Reassuring data about the safety of the vaccines was provided by two recent studies. The first, published by the New England Journal of Medicine on Aug. 25, compared 884,828 patients in Israel who received the Pfizer-BioNTech vaccine to an equal number of unvaccinated controls to identify any adverse events. Most studied events were no different, but vaccinated patients did have significantly elevated risk of myocarditis (risk ratio, 3.24; 95% CI, 1.55 to 12.44), as well as higher rates of lymphadenopathy, appendicitis, and herpes zoster infection. However, the myocarditis risk associated with SARS-CoV-2 infection was much higher (risk ratio, 18.28; 95% CI, 3.95 to 25.12), as was the risk for many other adverse events, the study found.
An accompanying editorial noted that the information on risk of myocarditis was only one of the important findings. “What is even more compelling about these data is the substantial protective effect of vaccines with respect to adverse events such as acute kidney injury, intracranial hemorrhage, and anemia, probably because infection was prevented,” it said.
Similarly, a British study published by The BMJ on Aug. 27 looked at clot risk among almost 30 million patients who received the Oxford-AstraZeneca or Pfizer-BioNTech vaccines and 1,758,095 COVID-19 patients. It found increased risk of thrombocytopenia and venous thromboembolism after receipt of the Oxford-AstraZeneca vaccine, but even higher risk of both after a positive COVID-19 test. Risk of arterial thromboembolism 15 to 21 days after Pfizer-BioNTech vaccination was 1.06 (95% CI, 1.01 to 1.10), while with infection it was 2.02 (95% CI, 1.82 to 2.24); that vaccine was not associated with thrombocytopenia or venous thromboembolism. Rates of cerebral venous sinus thrombosis (CVST) were increased in all three groups. “The small absolute risks associated with both of the vaccines should be noted; for instance, for 10 million people exposed to the ChAdOx1 nCoV-19 vaccine, there were seven excess events of CVST in the 28 days after the vaccine,” the authors wrote.
Three recent studies provided data on the delta variant of SARS-CoV-2. One, published in MMWR on Aug. 24, evaluated the protective effect of the vaccines. The analysis of U.S. health care workers had previously found that the mRNA vaccines were approximately 90% effective in preventing symptomatic and asymptomatic infection with SARS-CoV-2 before the delta variant appeared. Based on new data from when the delta variant was predominant (24,871 unvaccinated person-days with 19 infections and 119,218 vaccinated person-days with 24 infections), it found that vaccine effectiveness (VE) had dropped to 66% (95% CI, 26% to 84%). The authors warned that “this trend should be interpreted with caution because VE might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants.”
The second study, published in MMWR on Aug. 24, looked at 43,127 infections in Los Angeles in May to July 2021. About a quarter occurred in fully vaccinated patients, but they were significantly less likely to be hospitalized (3.2% vs. 7.6%), admitted to an ICU (0.5% vs. 1.5%), or placed on mechanical ventilation (0.2% vs. 0.5%) than unvaccinated patients. Based on 6,752 samples, the percentage of infections attributable to the delta variant increased over time among both the fully vaccinated (8.6% to 91.2%) and unvaccinated (8.2% to 87.1%). In May, there were differences in median cycle threshold (Ct) values, a surrogate indicator of viable and, hence, infectious, virus, by vaccination status, but by July, no differences were found. However, as of July 25, infection and hospitalization rates among unvaccinated persons were still 4.9 and 29.2 times, respectively, those in fully vaccinated people.
The third study, published by Clinical Infectious Diseases on Aug. 23, focused on COVID-19 illness severity. It compared 829 patients in Singapore hospitalized between December 2020 and May 2021 with 846 patients hospitalized between January 2020 and April 2020. The former group had a higher prevalence of the delta variant. Patients with the delta variant (n=157) had higher risk of oxygen requirement, ICU admission, or death (adjusted odds ratio, 4.90; 95% CI, 1.43 to 30.78). No differences were seen between the patients hospitalized in 2020 and the alpha and beta patients. Being vaccinated was associated with decreased illness severity. The delta variant was also associated with lower Ct and longer duration of a Ct value less than or equal to 30, which the authors noted “provides a potential mechanism for increased transmissibility.”
In other COVID-19 vaccine news, a study published by Annals of Internal Medicine on Aug. 31 showed the reduced effectiveness of the mRNA vaccines in people with chronic inflammatory disease (CID) treated with immunosuppressive medications. It found that 88.7% of 133 CID and 100% of 53 immunocompetent comparison participants developed antibodies after vaccination, although some CID patients developed numerically lower titers of anti-S IgG. Antibody titers after vaccination were lower in participants with CID receiving glucocorticoids or B-cell depletion therapy. The results reveal that “most patients with CID receiving immunosuppressive treatment were able to mount antibody responses, which provides justification for current recommendations for this population to be vaccinated,” said the authors.