Abstract
BACKGROUND: The mortality risk of co-infections/secondary infections (CoI/ScI) is under-reported in patients with non-critical COVID-19, leading to the under-management of CoI/ScI and publication bias in the medical literature. We aimed to investigate the association between CoI/ScI and mortality in patients hospitalised with mild-to-severe COVID-19. METHODS: We conducted a retrospective cohort study at a COVID-19 treatment hospital in Vietnam and collected all eligible medical records, with CoI/ScI status as the exposure (non-CoI/ScI and CoI/ScI, with the latter including nature of pathogen [bacterial, fungal, or bacterial + fungal] and multidrug-resistance pathogen [no MDRp or ≥ 1 MDRp]). The outcome was all-cause mortality, defined as in-hospital death by all causes or being discharged under critical illness. We used time-dependent analysis to report rates of mortality with 95% confidence intervals (95% CI, Poisson regression) and hazard ratios (HR) with 95% CI (Cox proportional hazards regression with Holm's method for multiplicity control). RESULTS: We followed 1466 patients (median age 61, 56.4% being female) for a median of 9 days. We recorded 387 (26.4%) deaths (95/144 [66.0%] in the CoI/ScI group and 292/1322 [22.1%] in the non-CoI/ScI group). Adjusted mortality rates (per 100 person-days) of the CoI/ScI (6.4, 95% CI 5.3 to 7.8), including bacterial (8.0, 95% CI 7.2 to 8.9), no MDRp (5.9, 95% CI 4.8 to 7.4), and ≥ 1 MDRp (9.0, 95% CI 8.2 to 10.0) groups were higher than that of the non-CoI/ScI group (2.0, 95% CI 1.8 to 2.2). These corresponded to higher risks of mortality in the overall CoI/ScI (HR 3.27, 95% CI 2.58 to 4.13, adjusted p < 0.001), bacterial CoI/ScI (HR 3.79, 95% CI 2.97 to 4.83, adjusted p < 0.001), no MDRp CoI/ScI (HR 3.13, 95% CI 2.42 to 4.05, adjusted p < 0.001), and ≥ 1 MDRp CoI/ScI group (HR 3.89, 95% CI 2.44 to 6.21, adjusted p < 0.001). We could not attain reliable estimates for fungal and bacterial + fungal CoI/ScI. CONCLUSION: Compared with the non-CoI/ScI group, patients with CoI/ScI had a significantly higher risk of all-cause mortality, regardless of resistance status. More evidence is needed to confirm the mortality risks in patients with fungal or bacterial + fungal CoI/ScI.