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. 2020 Aug 3;130(8):3950-3953.
doi: 10.1172/JCI140183.

COVID-19, microangiopathy, hemostatic activation, and complement

Wen-Chao Song  1   2 , Garret A FitzGerald  1   2   3
Affiliations

COVID-19, microangiopathy, hemostatic activation, and complement

Wen-Chao Song et al. J Clin Invest. .
No abstract available

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Conflict of interest statement

Conflict of interest: Conflict of interest WCS owns equity in, receives consultant fees and research grants from, and is an inventor on patents for anti-complement mAbs (WO2018/165062, WO2018/148486, and US2020/0148754A1) and gene therapy (WO2017/053732A2), licensed to Kira Pharmaceuticals and Aevitas Therapeutics. GAF is an advisor to Calico Laboratories, from which he receives salary and research support.

Figures

Figure 1
Figure 1. Potential mechanisms of complement-mediated pathology in COVID-19.
SARS–CoV-2 virus may directly activate the complement pathways. Damaged host tissues could also secondarily activate complement via any of the three pathways: the classical pathway, the lectin pathway, or the alternative pathway. Complement activation generates the anaphylatoxins C3a and C5a and the MAC C5ab-9. The C5a anaphylatoxin can cause neutrophil and monocyte activation, promote the formation of NET and platelet-leukocyte aggregates, and stimulate neutrophil degranulation and the release of tissue factor to trigger the extrinsic coagulation pathway. These C5a effects may contribute to a hypercoagulative state leading to VTEs and disseminated intravascular coagulation (DIC). The MAC C5b-9 can cause direct endothelial injury and platelet activation, leading to TMA. Capillary and blood vessel occlusion by TMA and VTEs eventually results in tissue ischemia and oxidant injury, contributing to multiorgan failure in COVID-19. AKI, acute kidney injury; FB, complement factor B; FD, complement factor D; P, properdin.
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