Clinical and genetic risk factors for acute incident venous Thromboembolism in ambulatory patients with COVID-19.
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Author(s)
Type
Journal Article
Abstract
Importance: The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19-related VTE and relevant clinical and genetic risk factors remain to be elucidated. Objective: To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post-COVID-19 VTE. Design, Setting, and Participants: This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19-naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded. Exposures: First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia. Main Outcomes and Measures: The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models. Results: In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post-COVID-19 VTE. Conclusions and Relevance: In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.
Date Issued
2022-08-18
Date Acceptance
2022-07-13
Citation
JAMA Internal Medicine, 2022, 182 (10), pp.1063-1070
ISSN
2168-6106
Publisher
American Medical Association
Start Page
1063
End Page
1070
Journal / Book Title
JAMA Internal Medicine
Volume
182
Issue
10
Copyright Statement
© 2022 Xie J et al. JAMA Internal Medicine. This is an open access article distributed under the terms of the CC-BY License. This is an open access article distributed under the terms of the CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium. You are not required to obtain permission to reuse this article content, provided that you credit the author and journal.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35980616
PII: 2795466
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
COVID-19
Cohort Studies
Female
Fibrinolytic Agents
Humans
Male
Middle Aged
Obesity
Risk Factors
SARS-CoV-2
Thrombophilia
Venous Thromboembolism
Venous Thrombosis
Humans
Venous Thrombosis
Thrombophilia
Obesity
Fibrinolytic Agents
Risk Factors
Cohort Studies
Middle Aged
Female
Male
Venous Thromboembolism
COVID-19
SARS-CoV-2
1103 Clinical Sciences
1113 Opthalmology and Optometry
1117 Public Health and Health Services
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-08-18