Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis
Abstract
Background
Several studies have reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect endothelial cells, and endothelial dysfunction is often found in severe cases of coronavirus disease 2019 (COVID-19). To better understand the pathological mechanisms underlying endothelial dysfunction in COVID-19-associated coagulopathy, we conducted a systematic review and meta-analysis to assess biomarkers of endothelial cells in patients with COVID-19.
Methods
A literature search was conducted on online databases for observational studies evaluating biomarkers of endothelial dysfunction and composite poor outcomes in COVID-19 patients.
Results
A total of 1187 patients from 17 studies were included in this analysis. The estimated pooled means for von Willebrand Factor (VWF) antigen levels in COVID-19 patients was higher compared to healthy control (306.42 [95% confidence interval (CI) 291.37-321.48], p<0.001; I 2 :86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p<0.001; I 2 :0%). Meta-analysis showed that higher plasma levels of VWF antigen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) antigen, and soluble thrombomodulin (sTM) were associated with composite poor outcome in COVID-19 patients ([standardized mean difference (SMD) 0.74 [0.33-1.16], p<0.001; I 2 :80.4%], [SMD 0.55 [0.19-0.92], p=0.003; I 2 :6.4%], [SMD 0.33 [0.04-0.62], p=0.025; I 2 :7.9%], and [SMD 0.55 [0.10-0.99], p=0.015; I 2 :23.6%], respectively).
Conclusion
The estimated pooled means shows increased levels of VWF antigen in COVID-19 patients. Several biomarkers of endothelial dysfunction, including VFW antigen, t-PA, PAI-1, and sTM, are significantly associated with increased composite poor outcome in patients with COVID-19.
PROSPERO registration number
CRD42021228821
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