Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients

• DOI: 10.1016/j.imbio.2021.152093
• Publication Date: 2021-05-09T22:48:52Z
• Authors: Aymric Kisserli; Nathalie Schneider; Sandra Audonnet; Thierry Tabary; Antoine Goury; Joel Cousson; Rachid Mahmoudi; Firouze Bani-Sadr; Lukshe Kanagaratnam; Damien Jolly; Jacques HM Cohen
• Keywords: 0301 basic medicine; Erythrocytes; SARS-CoV-2; [SDV]Life Sciences [q-bio]; 610; COVID-19; Antigen-Antibody Complex; Article; Peptide Fragments; 3. Good health; [SDV] Life Sciences [q-bio]; Intensive Care Units; 03 medical and health sciences; Gene Expression Regulation; 616; Complement C4b; Receptors, Complement 3b; Humans; France; Complement Activation

ABSTRACTWe determined CR1, CD35 the C3b, C4b receptor density, C3b/C3bi and C4d deposits densities on Erythrocytes (E) in 51 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims France. A clear acquired decrease of CR1 density of E from COVID-19 patients was observed, particularly among fatal cases, and paralleling several severity parameters.Deposits of C4d largely above values observed in normal individuals, mostly without C3 deposits, have been observed in more than 80% of the patients, reminiscent of the sub endothelial pericapillary deposits in organ transplant rejection, already observed on E in parallel, as well as also observed on E in clinical SLE flares.Conversely, significant C3 deposits were only observed among ¼ of the patients. The decrease of CR1/E density, and the detection of virus spike, C3 or C4 fragment on E, among COVID-19 patients, are likely to be two aspects of the same phenomenon of immune complexes or complement fragment coated cell debris handling and clearance.Measurement of C4d deposit on E might represent a way for assessing inflammation and complement activation occurring in organ capillaries. CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients.Taken together, these original findings stress on the participation of the complement regulatory proteins in that disease and evidence that E matter in immune mechanisms in COVID-19 patients.The use of CR1, or CR1-like molecules with the aim of down regulating complement activation and inflammation for therapy should also be considered.HIGHLIGHTSAcquired decrease of CR1 on E in COVID-19 patients, particularly among fatal cases, and paralleling several severity parameters.Large C4d deposits on E in most patients, reminiscent of the pericapillary deposits in organ transplant rejection, already observed on E in parallel, as well as on E from SLE flares.C4d deposit on E, a possible way for assessing inflammation and complement activation in organ capillaries.Decreased CR1/E, a possible cumulative index of complement activation in COVID-19 patients.The use of CR1 or CR1-like molecules for down regulating complement activation for therapy should also be considered.