Abstract
The novel coronavirus disease (COVID-19) has become a universally prevalent infectious disease. The causative virus of COVID-19 is severe acute respiratory syndrome coronavirus type 2. Recent retrospective clinical studies have established a significant association between the incidence of vascular thrombotic events and the severity of COVID-19. The enhancement in serum levels of markers that reflect a hypercoagulable state has been suggested to indicate a poor prognosis. Therefore, at present, it is crucial to understand the mechanisms that foster the hypercoagulable state in COVID-19. Over-activated inflammatory response, which is manifested as excessive cytokine release in COVID-19 patients, is also associated with COVID-19 severity. This review discusses the immuno-pathological basis of the excessive cytokine release in COVID-19. Besides, this article reviews the role of pro-inflammatory or anti-inflammatory cytokines, whose significant elevations in their serum levels have been consistently detected in multiple different clinical studies, in promoting the hypercoagulable state. Since the expression of angiotensin-converting enzyme 2 (ACE2) is potentially down-regulated in COVID-19, as proposed by a recent bio-informatic analysis, mechanisms through which reduced ACE2 expressions promote vascular thrombosis are summarized. In addition, the reciprocal-enhancing effects of the excessive cytokine release and the downregulated ACE2 expression on their pro-thrombotic activities are further discussed. Here, based on currently available evidence, we review the pathogenic mechanisms of the hypercoagulable state associated with severe cases of COVID-19 to give insights into prevention and treatment of the vascular thrombotic events in COVID-19.
Keywords: ACE2; COVID-19; Excessive cytokine release; Hypercoagulable state; Vascular thrombotic events.
【저자키워드】 COVID-19, ACE2, Hypercoagulable state, Excessive cytokine release, Vascular thrombotic events., 【초록키워드】 Treatment, coronavirus disease, coronavirus, Cytokines, thrombosis, severity, COVID-19 severity, cytokine, Infectious disease, novel coronavirus disease, virus, angiotensin-converting enzyme 2, Novel coronavirus, activity, severity of COVID-19, severe cases, Clinical studies, incidence, respiratory, ACE2 expression, expression, pathogenic mechanism, Thrombotic events, mechanism, COVID-19 patients, Hypercoagulable state, association, Angiotensin-converting enzyme, marker, clinical study, Evidence, retrospective, Inflammatory response, Analysis, angiotensin, hypercoagulable, foster, acute respiratory syndrome, Vascular, Serum level, serum levels, poor prognosis, Elevation, thrombotic, Severe case, present, cytokine release, enhancement, pathogenic mechanisms, vascular thrombosis, pro-inflammatory, anti-inflammatory cytokines, Effect, recent, thrombotic event, prevalent, addition, reduced, suggested, promote, manifested, downregulated, down-regulated, pro-thrombotic, with COVID-19, 【제목키워드】 cytokine, Hypercoagulable state, down-regulation, cytokine release,