Pulmonary Embolism and Deep Vein Thrombosis in COVID-19: A Systematic Review and Meta-Analysis

Abstract

Background

The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown.

Purpose

To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data.

Materials and Methods

A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve.

Results

Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I² = 0.93) and 14.8% (95% CI: 8.5, 24.5; I² = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively).

Conclusion

Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19.

Summary:

This article aimed to look at the association between Covid-19 and DVT/PE, as well as the association between DVT and PE in these patients. It also aimed to look at the accuracy of the D-dimer test, specifically in this population of patients. This meta-analysis looked at 27 studies with a total of 3342 patients with COVID-19, and found an incidence rate of 16.5% for PE and 14.8% for DVT. It also found that DVT was present in 42.4% of patients who had PE (so greater than half of the patients who had PE did not have DVT- usually 60%). Actual incidence is unknown because reported incidence ranged from .7% to 57.0% amongst the various studies.

Studies with anticoagulation had lower rate of DVT/PE, studies with patients in ICU, increased severity of disease, and those who had CTPA had significantly higher rates of DVT/PE than those not admitted to ICU (exceeded 20% incidence in those in ICU). PE was confined to the peripheral pulmonary arteries in more than half of the patients with PE.

A concern about D- dimer levels was that they tend to be elevated in patients with COVID even without having a PE. However, D dimer levels of 500 and 1000 ug/L showed high sensitivity but very low specificity for PE/DVT. These are similar guidelines and cutoffs as pre-existing guidelines, and can be used as a basis for further screening for PE such as CTPA. However, since specificity is low, D-dimer level cannot effectively be used to rule out PE. A combination of pretest clinical probability assessment with age-adjusted D-dimer levels could help improve the diagnostic effect of D-dimer levels.

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