Prior antibiotic exposure is associated with worse outcomes in adults with COVID-19

Antibiotic-induced perturbations of the gut microbiome impair immunologic responses but whether they influence disease severity is unknown. The COVID-19 pandemic provided a unique opportunity to explore this question given widespread testing for SARS-CoV-2 infections.

To determine whether prior antibiotic exposure was associated with outcomes in patients with COVID-19.

Retrospective cohort study of all community-dwelling adults in Alberta, Canada with COVID-19 between March 2020 and June 2023. Subjects with antibiotic dispensations in the prior 3 months were compared (using multivariable logistic regression and propensity score (PS)-matching) to those without antibiotic exposure for differences in 30-day outcomes.

Of 445,646 adults with COVID-19, 49,581 (11.1%) were exposed to at least one antibiotic course in the prior 3 months. Those exposed to antibiotics were more likely to present to an emergency department (13.4% vs. 7.4%, aOR 1.52, 95%CI 1.48-1.57, PS-matched OR 1.48, 1.42-1.54), be hospitalised (5.8% vs. 2.8%, aOR 1.40,1.33-1.46, PS-matched OR 1.37, 1.29-1.45), or die (1.7% vs. 0.6%, aOR 1.28, 1.18-1.40, PS-matched OR 1.27, 1.14-1.42) than patients without prior antibiotic exposure. The associations were similar whether the antibiotic prescriptions were appropriate or not or whether antibiotic exposure periods were 6 weeks, 6 months, or 12 months prior to the positive RT-PCR test. The associations were stronger in those individuals with the highest tertile of antibiotic exposure, or those exposed to broad-spectrum antibiotics, or younger patients.

Prior antibiotic exposure is associated with worsened disease severity in patients infected with SARS-CoV-2. These findings support efforts to reduce antibiotic use.