Short-term and long-term stroke risk following SARS-CoV-2 infection in relation to disease severity: a Danish national cohort study

Objectives Studies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke in SARS-CoV-2 test-positive individuals compared with test-negative individuals stratified by disease severity during acute infection and post infection.Design A register-based cohort study.Setting A Danish nationwide study.Participants All Danish adults who had PCR tests for SARS-CoV-2 performed between 1 March 2020 and 30 November 2021. Test-positive individuals were included at their first positive test. For individuals tested prior to 30 November 2021, we randomly sampled an index date from the distribution of test dates among SARS-CoV-2 test-positive individuals. Test-positive individuals were followed during the acute phase of infection (days 0-14) and post infection (180 days after the acute phase). Test-negative individuals were followed in equivalent time periods.Primary and secondary outcome measures Incident ischaemic stroke risk in SARS-CoV-2 test-positive individuals compared with test-negative individuals during acute infection and post infection. We calculated subdistribution HRs (SHR) with death as a competing risk using propensity score weighting as confounder control. The risk was stratified according to disease severity: community managed, hospitalised, or admission to the intensive care unit.Results Among 3 910 219 SARS-CoV-2 PRC-tested individuals, 356 421 test-positive and 3 067 456 test-negative individuals were included. A positive SARS-CoV-2 test was associated with an SHR of 3.32 (95% CI 2.60 to 4.25) overall for stroke compared with test negative in the acute phase. In the postinfection period, the risk of stroke remained increased in individuals hospitalised during the acute phase (SHR 1.85, 95% CI 1.45 to 2.37). Individuals with community-managed SARS-CoV-2 had no increased long-term risk of stroke (SHR 1.01, 95% CI 0.88 to 1.16).Conclusion SARS-CoV-2 infection is associated with increased stroke risk. Disease severity seems to be an important factor. Individuals with community-managed SARS-CoV-2 had no increased stroke risk.