Coagulopathy, endothelial dysfunction, thrombotic microangiopathy and complement activation: potential role of complement system inhibition in COVID-19

Abstract

Coronavirus disease-2019 (COVID-19) is a rapidly evolving health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a novel disease entity and we are in a learning phase with regards to the pathogenesis, disease manifestations, and therapeutics. In addition to the primary lung injury, many patients especially the ones with moderate to severe COVID-19 display evidence of endothelial damage, complement activation, which leads to a pro-coagulable state. While there are still missing links in our understanding, the interplay of endothelium, complement system activation, and immune response to the SARS-CoV-2 virus is a surprisingly major factor in COVID-19 pathogenesis. One could envision COVID-19 becoming a novel hematological syndrome. This review is to discuss the available literature with regards to the involvement of the complement system, and coagulation cascade and their interaction with endothelium.

Kidney Thrombotic Microangiopathy After COVID-19 Associated With C3 Gene Mutation

“…The arguments against this hypothesis are the presence of glomerular TMA (which are absent in IgA-associated TMA) and the presence of the pathogenic mutation of the alternative complement pathway. Moreover, in the present case, the IgA-nephropathy was stable until the patient developed the COVID-19 and this makes more likely that the virus acted as a trigger for complement activation ( 4 , 5 , 6 ). So, we should consider that IgA nephropathy and aHUS due to COVID-19 are two concomitant diseases.…”

“…The thrombotic events can occur despite the patients receiving thromboprophylaxis. There are also preliminary reports of lupus anticoagulant, anti-β2-glycoprotein I and anticardiolipin or other antiphospholipid antibodies implicated in COVID-19 coagulopathy ( 4 , 5 , 6 ). A case of TMA associated with COVID-19 reported by Jhaveri ( 9 ) was characterized with diffuse cortical necrosis and widespread microthrombi in the kidney biopsy.…”

“…Conventional treatment of aHUS includes TPE, hemodialysis and increasingly humanized monoclonal antibody C5-inhibitor ( 4 , 5 , 6 ). We were concerned about the benefits to risk ratio of TPE during a severe infection such as COVID-19.…”

“…We were concerned about the benefits to risk ratio of TPE during a severe infection such as COVID-19. Humoral immunity is of critical importance in clearing SARS-CoV-2, and treatment with convalescent plasma containing viral-specific neutralizing antibodies has even been used to treat critically ill COVID-19 patients ( 4 , 5 ). In this context, we were very cautious before using TPE as the procedure itself might remove critically important neutralizing antibodies against SARS-CoV-2.…”

Correlation of Coagulation Parameters With Clinical Outcomes During the Coronavirus-19 Surge in New York: Observational Cohort

“…This difference is likely a reflection of the higher hemodialysis needs in non-survivors compared to survivors (90% vs. 48%). Nonetheless, the observation of ex vivo clots in hemodialysis lines despite anticoagulation suggests that this disease may present with more of a thrombotic microangiopathy (TMA) picture and may be more amenable to TMA therapeutics ( Henry et al, 2020 ; Sweeney et al, 2020 ; Wang et al, 2020 ; Cugno et al, 2021 ). Studies are ongoing looking at therapies with anticoagulation, anti-complement, fibrinolysis ( Bikdeli et al, 2020 ; Laurence et al, 2020 ).…”