Leire De Campos Mata, Janet Pinero, Sonia Tejedor Vaquero, Roser Tachó-Piñot, Maria Kuksin, Itziar Arrieta Aldea, Natalia Rodrigo Melero, Carlo Carolis, Laura Furlong, Andrea Cerutti, Judit Villar-Garcia, Giuliana Magri
Abstract
The production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
We want to particularly acknowledge the patients and the Parc de Salut Mar MARBiobanc (PT17/0015/0011) integrated in the Spanish National Biobanks Network from ISCIII for their collaboration. MARBiobanc work was supported by grants from Instituto de Salud Carlos III/FEDER (PT17/0015/0011) and the Xarxa de Bancs de tumors sponsored by Pla Director d Oncologia de Catalunya (XBTC). This study was supported by the COVID 19 call grant from Generalitat de Catalunya, Department of Health (to G.M and L.D.C.M) and grant Miguel Servet research program (to G.M). IMI/JU resources of which are composed of financial contribution from the EU/FP7 (FP7 2007/2013) and EFPIA companies in kind contribution (116030 to TransQST, 777365 to eTRANSAFE),and the EU H2020 Programme 2014/2020 (676559 to Elixir-Excelerate); Agencia de Gestio d Ajuts Universitaris i de Recerca Generalitat de Catalunya (2017SGR00519). The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and FEDER (PRB2/ISCIII (PT13/0001/0023, of the PE I+D+i 2013/2016). The DCEXS is a Unidad de Excelencia Maria de Maeztu, funded by the MINECO (MDM-2014-0370).
https://www.medrxiv.org/content/10.1101/2020.12.18.20248461v1
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