New research on booster doses, breakthrough infections, long-term COVID-19 symptoms

The effectiveness of a booster dose of the Pfizer-BioNTech vaccine against severe COVID-19 was described by an Israeli study published by The Lancet on Oct. 29. It followed (for a median of 13 days) 728,321 patients who received a booster and an equal number of matched controls who had gotten two doses at least five months earlier. At least seven days after the booster was given, its effectiveness was estimated to be 93% (95% CI, 88% to 97%; 231 vs. 29 events) against hospital admission, 92% (95% CI, 82% to 97%; 157 vs. 17 events) against severe disease, and 81% (95% CI, 59% to 97%; 44 vs. 7 events) against COVID-19-related death. The booster's effectiveness against hospitalization and severe disease didn't differ by sex or by age among those older than 40 years. The rate of severe outcomes in younger patients was too small to evaluate effect. Another study highlighted the need for boosters in immunocompromised patients, finding that the effectiveness of two shots of an mRNA vaccine was 77% versus 90% in immunocompetent patients, according to results published by MMWR on Nov. 2.

Breakthrough infections were the focus of several recent studies. Published Oct. 29 in MMWR, an analysis of patients hospitalized for COVID-19 found that they were much more likely to have had previous SARS-CoV-2 infection than to have been fully vaccinated with an mRNA vaccine (by a factor of 5.49), leading the authors to conclude that “all eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.” Among the fully vaccinated, however, previous SARS-CoV-2 infection was associated with lower risk of breakthrough infection and greater durability of antibodies, according to a study from Qatar and an analysis of health care workers in the U.S., respectively, both published by JAMA on Nov. 1. Two studies of hospitalized COVID-19 patients, one published by JAMA on Nov. 4 and one by Clinical Infectious Diseases on Nov. 2, looked at the characteristics of patients with breakthrough infections. An editorial accompanying the study in JAMA said its data were reassuring about the overall effectiveness of the vaccines but raised concerns about the effect waning over time and being lower in immunocompromised patients.

Persistent symptoms of COVID-19 were analyzed by a French study published by JAMA Internal Medicine on Nov. 8. It included 26,823 people who were tested for SARS-CoV-2 antibodies and asked if they had had COVID-19. Fewer than half of respondents with positive serology reported having had COVID-19, and about half of those who reported having had it actually had negative serology. Self-reported infection was positively associated with a variety of persistent physical symptoms, but a positive serology test was associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66 to 4.46). The results “suggest that physical symptoms persisting 10 to 12 months after the COVID-19 pandemic first wave may be associated more with the belief in having experienced COVID-19 infection than with actually being infected with the SARS-CoV-2 virus,” said the authors. “From a clinical perspective, patients in this situation should be offered a medical evaluation to prevent their symptoms being erroneously attributed to COVID-19 infection and to identify cognitive and behavioral mechanisms that may be targeted to relieve the symptoms.”

Finally, a trial of inhaled or intranasal ciclesonide in outpatients with COVID-19 did not find any significant benefit, according to results published by The BMJ on Nov. 2, and the NIH released an online tool to help people decide when to get tested for SARS-CoV-2.