Clinical question: How frequent are breakthrough infections in health care workers fully vaccinated against COVID-19, and how does vaccination correlate with immune response and infectivity?
Background: While vaccines against COVID-19 are highly efficacious, a small percentage of breakthrough infections still occur. Vaccination appears to protect against severe disease. However, other characteristics of breakthrough infections are poorly understood.
Study design: Prospective cohort study.
Setting: Large medical center in Israel.
Synopsis: Fully vaccinated health care workers who either had symptoms or had a known COVID-19 exposure underwent extensive investigation, including epidemiologic investigations, SARS-CoV-2 testing through reverse transcription-polymerase chain reaction (RT-PCR), serologic assays, and genomic sequencing. The study investigators also obtained case-matched serum samples from vaccinated health care workers without symptoms or exposures, to compare vaccine-induced immune responses. Among an initial 11,453 fully vaccinated health care workers, 1,497 (13.1%) met inclusion criteria (symptomatic or exposed), and 39 breakthrough cases were identified (2.6% of the included population). In all cases, the suspected source was an unvaccinated person. While 26 (67%) of the infected workers developed symptoms, none required hospitalization. On follow-up, 19% of the infected workers had residual symptoms six weeks after diagnosis. No cases of transmission from infected health care workers (secondary infections) were identified, including household contacts. However, N-gene levels indicated likely infectivity and all healthcare workers followed isolation protocols after being notified of positive results. Infected health care workers with available pre-infection serologies had a significantly lower level of neutralizing antibodies pre-infection than did uninfected controls.
Bottom line: In health care workers, COVID-19 vaccination reduces the risk of infection and prevents severe infection, but still may be associated with long-COVID-19 symptoms. This study also demonstrates a correlation between lower levels of neutralizing antibodies and breakthrough infections.
Citation: Berg M et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med 2021;385:1474-84.
Dr. Bonsall is an associate professor of medicine at Emory University School of Medicine in the division of hospital medicine. She is the chief of hospital medicine at Grady Memorial Hospital, Atlanta.