W171 - Immune Response to SARS-CoV-2, a Case of Original Antigenic Sin and Interference by IFNa-Alpha Autoantibodies? A Second-Third Wave COVID-19 Study of Unvaccinated Patients in Barcelona

Daniel Alvarez-Sierra – Immunology – IDIVAL, Santander, Spain; Monica Martinez-Gallo – Immunology – Hospital Universitari Vell d’Hebron; Marco Antonio Fernández-Sanmatin – Flowcytometry – Germans Trias i Pujol Research Institute; Roger Colobran – Immunologia – Vall Hebron Institute de Recerca (VHIR); Adrian Sanchez-Montalva – Infectious Diseases – Hospital Universitari Vell d’Hebron; Marina Garcia – Pediatria / Immunologia – all Hebron Institute de Recerca (VHIR); Alba Parra-Martinez – Pediatria / Immunologia – Vall Hebron Institute de Recerca (VHIR); Juan Espinosa-Pereiro – Infectious Diseases – Hospital Universitari Vell d’Hebron; Elisabet Poyatos-Canton – Immunology / Clinical laboratories – Hospital Materno Infantil Sant Joan de Deu, Barcelona; Coral Zurera-Egea – Immunology – Hospital Universitari Bellvitge; Alex Sánchez-Pla – Statistics and Bioinformatics – Universitat de Barcelona (UB); Eva Maria Martinez-Caceres – Immunology – Hospital Universitari Germans Trias I Pujol; Manuel Hernandez-Gonzalez – Immunology – Hospital Universitari Vell d’Hebron; Jordi Bas-Minguet – Immunology – Hospital Universitari Bellvitge; Aina Teniente Serra – Immunology – Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain

Abstract Text: After four years, the features of SARS-CoV-2 infection are well known but the extent of tissue damage that is due to the immune response rather than to direct viral action is not clear at the patient level.

In a cohort of 235 unvaccinated individuals including controls and asymptomatic, 128 were followed for and average of 25 days from symptoms onset. In these patients loess regression analysis of the isotype Ig responses to M, and N structural proteins revealed that only in five the response followed a primary pattern (IgM preceding IgG and IgA). By contrast, the response to RBD followed in most cases a primary pattern. There was a clear correlation between antibody titer, including anti-RBD and disease severity AS assessed by the WHO eight point score. Spectral flowcytometry of fresh PBMNCs showed that isotype switched B cells and Tfh lymphocytes appeared in circulation earlier and at higher level in mild than in moderate/severe cases, this including the CD4+CXCR5+CXCR3+ subset while in severe patients were the plasmablasts and plasma cells which appeared earlier.

IFN-alpha levels showed a consistent negative correlation with the antibody responses; interestingly, in 16 patients positive for IFN-alpha antibodies the antibody responses were stronger than in anti-IFN-alpha negative patients.
Overall theses finding will support the proposed view that the response to SARS-CoV-2 structural proteins are modulated in part by prior infections to circulating coronavirus (original antigenic sin). Immune response to SARS-CoV-2 is influenced by the effect of anti-IFN-alpha antibodies this hindering the interpretation of the responses.