Association of COVID-19 with major arterial and venous thrombotic diseases: a population-wide cohort study of 48 million adults in England and Wales

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a pro-thrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear.

Methods: We studied vascular diseases after COVID-19 diagnoses in population-wide anonymised linked English and Welsh electronic health records from 1st January to 7th December 2020. We estimated adjusted hazard ratios (aHRs) comparing the incidence of arterial thromboses and venous thromboembolic (VTE) events after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics and prior history.

Results: Among 48 million adults, 125,985 were and 1,319,789 were not hospitalised within 28 days of COVID-19. In England, there were 260,279 first arterial thromboses and 59,421 first VTE events during 41.6 million person-years follow-up. aHRs for first arterial thrombosis compared with no COVID-19 declined from 21.7 (95% CI 21.0-22.4) in week 1 after COVID-19 to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE event declined from 33.2 (31.3-35.2) in week 1 to 1.80 (1.50-2.17) during weeks 27-49. aHRs were higher, for longer after diagnosis, after hospitalised versus non-hospitalised COVID-19, among people of Black and Asian versus White ethnicity and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTE events 49 weeks after COVID-19 were 2.5% and 0.6% respectively, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses.

Conclusion: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19. These results support policies to avoid severe COVID-19 with effective COVID-19 vaccines, early review after discharge, risk factor control and use of secondary preventive agents in high-risk patients.