Evaluating Severe COVID-19 Incidence After Initial, Booster Vaccination


Data from periods of Delta and Omicron variant predominance were evaluated in a retrospective cohort study.

Among adults who were fully vaccinated and boosted against COVID-19, there was a low incidence of either hospitalization with COVID-19 pneumonia or death during periods with high circulation of Delta and Omicron SARS-CoV-2 variants, according to research results published in JAMA.1

Through a retrospective cohort study, researchers used data from a large cohort of adults who received care at a United States Veterans Health Administration (VHA) facility to evaluate the incidence of breakthrough infection or severe illness after initial vaccination and booster vaccination with either BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S vaccines (Janssen/Johnson & Johnson).

The primary study outcomes included symptomatic breakthrough COVID-19 infection, hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death.

The cohort included 1,610,719 participants (68.4% aged 65 years or older; 8.2% women), of whom 70.4% had high-risk comorbid conditions and 9.9% had immunocompromising conditions. Within this group, 95.9% received their initial vaccine series between December 2020 and April 2021; 61.8% received boosters between July 1 and November 30, 2021, while the remaining 38.2% received boosters after December 1, 2021. More than 90% of patients received the same type of mRNA vaccine for their initial vaccine series and their booster shot.

Over the course of a 24-week follow-up period, 20,138 participants were diagnosed with breakthrough COVID-19 (125 events per 10,000 persons). A total of 1435 participants were hospitalized with COVID-19 pneumonia or died (8.9 events per 10,000 persons), and 541 participants were hospitalized with severe pneumonia or died (3.4 events per 10,000 persons). Cumulative incidence estimates were, according to the researchers, “similar regardless of vaccination and booster combination.”

Within the group of 122,028 participants who were boosted and who had an average COVID-19 risk, 1701 had breakthrough COVID-19, 11 had COVID-19 pneumonia or died, and 4 developed severe COVID-19 pneumonia or died (140, 0.9, and 0.3 events per 10,000 persons).

Within a subgroup of patients considered high-risk, the cumulative incidence of hospitalization with pneumonia or death of 24 weeks was 9.6 per 10,000 persons. Hospitalization incidence was 1.9 per 10,000 persons; among those with high-risk comorbid conditions, incidence rates were 6.7 and 39.6 per 10,000 persons, respectively. When compared with the subgroup of adults age 65 and older without high risk conditions, the cumulative incidence ratio of hospitalization with pneumonia or death was larger in those with immunocompromising conditions.

Study limitations include the inability to measure potential confounders, including COVID-19 exposure behavior, the exclusion of nursing home residents to allow for greater generalizability of results to “community-dwelling individuals,” and the high number of white men relative to other genders and races within the study cohort.

“In this national US cohort of adults receiving care at VHA facilities, the overall risk of hospitalization with COVID-19 pneumonia or death was low across vaccine and booster types,” the investigators concluded. “The 24-week observation period occurred while a series of SARS-CoV-2 variants were predominant in the US…suggesting that boosters continued to provide protection against severe illness despite viral evolution.”

Disclosure: One study author reported receipt of grants from Merck, Gilead, and Lilly. No other researchers had conflicts of interest to disclose.


  1. Kelly JD, Leonard S, Hoggatt KJ, et al. Incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1283, and Ad26.COV2.S vaccines. JAMA. Published online September 26, 2022. Doi:10.1001/jama.2022.17985
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