Association of COVID-19 with risks of hospitalization and mortality from other disorders post-infection: A study of the UK Biobank

ObjectiveTo study whether COVID-19 infection may be associated with increased hospitalization and mortality from other diseases. DesignCohort study. SettingThe UK Biobank. ParticipantsAll subjects in the UK Biobank with available hospitalization records and alive as of 31-Jan-2020 (N= 412,096; age 50-87). Main outcome measuresWe investigated associations of COVID-19 with hospitalization and mortality due to different diseases post-infection. We conducted a comprehensive survey on disorders from all systems (up to 135 disease categories). Multivariable Cox and Poisson regression was conducted controlling for main confounders. For sensitivity analysis, we also conducted separate analysis for new-onset and recurrent cases, and other analysis such as the prior event rate adjustment(PERR) approach to minimize effects of unmeasured confounders. We also performed association analyses stratified by vaccination status. Time-dependent effects on subsequent hospitalization and mortality were also tested. ResultsCompared to individuals with no known history of COVID-19, those with severe COVID-19 (requiring hospitalization) exhibited higher hazards of hospitalization and/or mortality due to multiple disorders (median follow-up=608 days), including disorders of respiratory, cardiovascular, neurological, gastrointestinal, genitourinary and musculoskeletal systems. Increased hazards of hospitalizations and/or mortality were also observed for injuries due to fractures, various infections and other non-specific symptoms. These results remained largely consistent after sensitivity analyses. Severe COVID-19 was also associated with increased all-cause mortality (HR=14.700, 95% CI: 13.835-15.619). Mild (non-hospitalized) COVID-19 was associated with modestly increased risk of all-cause mortality (HR=1.237, 95% CI 1.037-1.476) and mortality from neurocognitive disorders, as well as hospital admission from a few disorders such as aspiration pneumonitis, musculoskeletal pain and other general signs/symptoms. All-cause mortalities and hospitalizations from other disorders post-infection were generally higher in the pre-vaccination era. The deleterious effect of COVID-19 was observed to wane over time, with maximum HR in the initial phase. ConclusionsIn conclusion, this study revealed increased risk of hospitalization and mortality from a wide variety of pulmonary and extra-pulmonary diseases after COVID-19, especially for severe infections. Mild disease was also associated with increased all-cause mortality. Causality however cannot be established due to observational nature of the study. Further studies are required to replicate our findings.