CDC and FDA weigh in on safety of bivalent vaccine; research examines COVID-19 sequelae, omicron variants

The CDC and FDA said an observed association of ischemic stroke with the Pfizer-BioNTech bivalent booster is very unlikely to represent a true clinical risk. New studies reported on symptoms a year after mild COVID-19 and estimated protection against the omicron variants.

The CDC and FDA recently provided information and reassurance about a possible link between the bivalent Pfizer-BioNTech COVID-19 vaccine and ischemic strokes in people ages 65 years and older. According to a Jan. 13 announcement, the CDC's near-real-time surveillance system, Vaccine Safety Datalink (VSD), identified a signal that met the statistical criteria to prompt investigation into rates of ischemic stroke in this age group in the 21 days after receipt of the vaccine. The agencies noted that no other safety systems have shown a similar signal and that multiple subsequent analyses—using data from CMS, Veterans Affairs, the Vaccine Adverse Event Reporting System, and the manufacturer—have not found an association. The agencies will continue to monitor the data but said that “it is very unlikely that the signal in VSD represents a true clinical risk” and they are not recommending any change in vaccination practice. The signal was not identified with the bivalent Moderna vaccine.

Patients with mild cases of COVID-19 often had lingering symptoms but they commonly resolved by one year, according to a study published by The BMJ on Jan. 11. Researchers looked through almost 2 million patient records in Israel to compare rates of 70 reported long-term outcomes among patients with and without COVID-19 vaccination or infection. Anosmia and dysgeusia were significantly associated, both soon after infection (30 to 180 days) and later (180 to 360 days), with hazard ratios (HRs) of 4.59 (95% CI, 3.63 to 5.80) and 2.96 (95% CI, 2.29 to 3.82), respectively. Other symptoms found at elevated rates in both time periods included cognitive impairment (HRs, 1.85 [95% CI, 1.58 to 2.17] and 1.69 [95% CI, 1.45 to 1.96]), dyspnea (HRs, 1.79 [95% CI, 1.68 to 1.90] and 1.30 [95% CI, 1.22 to 1.38]), weakness (HRs, 1.78 [95% CI, 1.69 to 1.88] and 1.30 [95% CI, 1.22 to 1.37]), and palpitations (HRs, 1.49 [95% CI, 1.35 to 1.64] and 1.16 [95% CI, 1.05 to 1.27]). Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the first 180 days. Vaccinated patients had a lower risk for dyspnea after infection than unvaccinated patients. “This nationwide dataset of patients with mild covid-19 suggests that mild disease does not lead to serious or chronic long term morbidity in the vast majority of patients and adds a small continuous burden on healthcare providers,” the study authors concluded.

Several recent publications analyzed the omicron variants. Results of Pfizer-BioNTech's phase 3 trial of its bivalent vaccine were published by the New England Journal of Medicine (NEJM) on Jan. 19. A total of 1,846 adults ages 55 years and older (all of whom had received three doses of the original vaccine) were randomized to another dose of the vaccine or one of the monovalent or bivalent vaccines updated for omicron. The updated vaccines had a safety profile similar to the original, induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains, the trial found. One letter to NEJM used antibody titers from vaccinated U.S. patients to determine that the BQ.1.1 and XBB.1 variants escaped neutralizing antibodies substantially more effectively than the BA.5 variant, while another compared cases and controls in Qatar and found that the effectiveness of previous infection against reinfection with BA.2.75.2 appears to be lower than that against BA.4 or BA.5 re-infection.

A systematic review, published by The Lancet Infectious Diseases on Jan. 18, found 153 different estimates of the protective effect of vaccination and past infection against future COVID-19 infection and hospitalization, with about half having serious risk of bias.