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Meta-Analysis
. 2021 Nov:138:104224.
doi: 10.1016/j.mvr.2021.104224. Epub 2021 Jul 15.

Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis

Andrianto  1 , Makhyan Jibril Al-Farabi  2 , Ricardo Adrian Nugraha  3 , Bagas Adhimurda Marsudi  4 , Yusuf Azmi  5
Affiliations
Meta-Analysis

Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis

Andrianto et al. Microvasc Res. 2021 Nov.

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 prognostic values of 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; I2:86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p < 0.001; I2:0%). 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; I2:80.4%], [SMD 0.55 [0.19-0.92], p = 0.003; I2:6.4%], [SMD 0.33 [0.04-0.62], p = 0.025; I2:7.9%], and [SMD 0.55 [0.10-0.99], p = 0.015; I2:23.6%], respectively).

Conclusion: The estimated pooled means show 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 outcomes in patients with COVID-19.

Prospero registration number: CRD42021228821.

Keywords: COVID-19; Endothelial dysfunction; Plasminogen activator inhibitor-1; Thrombomodulin; Tissue-type plasminogen activator; von Willebrand Factor.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA flowchart.
Fig. 2
Fig. 2
The estimated pooled mean for plasma levels of von Willebrand Factor antigen in patients with COVID-19. For individual studies, circle markers indicate study means and error bars indicate 95% confidence intervals. Markers are sized proportionately to the weight of the study in the analysis. Estimated pooled means for grouped studies are represented by the square markers.
Fig. 3
Fig. 3
Several biomarkers for endothelial dysfunction and the outcome of COVID-19. Patients presenting with a higher plasma levels of (A) von Willebrand Factor (VWF) antigen; (B) tissue-type plasminogen activator (t-PA); (C) plasminogen activator inhibitor-1 antigen (PAI-1) antigen; and (D) soluble thrombomodulin (sTM) have an increased risk of composite poor outcome.
Fig. 4
Fig. 4
Funnel-plot analysis for the analysis of the von Willebrand Factor (VWF) antigen. SMD, standardized mean difference.
See this image and copyright information in PMC

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