Comorbidity patterns associated with severe COVID-19 outcomes: A cohort study based on the UK Biobank

Pre-existing comorbidities are linked to increased risk of severe COVID-19, but comprehensive assessments of comorbidity patterns remain limited.

We used network analysis to identify pre-existing comorbidity modules (i.e., groups of diseases more densely interconnected with each other than with other diseases in the comorbidity network) in a cohort of 420,920 individuals from the UK Biobank who were in England. We defined cases requiring hospitalization or who died of COVID-19 as "severe COVID-19". Logistic regression was used to examine associations between comorbidity modules and severe COVID-19, and a module-based comorbidity index was developed to predict severe COVID-19, compared with existing indices.

Comorbidity network analysis identified 190 disease pairs with confirmed comorbidity associations, which were further divided into seven comorbidity modules. Among the 30,914 individuals diagnosed with COVID-19, 3,970 were identified as severe cases (median age of 73.6 years, 58.77% being male). Six of seven identified modules showed statistically significant associations with severe COVID-19, especially modules related to circulatory and respiratory diseases (odds ratio = 1.67 [95% confidence interval 1.54-1.81]) and age-related eye diseases (1.39 [1.27-1.52]). Associations did not differ by sex, age or vaccination status but were generally stronger during the first wave of COVID-19 pandemic (i.e., 31st January-1st October, 2020). Our newly developed module-based comorbidity index showed better performance in predicting severe COVID-19 (AUC = 0.779) compared to the existing Charlson Comorbidity Index (0.714) and the 16-comorbidity index (0.714).

Our study demonstrated that pre-existing comorbidity modules, particularly modules related to circulatory and respiratory diseases and age-related eye diseases, were associated with severe COVID-19. Moreover, the module-based comorbidity index provides better prediction of severe COVID-19 than existing prediction indices.