Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis

Abstract

Background: Studies have suggested that there is increased risk of thromboembolism (TE) associated with coronavirus disease 2019 (COVID-19). However, overall arterial and venous TE rates of COVID-19 and effect of TE on COVID-19 mortality is unknown. Methods: We did a systematic review and meta-analysis of studies evaluating TE in COVID-19. We searched PubMed, Cochrane, and Embase for studies published up to June 12, 2020. Random effects models were used to produce summary TE rates and odds ratios (OR) of mortality in COVID-19 patients with TE compared to those without TE. Heterogeneity was quantified with I 2. Findings: Of 425 studies identified, 42 studies enrolling 8271 patients were included in the meta-analysis. Overall venous TE rate was 21% (95% CI:17À26%): ICU, 31% (95% CI: 23À39%). Overall deep vein thrombosis rate was 20% (95% CI: 13À28%): ICU, 28% (95% CI: 16À41%); postmortem, 35% (95% CI:15À57%). Overall pulmonary embolism rate was 13% (95% CI: 11À16%): ICU, 19% (95% CI:14À25%); postmortem, 22% (95% CI:16À28%). Overall arterial TE rate was 2% (95% CI: 1À4%): ICU, 5% (95%CI: 3À7%). Pooled mortality rate among patients with TE was 23% (95%CI:14À32%) and 13% (95% CI:6À22%) among patients without TE. The pooled odds of mortality were 74% higher among patients who developed TE compared to those who did not (OR, 1.74; 95%CI, 1.01À2.98; P = 0.04). Interpretation: TE rates of COVID-19 are high and associated with higher risk of death. Robust evidence from ongoing clinical trials is needed to determine the impact of thromboprophylaxis on TE and mortality risk of COVID-19. Funding: None.

Significance of NETs Formation in COVID-19

“…Moreover, patients previously diagnosed with a thrombotic event showed significantly higher levels of calprotectin, a neutrophil activation marker [ 58 ]. A review and meta-analysis of the available literature on thromboembolism cases in COVID-19 patients unanimously indicates a high level of TE rates in these patients and a correlation with a high risk of death [ 59 ]. Jacqui Wise quotes Beverley Hunt (medical director of Thrombosis UK) “Thrombosis is definitely contributing to the high mortality rate from covid” and also mentions the lack of explicit recommendations for therapeutic management of thrombosis in COVID-19 patients, which is a serious medical problem [ 60 ].…”

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…Severe COVID-19 is associated with increased micro- and macrovascular thrombotic disease and pulmonary vascular histology shows severe endothelial cellular injury, microangiopathy with thrombosis, pulmonary capillary occlusion, and neoangenesis [ 69 , 70 ]. A recent investigation observed that the overall venous and arterial thromboembolism rate was 31% and 5% in ICU patients (95% CI: 23%–39% and 95% CI: 3%–7%, respectively) [ 71 ]. Pooled mortality among patients with vs. without thromboembolic events was 23% (95% CI: 14%–32%) vs. 13% (95% CI: 6%–22%) [ 71 ].…”

“…A recent investigation observed that the overall venous and arterial thromboembolism rate was 31% and 5% in ICU patients (95% CI: 23%–39% and 95% CI: 3%–7%, respectively) [ 71 ]. Pooled mortality among patients with vs. without thromboembolic events was 23% (95% CI: 14%–32%) vs. 13% (95% CI: 6%–22%) [ 71 ]. Although the exact underlying pathophysiology that leads to COVID-19-associated coagulopathy is not fully understood, it appears that endotheliopathy, vasoocclusion/stasis, and inflammation-associated activation of coagulation contribute to the respective complications [ [72] , [73] , [74] ].…”

Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis

“…The issue of hypercoagulabilityrelated thrombotic vascular events in those infected with SARS-CoV-2 is emerging 13,14 . Evidence suggests that COVID-19 patients may experience increased rates of thromboembolism, as high as 15%-26% 15 . In addition, another concern is the increased risk of a hemorrhagic stroke among COVID-19 patients [16][17][18] .…”