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. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by Woodard in this issue.

Graphical abstract

Figure 1:

Flowchart of the literature review process. COVID-19 = coronavirus disease 2019, PCR = polymerase chain reaction.

Figure 2a:

Forest plots show pooled incidence rates of (a) pulmonary embolism (PE) (n = 22) and (b) deep vein thrombosis (DVT) (n = 18) in patients with coronavirus disease 2019. The estimated overall incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9) and 14.8% (95% CI: 8.5, 24.5), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects. Forest plots show pooled incidence rates of (c, d) both pulmonary embolism (PE) and deep vein thrombosis (DVT) (n = 13) in patients with coronavirus disease 2019. In the 13 studies that reported both PE and DVT, the incidence rates were 10.3% (95% CI: 5.7, 17.8) and 12.0% (95% CI: 5.9, 22.7), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects.

Figure 2b:

Forest plots show pooled incidence rates of (a) pulmonary embolism (PE) (n = 22) and (b) deep vein thrombosis (DVT) (n = 18) in patients with coronavirus disease 2019. The estimated overall incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9) and 14.8% (95% CI: 8.5, 24.5), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects. Forest plots show pooled incidence rates of (c, d) both pulmonary embolism (PE) and deep vein thrombosis (DVT) (n = 13) in patients with coronavirus disease 2019. In the 13 studies that reported both PE and DVT, the incidence rates were 10.3% (95% CI: 5.7, 17.8) and 12.0% (95% CI: 5.9, 22.7), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects.

Figure 2c:

Forest plots show pooled incidence rates of (a) pulmonary embolism (PE) (n = 22) and (b) deep vein thrombosis (DVT) (n = 18) in patients with coronavirus disease 2019. The estimated overall incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9) and 14.8% (95% CI: 8.5, 24.5), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects. Forest plots show pooled incidence rates of (c, d) both pulmonary embolism (PE) and deep vein thrombosis (DVT) (n = 13) in patients with coronavirus disease 2019. In the 13 studies that reported both PE and DVT, the incidence rates were 10.3% (95% CI: 5.7, 17.8) and 12.0% (95% CI: 5.9, 22.7), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects.

Figure 2d:

Forest plots show pooled incidence rates of (a) pulmonary embolism (PE) (n = 22) and (b) deep vein thrombosis (DVT) (n = 18) in patients with coronavirus disease 2019. The estimated overall incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9) and 14.8% (95% CI: 8.5, 24.5), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects. Forest plots show pooled incidence rates of (c, d) both pulmonary embolism (PE) and deep vein thrombosis (DVT) (n = 13) in patients with coronavirus disease 2019. In the 13 studies that reported both PE and DVT, the incidence rates were 10.3% (95% CI: 5.7, 17.8) and 12.0% (95% CI: 5.9, 22.7), respectively. Significant interstudy heterogeneity was seen in all groups. CTPA = CT pulmonary angiography, ICU = intensive care unit, RE = random effects.

Figure 3:

Summary receiver operating characteristic curve shows the diagnostic performance of D-dimer tests for pulmonary embolism in patients with coronavirus disease 2019. Dots of different colors indicate separate data of 11 studies.

Figure 4a:

Funnel plots used to detect publication bias. Each circle represents a study included in the analysis. Probability values of asymmetry from the Egger test are shown. (a) Incidence of pulmonary embolism (PE). (b) Incidence of deep vein thrombosis (DVT).

Figure 4b:

Funnel plots used to detect publication bias. Each circle represents a study included in the analysis. Probability values of asymmetry from the Egger test are shown. (a) Incidence of pulmonary embolism (PE). (b) Incidence of deep vein thrombosis (DVT).