We have read with great interest the article by King et al.1 recently published in Revista Española de Cardiología. In this article, the authors discuss the higher incidence of thrombotic events in multiple territories and a higher International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the authors mention that they have not ruled out a pre-existing prothrombotic state, our group, consistent with what the authors described,2 has proposed a possible role of endothelial injury, complement, and coagulation in the pathogenesis of coronavirus disease 2019 (COVID-19).3
Our pathogenic scheme is based on the similarity of certain clinical and histopathologic findings of various entities that have thrombotic microangiopathy in common with COVID-19, and it postulates that the damage induced by this disease has an endothelial origin with 2 pathogenic routes: an inflammatory route, with predominance of the “cytokine storm” component, and a microangiopathic route involving the complement system.3
Furthermore, endothelial involvement could lead to platelet activation, thus altering coagulation and causing DIC, as described by the authors of the article. This fact per se could increase thrombin and prothrombin and trigger complement activation through C5.4 For instance, thrombotic microangiopathy has been reported in a patient with severe COVID-19, indicating a pathogenic relationship between these conditions.5 The potential role of ADAMTS13 deficiency in serious forms of the disease is another possible factor, as described by Huisman et al.6 in a recent article.
Additionally, the inflammatory route itself could activate complement through certain neutrophil serine proteases and macrophages.7 Consequently, we believe that there is a strong relationship between inflammation, complement, thrombotic microangiopathy, and coagulation in the pathogenesis of COVID-19. This may represent a new COVID-19–related inflammatory-microthrombotic syndrome which could explain the authors’ interesting findings.2–4
