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Thrombotic Microvascular Injury is not Mediated by Thrombotic Micro Angiopathy Despite Systemic Complement Activation in COVID-19 Patients

Adrien De Voeght, Doriane Calmes, Floran Beck, Jean-Baptiste Sylvestre, Philippe Delvenne, Pierre Peters,Gaelle Vertenoeil, Frédéric Baron, Nathalie Layios, Jean-Luc Canivet

Hypoxemia and coagulopathy are common in severe symptomatic patients of coronavirus disease 2019 (COVID-19). Histological evidence shows implication of complement activation and lung injury. We prospectively research sign of complement activation and presence of thrombotic microangiopathy in 8 severe patients. Six of them presented moderate elevation of final pathway of complement –sC5b-9 (median value: 350 ng/mL [IQR: 300,5-514,95 ng/mL]). Two patients have been autopsied and presence of thrombotic microvascular injury has been found. Interestingly, none the 8 patients had signs of mechanical hemolytic anemia (median value of hemoglobin : 10,5 gr/dL[IQR : 8,1-11,9], median value of haptoglobuline 4,49 [IQR 3,55-4,66], none of the patients has schistocyte) and thrombocytopenia (median value: 348000/mL [IQR : 266 000-401 000). Finally, all 8 patients had elevated d-dimer (median value: 2226 μgr/l [IQR: 1493–2362]) and soluble fibrin monomer complex (median value: 8.5 mg/mL, IQR [<6–10.6]). In summary, this study show moderate activation of complement and coagulation with presence of thrombotic microvascular injury in patients with severe COVID-19 without evidence of systemic thrombotic microangiopathy.