Abstract
Numerous publications have underlined the link between complement C5a and the clinical course of COVID-19. We previously reported that levels of C5a remain high in the group of severely ill patients up to 90 days after hospital discharge. We have now evaluated which complement pathway fuels the elevated levels of C5a during hospitalization and follow-up. The alternative pathway (AP) activation marker C3bBbP and the soluble fraction of C4d, a footprint of the classical/lectin (CP/LP) pathway, were assessed by immunoenzymatic assay in a total of 188 serial samples from 49 patients infected with SARS-CoV-2. Unlike C5a, neither C3bBbP nor C4d readouts rose proportionally to the severity of the disease. Detailed correlation analyses in hospitalization and follow-up samples collected from patients of different disease severity showed significant positive correlations of AP and CP/LP markers with C5a in certain groups, except for the follow-up samples of the patients who suffered from highly severe COVID-19 and presented the highest C5a readouts. In conclusion, there is not a clear link between persistently high levels of C5a after hospital discharge and markers of upstream complement activation, suggesting the existence of a non-canonical source of C5a in patients with a severe course of COVID-19.
Keywords: C5a; COVID-19; anaphylatoxin; clinical risk score; complement system.
【저자키워드】 COVID-19, C5a, anaphylatoxin, complement system., clinical risk score, 【초록키워드】 severe COVID-19, Hospitalization, severity, disease severity, complement, Clinical course, Patient, pathway, Follow-up, correlation, Alternative pathway, marker, C4d, Complement pathway, Activation, positive correlation, hospital discharge, clinical risk, upstream, Course, highest, collected, reported, the patient, the disease, evaluated, elevated, analysis, suffered, groups, Numerous, infected with SARS-CoV-2, severely ill patient, soluble fraction, were assessed, 【제목키워드】 severe COVID-19, complement, convalescent, marker, C4d, Activation,