Effect modification of the association between comorbidities and severe course of COVID-19 disease by age of study participants: a systematic review and meta-analysis

Background Comprehensive evidence synthesis on the associations between comorbidities and behavioural factors with hospitalisation, intensive care unit (ICU) admission, and death due to COVID-19 is required for deriving national and international recommendations on primary targets for non-pharmacological interventions (NPI) and vaccination strategies. Methods We performed a rapid systematic review and meta-analysis on studies and publicly accessible data to quantify associations between predisposing health conditions, demographics, behavioural factors on the one hand and hospitalisation, ICU admission, and death from COVID-19 on the other hand. We provide ranges of reported and calculated effect estimates and pooled relative risks derived from a meta-analysis and meta-regression. Results Seventy-five studies were included in qualitative and 74 in quantitative synthesis, with study populations ranging from 19 to 44,672 COVID-19 cases. The risk of dying from COVID-19 was significantly associated with cerebrovascular [pooled relative risk (RR) 2.7 (95% CI 1.7–4.1)] and cardiovascular [RR 3.2 (CI 2.3–4.5)] diseases, hypertension [RR 2.6 (CI 2.0–3.4)], and renal disease [RR 2.5 (CI 1.8–3.4)], with high heterogeneity in pooled estimates, partly but not solely explained by age of study participants. For some comorbidities, our meta-regression showed a decrease in effect on the severity of disease with a higher median age of the study population. Compared to death, associations between several comorbidities and hospitalisation and ICU admission were less pronounced. Conclusions We obtained robust estimates on the magnitude of risk for COVID-19 hospitalisation, ICU admission, and death associated with comorbidities, demographic, and behavioural risk factors and show that these estimates are modified by age of study participants. This interaction is an important finding to be kept in mind for current vaccination strategies and for the protection of individuals with high risk for a severe COVID-19 course.