Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 patients.

Abstract

SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the outcome of COVID-19. We investigated whether the specific immune responses in the peripheral blood of 276 patients were associated with the severity and progression of COVID-19. At admission, dramatic lymphopenia of T, B, and NK cells is associated with severity. Conversely, the proportion of B cells, plasmablasts, circulating follicular helper T cells (cTfh) and CD56- CD16+ NK-cells increased. Regarding humoral immunity, levels of IgM, IgA, and IgG were unaffected, but when degrees of severity were considered, IgG was lower in severe patients. Compared to healthy donors, complement C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, while the activation peptide of C5 (C5a) increased from the admission in every patient, regardless of their severity. Moreover, total IgG, the IgG1 and IgG3 isotypes, and C4 decreased from day 0 to day 10 in patients who were hospitalized for more than two weeks, but not in patients who were discharged earlier. Our study provides important clues to understand the immune response observed in COVID-19 patients, associating severity with an imbalanced humoral response, and identifying new targets for therapeutic intervention.

• Authors: Ana Marcos-Jiménez, Santiago Sánchez-Alonso, Ana Alcaraz-Serna, Laura Esparcia, Celia López-Sanz, Miguel Sampedro-Núñez, Tamara Mateu-Albero, Ildefonso Sánchez-Cerrillo, Pedro Martínez-Fleta, Ligia Gabrie, Luciana Del Campo Guerola, José Miguel Rodríguez-Frade, José M Casasnovas, Hugh T Reyburn, Mar Valés-Gómez, Margarita López-Trascasa, Enrique Martín-Gayo, María José Calzada, Santos Castañeda, Hortensia de la Fuente, Isidoro González-Álvaro, Francisco Sánchez-Madrid, Cecilia Muñoz-Calleja, Arantzazu Alfranca
• Journal: European journal of immunology (Eur J Immunol) Vol. 51 Issue 3 Pg. 634-647 (03 2021) ISSN: 1521-4141 [Electronic] Germany
• PMID: 33251605 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Chemical References

• C3 protein, human
• Complement C3
• Complement C4
• Complement C5
• Immunoglobulin A
• Immunoglobulin G
• Immunoglobulin M
• Immunoglobulins

Topics

• Aged
• B-Lymphocytes (immunology)
• COVID-19 (immunology, pathology)
• Complement C3 (analysis)
• Complement C4 (analysis)
• Complement C5 (analysis)
• Female
• Humans
• Immunoglobulin A (blood)
• Immunoglobulin G (blood)
• Immunoglobulin M (blood)
• Immunoglobulins (blood)
• Killer Cells, Natural (immunology)
• Lymphocyte Count
• Lymphopenia (immunology)
• Male
• Middle Aged
• Respiratory Distress Syndrome (immunology, pathology)
• SARS-CoV-2 (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)