PDF icon Download PDF
Open Access
CC BY-NC-ND 4.0 · Thromb Haemost 2024; 124(08): 709-720
DOI: 10.1055/a-2263-8514
Coagulation and Fibrinolysis

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study

Zhengran Li‡   *
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
4   Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
,
Minghui Zeng‡   *
2   Institute of Scientific Research, Southern Medical University, Guangzhou, China
,
Tong Wu
3   The First Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Zijin Wang
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Yuxin Sun
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Ziran Zhang
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Fanye Wu
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Zejun Chen
1   The Second Clinical Medicine School, Southern Medical University, Guangzhou, Guangdong, China
,
Min Fu 
4   Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
,
Fanke Meng
5   Emergency Department, Zhujiang Hospital of Southern Medical University, Guangzhou, China
› Author Affiliations
› Further Information
  Permissions and Reprints


Preview

Abstract

Background Coronavirus disease 2019 (COVID-19) and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers.

Methods We used two-sample Mendelian randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods. All the results were examined by false discovery rate (FDR) with the Benjamin and Hochberg method for this correction to minimize false positives. We used R language for the analysis.

Results All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (odds ratio [OR] = 0.639, 95% confidence interval [CI]: 0.435–0.938) and IL-1R1 (OR = 0.603, 95% CI = 0.417–0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 and increased C–C motif chemokine 3. Hospitalized COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had higher mean platelet volume (MPV) and lower platelet count. These changes in TFPI, tPA, IL-1R1, MPV, and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis.

Conclusion TFPI, IL-1R, and seven other indicators provide causal clues of the pathogenesis of COVID-19 and thrombosis. This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level.

Keywords

COVID-19 - Mendelian randomization - thrombosis - TFPI - IL-1R

Data Availability Statement

The data generated and codes used in the current study are available in this published article and [Supplementary File] (available in the online version) associated with it. The data underlying this article are available in IEU OpenGWAS project, at https://gwas.mrcieu.ac.uk/.


Ethical Approval Statement

The data for this study came from a public database, so no such approval was required.


Authors' Contribution

M.Z. collected and organized the data. Z.L. analyzed the data and finished the writing. All authors participated in the writing and review of the article.


* These authors contributed equally to the research.


Supplementary Material



Publication History

Received: 19 July 2023

Accepted: 17 November 2023

Accepted Manuscript online:
07 February 2024

Article published online:
05 March 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

Comment to this article:

Tissue Factor Pathway Inhibitor and Interleukin-1 Receptor Levels in COVID-19Thromb Haemost 2024; 124(08): 721-724
DOI: 10.1055/a-2315-8278