Age is the Main Determinant of COVID-19 Related in-Hospital Mortality with Minimal Impact of Pre-Existing Comorbidities: A Retrospective Cohort Study.

Abstract

Abstract Background: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods: In this multicenter retrospective cohort study of 45 Dutch hospitals, 4,806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69 [58-77] years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with in-hospital mortality. The effect of comorbidities on the relation of age with in-hospital mortality was evaluated using mediation analysis. Results: In-hospital COVID-19 related mortality occurred in 1,108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively; both p<0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. Conclusions: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration: CAPACITY-COVID (NCT04325412).