Cerebral venous thrombosis and portal vein thrombosis: a retrospective cohort study of 537,913 COVID-19 cases

Objectives: To estimate the absolute risk of cerebral venous thrombosis (CVT) and portal vein thrombosis (PVT) in the two weeks following a diagnosis of COVID-19, and to assess the relative risks (RR) compared to influenza or the administration of an mRNA vaccine against COVID-19. Design: Retrospective cohort study based on an electronic health records network Setting: Linked records between primary and secondary care centres within 59 healthcare organisations, primarily in the USA Participants: All patients with a confirmed diagnosis of COVID-19 between January 20, 2020 and March 25, 2021 were included (N=537,913, mean [SD] age: 46.2 [21.4] years; 54.9% females). Cohorts (matched for age, sex, and race) of participants diagnosed with influenza (N=392,424) or receiving the BNT162b2 or mRNA-1273 vaccine (N=366,869) were used for comparison. Main outcome measures: Diagnosis of CVT (ICD-10 code I67.6) or PVT (ICD-10 code I81) within 2 weeks after a diagnosis of COVID-19. Results: The incidence of CVT after COVID-19 diagnosis was 42.8 per million people (95% CI 28.5-64.2) including 35.3 per million (95% CI 22.6-55.2) first diagnoses. This was significantly higher than the CVT incidence in a matched cohort of patients with influenza (RR=3.83, 95% CI 1.56-9.41, P<0.001) and people who received an mRNA vaccine (RR=6.67, 95% CI 1.98-22.43, P<0.001). The incidence of PVT after COVID-19 diagnosis was 392.3 per million people (95% CI 342.8-448.9) including 175.0 per million (95% CI 143.0-214.1) first diagnoses. This was significantly higher than the PVT incidence in a matched cohort of patients with influenza (RR=1.39, 95% CI 1.06-1.83, P=0.02) and people who received an mRNA vaccine (RR=7.40, 95% CI 4.87-11.24, P<0.001). Mortality after CVT and PVT was 17.4% and 19.9% respectively. Conclusions: The incidence of CVT and PVT is significantly increased after COVID-19. The data highlight the risk of serious thrombotic events in COVID-19 and can help contextualize the risks and benefits of vaccination in this regard.