The short-, medium- and long-term risk and the multi-organ involvement of clinical sequelae after COVID-19 infection: a multinational network cohort study

Abstract

Objectives: To generate comprehensive evidence on the risk of clinical sequelae involving different organ systems over time after coronavirus disease 2019 (COVID-19) infection. Design: Multinational retrospective cohort study. Setting: Electronic medical records from the US, UK, France, Germany and Italy standardised to the Observational Medical Outcomes Partnership Common Data Model. Participants: A total of 303,251 individuals with a COVID-19 infection between 1 December 2019 and 1 December 2020 and propensity score matched non-COVID-19 comparators from 22,108,925 eligible candidates. Main outcome measures: Incidence of 73 clinical sequelae involving multiple organ systems including the respiratory, cardiovascular, dermatological and endocrine systems over the short- (0–6 months), medium- (6–12 months) and long-term (1–2 years) after COVID-19 infection. The hazard ratio (HR) and 95% confidence interval (95% CI) of individual disease outcomes were estimated using Cox proportional hazard regression. Results: Individuals with COVID-19 incurred a greater risk of clinical sequelae involving multiple organ systems including respiratory (France HR 2.23, 95%CI [2.10,2.37] to Italy 13.13 [11.80,14.63]), cardiovascular (Germany 1.39 [1.30,1.50] to US 1.79 [1.74,1.85]) and dermatological (UK 1.13 [1.01,1.25] to Italy 1.77 [1.42,2.21]) disorder over the short-term. While the risk of clinical sequelae has largely subsided during the medium-term, the risk of cardiovascular- (US 1.16 [1.11,1.21], France 1.10 [1.01,1.19]) and endocrine- (US 1.18 [1.12,1.24], Germany 1.15 [1.03,1.29]) related complications may continue to persist for up to two years. Conclusions: Through a network of multinational healthcare databases, this study generated comprehensive and robust evidence supporting the extensive multi-organ involvement of post-COVID-19 condition over the short-term period and the reduction in risk for most complications over the medium- and long-term.