Re-thinking all-cause COVID-19 hospitalizations as a surrogate measure for severe illness in observational surveillance studies.

All-cause COVID-19 hospitalization ≤ 30 days of infection is a common outcome for severe illness in observational/surveillance studies. Milder COVID-19 disease and COVID-19-specific measurements calls for an evaluation of this endpoint. This was a descriptive, retrospective cohort study of adults ≥ 18 who were established in primary care at Veteran Health Administration (VHA) facilities. The outcome was hospitalization within 30 days of a laboratory-confirmed, symptomatic SARS-CoV-2 infection. Between December 15, 2021 and May 1, 2022, a simple random sample of all VA facilities, excluding Puerto Rico or Philippines, was drawn to identify these hospitalized cases and determine whether hospitalization was due to COVID-19-specific causes. A chart review was conducted to record the inpatient clinical team's diagnosis and whether the inpatient team classified the diagnosis as COVID-19 related or not. These data were used to classify hospitalizations as either due to COVID-19-specific causes (direct manifestations of SARS-CoV-2 infection) or non-COVID-19-specific hospitalizations (incidental SARS-CoV-2 infection), A simple random sample of 9966 (12.3%) all-cause hospitalizations (95% CI: 12.1%, 12.5%) was used to select 300 representative patients. Of these, 226/300 (75.3%) were determined to be COVID-19-specific. COVID-19 pneumonia was most common (147/226, 65.0%). The highest proportion of COVID-19-specific hospitalizations occurred among unvaccinated (85.0%), followed by vaccinated but not boosted (73.7%) and boosted (59.4%) (p < 0.001). The proportion of non-COVID-19-specific hospitalizations was higher in the later period (15-30 days: 55.0%) than the early (0-15 days: 22.5%) (p = 0.003). This study supports the outcome of COVID-19-specific hospitalization instead of all-cause hospitalization in observational studies. The earlier outcome period (0-15 days) was less susceptible to potential measurement bias.

Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations.

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.