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

## TL;DR

This study suggests that using all-cause hospitalizations for severe COVID-19 may be misleading and recommends focusing on hospitalizations directly caused by the virus.

## Contribution

The study introduces a method to distinguish between hospitalizations directly caused by SARS-CoV-2 and those coinciding with infection.

## Key findings

- 75.3% of all-cause hospitalizations were due to direct SARS-CoV-2 effects.
- Unvaccinated individuals had the highest rate of direct SARS-CoV-2 hospitalizations.
- Non-COVID-19 hospitalizations increased in the later period (15–30 days) after infection.

## Abstract

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.