Bacterial and Viral Coinfections in Adult Patients Hospitalized With COVID-19 Throughout the Pandemic: A Multinational Cohort Study in the EuCARE Project

Background: Limited evidence exists on how the occurrence of bacterial and viral co-infections have developed since the SARS-CoV-2 Omicron variant emerged. We investigated whether the occurrence of community-onset co-infections in adult patients hospitalized with COVID-19 differed during the Wild type, Alpha, Delta, and Omicron periods, and whether such co-infections were associated with an increased risk of mortality. Methods: We conducted a multinational cohort study including COVID-19 hospitalizations until 30 April 2023 in five European countries. The outcome was bacterial and viral co-infections, based on five different test modalities. Variant periods were compared with regards to occurrences of co-infections and risk ratios for co-infections (Omicron versus pre-Omicron), as well as association with in-hospital mortality (Omicron versus pre-Omicron). Results: A total of 29,564 patients were included: 12,601 Wild type, 5,256 Alpha, 2,433 Delta, and 9,274 Omicron. The co-infection rate was 2.6% (327/12,601) for Wild type, 2.0% (105/5,256) for Alpha, 3.2% (77/2,433) for Delta, and 7.9% (737/9,274) for Omicron. Patients with Omicron had a significantly increased risk ratio of co-infection compared with preceding variants (1.88 [95% CI 1.53-2.32], P<0.001). These results were consistent across several subgroup analyses. An increased occurrence (19% [232/1,246] versus 11% [3,042/28,318]) and adjusted risk (1.69 [1.49-1.91], P<0.001) of in-hospital mortality was observed in patients with a verified co-infection compared with patients without a co-infection. Conclusions: Bacterial and viral co-infections were more prevalent during the Omicron period compared with preceding variants. Such co-infections were associated with an increased risk of in-hospital mortality, calling for sustained monitoring and clinical vigilance.