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. 2022 Jan 12;17(1):e0261786.
doi: 10.1371/journal.pone.0261786. eCollection 2022.

COVID-19 is associated with higher risk of venous thrombosis, but not arterial thrombosis, compared with influenza: Insights from a large US cohort

Andrew Ward  1 , Ashish Sarraju  2 , Donghyun Lee  1 , Kanchan Bhasin  1 , Sanchit Gad  1 , Rob Beetel  1 , Stella Chang  3 , Mac Bonafede  3 , Fatima Rodriguez  2 , Rajesh Dash  1   2
Affiliations

COVID-19 is associated with higher risk of venous thrombosis, but not arterial thrombosis, compared with influenza: Insights from a large US cohort

Andrew Ward et al. PLoS One. .

Abstract

Introduction: Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort.

Methods: We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression.

Results: There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38-1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95-1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98-1.25) and MI (HR 0.93, 95% CI 0.85-1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19-1.56) and PE (HR 1.82, 95% CI 1.57-2.10) in patients with COVID-19.

Conclusion: In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.

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Conflict of interest statement

The authors have no interests to disclose with respect to this manuscript’s content. All listed authors made meaningful contributions to the manuscript and approved the final version. I have read the journal’s policy and the authors of have the following competing interests: AW, DL, KB, SG, and RB are paid employees of and report equity from HealthPals. SC and MB are paid employees and stockholders of Veradigm. FR reports equity from HealthPals and Carta; and consulting with Novartis, Janssen, and Novo Nordisk. Rajesh Dash reports equity from HealthPals, Heartbeam, and iMedrix; and consulting with Bayer and AstraZeneca. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Cohort selection diagram for the COVID-19 cohort (a) and for the influenza cohort (b). Abbreviations: ICD-10-CM—international classification of diseases, 10th revision; NAAT—nucleic acid amplification test.
Fig 2
Fig 2. Cumulative event rate curves for primary outcomes.
Stratified propensity weighted-cumulative event rate curves in the COVID-19 and influenza populations. Hazard ratios with 95% confidence intervals are shown. After weighting, cohorts were balanced across 49 covariates including demographics, medication use, and clinical comorbidities associated with arterial and venous thromboembolism.
Fig 3
Fig 3. Propensity-weighted cumulative event rate curves for secondary outcomes.
Hazard ratios with 95% confidence intervals are shown. After weighting, cohorts were balanced across 49 covariates including demographics, medication use, and clinical comorbidities associated with arterial and venous thromboembolism.
See this image and copyright information in PMC

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