A systematic review and meta-analysis of incidence, prognosis, and laboratory indicators of venous thromboembolism in hospitalized patients with coronavirus disease 2019

Abstract

Objective: We have summarized the incidence, anticoagulation panels, laboratory characteristics, and mortality of venous thromboembolism (VTE) in hospitalized patients with coronavirus disease 2019 .Methods: After systematically searching PubMed, Embase, the Cochrane Library, MedRxiv, and BioRxiv, a systematic review and meta-analysis of 18 retrospective, 6 prospective observational, and 2 cross-sectional studies was performed according to the guidelines of the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement.Results: Overall, 4382 hospitalized patients with COVID-19 were included. Men accounted for significantly more patients than did women (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.25-2.02; P < .001). The total incidence of VTE among the patients with COVID-19 was 28.3% (95% CI, 21.6%-35.4%), with an incidence of 38.0% (95% CI, 29.1%-47.4%) and 17.2% (95% CI, 11.4%-23.8%) among those with severe and general COVID-19, respectively. The total incidence of deep vein thrombosis (DVT) of the lower extremities was 18.3% (95% CI, 10.8%-27.2%). The incidence of DVT was 22.1% (95% CI, 11.0%-35.5%) and 12.8% (95% CI, 5.0%-23.3%) in those with severe and general COVID-19, respectively. The total incidence of pulmonary embolism was 17.6% (95% CI, 12.3%-23.5%), with a rate of 21.7% (95% CI, 14.8%-29.3%) in severe cases and 12.5% (95% CI, 6.1%-23.5%) in general cases. When COVID-19 severity was unclassified, the mortality for the patients with VTE was not significantly greater (25.2%; 95% CI, 12.2%-40.5%) than that for those without VTE (10.2%; 95% CI, 3.4%-19.5%; OR, 1.88; 95% CI, 0.46-7.64; P ¼ .377). However, among the patients with severe COVID-19, those who had developed VTE had significantly greater mortality compared with those without VTE (OR, 2.02; 95% CI, 1.15-3.53; P ¼ .014). The patients with COVID-19 and VTE had significantly higher D-dimer levels than did similar patients without VTE in multiple studies. Conclusions:The occurrence of VTE, DVT, and pulmonary embolism has been substantial among hospitalized patients with COVID-19, especially among those with severe COVID-19. Patients with severe COVID-19 and VTE had significantly greater mortality compared with similar patients without VTE. An increased D-dimer level might be an indicator of the occurrence of VTE in patients with COVID-19.

Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study

“…We found that male gender was significantly associated with PE, in line with previous reports. ( 7 , 13 , 14 ) A similar sex-bias was previously reported in COVID-19 and other infectious diseases. In a metaanalysis including over three million reported global COVID-19 cases, men were almost three times more likely to require intensive treatment unit and had 40% higher odds of death than women.…”

“…Our 25% incidence of PE in all hospitalized patients with COVID-19 is higher than the 17.6% (95% CI: 12.3% - 23.5%) overall PE incidence, and closer to 21.7% (95%CI:14.8% - 29.3%) incidence in the severe group, reported by Liu et al in a systematic review and meta-analysis. ( 7 ) We also did not find significantly higher PE incidence in ICU patients. This might reflect that hospitalized patients in our multicentric cohort were all on the severe end of the spectrum.…”

“…( 15 ) While the effects of androgen on the endothelial functioning was also suspected as a contributing factor, making the male gender a potential risk factor for VTE, more so in the context of COVID-19. ( 7 )…”

“…D-dimer measures fibrin break down products and has been utilized for prediction and prognosis of venous thromboembolism among patients with COVID-19. (7,9,(17)(18)(19)(20)(21) One study showed d-dimer peaks as the measurements approached the day of ultrasound examination for DVT, following an inverse-U shape. (19) It is thought that the sensitivity of d-dimer for diagnosis of VTE diminishes with time.…”

“…not ICU admitted) disease (21.7% vs 12.5%). ( 7 ) Thus, the incidence of PE varies widely in the literature and there remains uncertainty about who should be imaged. A high prevalence of right heart strain has also been noted ( 8 ) raising the possibility that PE may be more lethal in patients with COVID-19; yet the risk factors for PE in COVID-19 are not well established.…”