19 risk.

Major finding: Risk factors for PE in patients with COVID-19 included male sex, mechanical ventilation, intensive care unit admission, and circulating D-dimer. Patients with PE did not have an increased risk for mortality compared with those without PE (odds ratio, 1.31; P = .25).

Study details: The data come from a meta-analysis of 16 cohort studies involving 5,826 patients with COVID-19.

Disclosures: No funding information was available. The authors declared no conflict of interests.

Source: Gómez CA et al. Sci Rep. 2021 Aug 6. doi: 10.1038/s41598-021-95512-7.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Administration of convalescent plasma within 7 days of symptom onset fails to prevent disease progression in acutely ill, high-risk patients with COVID-19.

Major finding: There was no difference between the convalescent plasma group and the placebo group in disease progression (30.0% vs 31.9%; risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8).

Study details: The multicenter, single-blind SIREN-C3PO trial included patients with COVID-19 (n=511) randomly assigned to receive either plasma or placebo in the emergency department.

Disclosures: The study was supported by the National Institutes of Health, the Biomedical Advanced Research and Development Authority, and the Operation Warp Speed interagency program. D Beiser, A Burnett R Davenport, L Dumont, V Durkalski-Mauldin, N El Kassar, L Foster, C Greineder, N Haas, J Hah, A Kaplan, B Kea, F Korley, E Lowell, J McDyer, J Quinn, J Reynolds, R Silbergleit, C Van Huysen, and K Yadav declared no conflict of interests. The remaining authors disclosed relationships with pharmaceutical companies and/or research institutions.

Source: Korley FK et al. N Engl J Med. 2021 Aug 18. doi: 10.1056/NEJMoa2103784.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.

Key clinical point: Addition of baricitinib to standard of care treatment may reduce 28-day mortality risk in patients hospitalized with COVID-19, but does not significantly reduce the frequency of disease progression.

Major finding: There was a 38.2% relative reduction in 28-day all-cause mortality risk with baricitinib vs placebo. There was no significant difference between the baricitinib and placebo groups in the primary composite endpoint of disease progression outcomes (odds ratio, 0.85; P = .18).

Study details: In a phase 3, double-blind trial, hospitalized patients with COVID-19 receiving standard of care were randomly assigned to either baricitinib (n=764) or placebo group (n=761).

Disclosures: The study was funded by Eli Lilly and Company. S de Bono, CE Kartman, V Krishnan, R Liao, MLB Piruzeli, A Cardose, S Chakladar, B Crowe, P Reis, X Zhang, and DH Adams are employees and shareholders of Eli Lilly and Company. RD Pellegrini declared no conflict of interests. Other authors reported relationships with pharmaceutical companies including Eli Lilly and Company.

Source: Marconi VC et al. Lancet Respir Med. 2021 Sep 1. doi: 10.1016/S2213-2600(21)00331-3.

Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.

Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).

Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.

Disclosures: This study was self-funded. The authors declared no conflict of interests.

Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.

Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.

Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).

Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.

Disclosures: This study was self-funded. The authors declared no conflict of interests.

Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.

Key clinical point: Individuals with asthma have a 17% lower risk for COVID-19 infection than those without asthma.

Major finding: Individuals with asthma had a lower risk for COVID-19 infection (risk ratio [RR], 0.83; P = .01), but not for COVID-19-related hospitalization (RR, 1.18; P = .08), intensive care unit admission (RR, 1.21; P = .09), and ICU admission (RR, 1.06; P = .65).

Study details: The data come from a meta-analysis of 51 studies involving 965,551 individuals with and without asthma who tested positive for COVID-19.

Disclosures: This study was self-funded. The authors declared no conflict of interests.

Source: Sunjaya AP et al. Eur Respir J. 2021 Aug 24. doi: 10.1183/13993003.01209-2021.

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

One week after reporting promising results from the trial of their COVID-19 vaccine in children ages 5-11, Pfizer and BioNTech announced they’d submitted the data to the Food and Drug Administration. But that hasn’t stopped some parents from discreetly getting their children under age 12 vaccinated.

“The FDA, you never want to get ahead of their judgment,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, told MSNBC on Sept. 28. “But I would imagine in the next few weeks, they will examine that data and hopefully they’ll give the okay so that we can start vaccinating children, hopefully before the end of October.”
 

Lying to vaccinate now

More than half of all parents with children under 12 say they plan to get their kids vaccinated, according to a Gallup poll. Among those who say they’re “very worried” or “somewhat worried” about their children catching COVID, that number goes up to 90% and 72%, respectively.

And although the FDA and the American Academy of Pediatrics have warned against it, some parents whose children can pass for 12 have lied to get them vaccinated already.

Dawn G. is a mom of two in southwest Missouri, where less than 45% of the population has been fully vaccinated. Her son turns 12 in early October, but in-person school started in mid-August.

“It was scary, thinking of him going to school for even 2 months,” she said. “Some parents thought their kid had a low chance of getting COVID, and their kid died. Nobody expects it to be them.”

In July, she and her husband took their son to a walk-in clinic and lied about his age.

“So many things can happen, from bullying to school shootings, and now this added pandemic risk,” she said. “I’ll do anything I can to protect my child, and a birthdate seems so arbitrary. He’ll be 12 in a matter of weeks. It seems ridiculous that that date would stop me from protecting him.”

In northern California, Carrie S. had a similar thought. When the vaccine was authorized for children ages 12-15 in May, the older of her two children got the shot right away. But her youngest doesn’t turn 12 until November.

“We were tempted to get the younger one vaccinated in May, but it didn’t seem like a rush. We were willing to wait to get the dosage right,” she ssaid. “But as Delta came through, there were no options for online school, the CDC was dropping mask expectations –it seemed like the world was ready to forget the pandemic was happening. It seemed like the least-bad option to get her vaccinated so she could go back to school, and we could find some balance of risk in our lives.”
 

Adult vs. pediatric doses

For now, experts advise against getting younger children vaccinated, even those who are the size of an adult, because of the way the human immune system develops.

“It’s not really about size,” said Anne Liu, MD, an immunologist and pediatrics professor at Stanford (Calif.) University. “The immune system behaves differently at different ages. Younger kids tend to have a more exuberant innate immune system, which is the part of the immune system that senses danger, even before it has developed a memory response.”

The adult Pfizer-BioNTech vaccine contains 30 mcg of mRNA, while the pediatric dose is just 10 mcg. That smaller dose produces an immune response similar to what’s seen in adults who receive 30 mcg, according to Pfizer.

“We were one of the sites that was involved in the phase 1 trial, a lot of times that’s called a dose-finding trial,” said Michael Smith, MD, a coinvestigator for the COVID vaccine trials done at Duke University. “And basically, if younger kids got a higher dose, they had more of a reaction, so it hurt more. They had fever, they had more redness and swelling at the site of the injection, and they just felt lousy, more than at the lower doses.”

At this point, with Pfizer’s data showing that younger children need a smaller dose, it doesn’t make sense to lie about your child’s age, said Dr. Smith.

“If my two options were having my child get the infection versus getting the vaccine, I’d get the vaccine. But we’re a few weeks away from getting the lower dose approved in kids,” he said. “It’s certainly safer. I don’t expect major, lifelong side effects from the higher dose, but it’s going to hurt, your kid’s going to have a fever, they’re going to feel lousy for a couple days, and they just don’t need that much antigen.”

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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