Prevalence and complement activation of anti-lymphocyte IgM antibodies in hospitalized COVID-19 patients

Abstract

Abstract Recent studies have shown that a proportion of COVID-19 patients develop auto-antibodies against a wide range of secreted and membrane proteins, some of which are expressed by lymphocytes. It is unclear, however, if and what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and whether they might have cytotoxic function. We systematically characterized the presence, isotype and lytic function of ALAb in a cohort of 85 COVID-19 patients during hospital admission from May 2020 to June 2022. As controls we analyzed 20 healthy donors (HD) and seven Flu infected volunteers. Patients were assigned into mild (N=65), or moderate/severe (N=20) groups, based on oxygen requirements, and 37 patients were followed up after recovery. We found that 27% of COVID-19 patients had IgM ALAb (binding CD4, CD8 and/or B cells), compared to 15% of the control populations. IgM ALAb prevalence was independent of disease severity and persisted during early convalescence. Sera from some of the IgM ALAb positive COVID-19 patients, and not from the controls, induced complement dependent cytotoxicity (CDC) of HD PBMCs, mostly targeting B cells. Complement activation was corroborated by detecting complement deposition ex vivo on lymphocytes from 70% of COVID-19 acutely infected patients. The level of C3b deposition on CD4 T cells inversely correlated with CD4 numbers in blood of moderate/severe patients. Our findings indicate that the antibody mediated auto-immune response found in COVID-19 patients includes targeting of lymphocytes with potential contribution to the observed lymphopenia. This work was supported by the Divisions of Intramural Research of NIAID and NIBIB of the NIH