Concurrent Comparison of Severity of Influenza and Coronavirus Disease 2019 among Hospitalized Patients in Hong Kong: a Target Trial Emulation on Observational Health Care Data

OBJECTIVES:Influenza virus (IV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significant causes of hospitalization. Earlier studies showed more severe disease for SARS-CoV-2 infections, but many were compared with historical influenza cohorts and were conducted before the milder Omicron variant emerged. We aimed to compare the severity of SARS-CoV-2 infection with a concurrent cohort of IV infection among hospitalized patients after the emergence of the Omicron variant in Hong Kong SAR, China. METHODS:This is a target trial emulation study based on the public electronic health database in Hong Kong SAR, China. Adults aged ≥18 years who were hospitalized with laboratory-confirmed SARS-CoV-2 or IV infection between January 1, 2023, and January 31, 2024, were included. Pooled logistic regression was used to explore the risk of the composite outcome (30-day mortality, mechanical ventilation, intensive care unit [ICU] admission). RESULTS:A total of 47,956 cases were identified, including 32,523 SARS-CoV-2 mono-infections, 15,103 IV mono-infections, and 330 SARS-CoV-2/IV co-infections. Overall, the risks of composite outcome (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.06-1.23), 30-day mortality (HR, 1.20; 95% CI 1.09-1.32), and ICU admission (HR, 1.21; 95% CI 1.06-1.38) were higher for SARS-CoV-2 than IV infection. Subgroup analysis showed that male patients with SARS-CoV-2 were at higher risk of the composite outcome (HR, 1.19; 95% CI 1.08-1.31), 30-day mortality (HR, 1.26; 95% CI 1.11-1.44), and ICU admission (HR, 1.2; 95% CI 1.02-1.4) than male patients with IV. Post hoc analysis showed that SARS-CoV-2/IV co-infection was associated with an increased risk of 30-day mortality than SARS-CoV-2 mono-infection (HR, 2.11; 95% CI 1.58-2.81) or influenza mono-infection (HR, 3.45; 95% CI 2.19-5.42). CONCLUSION:SARS-CoV-2 Omicron infection was associated with more severe outcomes than IV mono-infection, and co-infection was more severe than mono-infection among hospitalized patients. Our findings have important implications for health care policies, including vaccine recommendations for SARS-CoV-2.