(112) Investigating Previous Antibiotic Exposure Patterns among COVID-19 Hospitalised Patients: An OpenSAFELY Matched Case-Control Study

Background: Repeated antibiotics might lead to adverse heath outcome due to increased chance to antibiotic resistance or altered gut microbiota. Several studies have observed altered gut microbiota and dysfunctional immune or metabolic responses related to severe COVID-19 infections in hospitalised patients.

Objectives: This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients.

Methods: With the approval of NHS England, the OpenSAFELY platform, integrated primary and secondary care, COVID-19 test, and death registration data, and covered 40% of the population in England. This matched case-control study included 3.16 million incident COVID-19 patients with at least two or more prior antibiotic prescriptions from February 2020 to December 2022. Patients who admitted to hospital for COVID-19 were defined as cases. Each case was matched with up to 6 controls of those without hospital admission or death records. Antibiotic exposures measured in prior 3 years of index date were categorised with 10 decile groups by random forest model. Patients within the same decile group share a similar antibiotic exposure history. A conditional logistic regression model was then used to evaluate the risk of COVID-19 hospitalisation among decile groups by adjusting confounders.

Results: Total prior number of antibiotic prescriptions, number of antibiotic types, number of broad-spectrum antibiotic prescriptions, time between (first to last antibiotics) and recent antibiotic use (at least six weeks before COVID-19 outcome) were associated with becoming a case. Antibiotic exposure characteristics were strongly associated with risk of severe COVID-19 outcome (adjusted odds ratio of 4.8 [95% confidence interval 4.6-5.0] compared highest decile of random forest score to lowest decile).

Conclusions: Our study provides evidence that antibiotic exposure time, frequency, diversity and broad-spectrum activity were associated with COVID-19 severity. There is an urgent need to review how antibiotic prescribing guidelines incorporate a risk-based approach to offset potential future of adverse consequences.