Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales

Abstract

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

Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) 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 previous history.

Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses.

Conclusions: 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 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Keywords: COVID-19; electronic health records; myocardial infarction; pulmonary embolism; stroke; thrombosis; venous thrombosis.

Figure 1.

Age-, sex-, and region-adjusted and maximally adjusted hazard ratios (log scale) for different arterial thrombotic and venous thromboembolic and other vascular events by time since diagnosis of COVID-19. All results are maximally adjusted unless otherwise stated.

Figure 2.

Hazard ratios (log scale) for first arterial event after COVID-19 by time since diagnosis, overall and stratified by whether hospitalized with COVID-19, previous history of an arterial event, age, sex, and race. All results are maximally adjusted unless otherwise stated.

Figure 3.

Hazard ratios for first venous thromboembolism after COVID-19 by time since diagnosis, overall and stratified by whether hospitalized with COVID-19, previous history of a venous thromboembolism, age, sex, and race. All results are maximally adjusted unless otherwise stated.

Figure 4.

Estimated absolute increase in risk of arterial thrombosis and venous thromboembolism over time since diagnosis of COVID-19 compared with no COVID-19 diagnosis.