Association of COVID-19 with risks of all-cause and cause-specific mortality post-infection: A UK Biobank cohort study

BackgroundSARS-CoV-2 infection can lead to fatal multi-organ complications extending beyond the acute phase. However, a comprehensive assessment of relatively long-term mortality risks across various organ systems following COVID-19 is lacking. This study aimed to evaluate the impact of COVID-19 on all-cause and cause-specific mortality across a broad range of body systems and disease categories. MethodsThis prospective cohort study followed UK biobank (UKBB) participants (N=467,522; age: 50-87) from 31 Jan 2020 to 19 Dec 2022. COVID-19 exposure was classified as overall, hospitalized and non-hospitalized infections, with median follow-up durations of 274, 305 and 268 days, respectively. Prespecified outcomes included mortality from 12 organ systems and 47 individual diseases, categorized using the Clinical Classifications Software Refined (CCSR) system. Adjusted Cox models were used to assess mortality risks. Sensitivity analyses were conducted based on COVID-19 severity. Stratification by comorbidity and demographic variables were further performed. ResultsAll-cause mortality was significantly elevated across all COVID-19 exposure groups: overall (HR: 2.39, 95% CI: 2.29-2.50), hospitalized (HR: 6.29, 95% CI: 5.99-6.61), and non-hospitalized (HR: 1.23, 95% CI: 1.15-1.32). For cause-specific mortality, COVID-19 infection was associated with increased risks from circulatory (HR: 1.45, 95% CI: 1.26-1.66; subsequent values are presented in the same format), digestive (1.98, 1.45-2.70), genitourinary (2.54, 1.58-4.09), neurological (2.20, 1.85-2.62) and respiratory (1.39, 1.12-1.72) diseases, as well as external causes (3.42, 1.89-6.21) and neoplasms (1.53, 1.41-1.67). Hospitalized COVID-19 cases notably exhibited a greater proportion of outcomes with significantly elevated risks (11 out of 12 organ systems; 36 out of 42 individual diseases). Increased risks for external causes and neurological outcomes were also observed in non-hospitalized cases. Subgroup analyses revealed that advanced age, chronic kidney disease (CKD) and hypertension (HTN) exacerbated the risk of all-cause mortality following COVID-19, whereas atrial fibrillation (AF) was specifically associated with amplified respiratory and neurological mortality risks. ConclusionThis study demonstrates elevated risks of all-cause and cause-specific post-COVID mortality across multiple organ systems, with hospitalized cases exhibiting increased mortality risks across a broader spectrum of outcomes. These findings highlight the need for comprehensive strategies to mitigate COVID-19 severity and manage post-infection complications, particularly in survivors with older age and pre-existing high-risk comorbidities.