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.

What is known

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  A systematic review of cohort studies suggested an incidence of CVT among hospitalised patients with COVID-19 to be about 800 per million patients. There was evidence of selection, ascertainment, and reporting bias in all included studies.

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  The incidence of CVT and PVT among both hospitalised and non-hospitalised patients with COVID-19 is unknown.

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  It is unknown if COVID-19 increases the risk of CVT and PVT.

What this study adds

Our study estimates that the absolute risk of CVT and PVT are respectively 42.8 and 392.3 per million patients (both hospitalised and non-hospitalised) in the 2 weeks after a diagnosis of COVID-19. COVID-19 increases the risk of CVT and PVT compared to patients diagnosed with influenza, and to people who have received a COVID-19 mRNA vaccine.