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

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About: Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19 Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19
Creator	Alcaraz-Serna, Ana Alfranca, Arantzazu Calzada, María Castañeda, Santos De La Fuente, Hortensia Del Campo Guerola, Luciana Esparcia, Laura Gabrie, Ligia González-Álvaro, Isidoro López-Sanz, Celia López-Trascasa, Margarita Marcos-Jiménez, Ana Martín-Gayo, Enrique Martínez-Fleta, Pedro Mateu-Albero, Tamara Muñoz-Calleja, Cecilia Sampedro-Núñez, Miguel Sánchez-Madrid, Francisco Sánchez-Alonso, Santiago Sánchez-Cerrillo, Ildefonso
source	MedRxiv
abstract	Background: SARS-CoV-2 infection causes an abrupt response by the host immune system, which is largely responsible for the pathogenesis and outcome of COVID-19. We aimed to investigate which specific responses from either cellular or humoral immunity associate to severity and progression of COVID-19. Methods: A cohort of 276 patients classified in mild, moderate and severe, was studied. Peripheral blood lymphocyte subpopulations were quantified by flow cytometry, and immunoglobulins and complement proteins by nephelometry. Results: At admission, dramatic lymphopenia of T, B and NK cells associated to severity. However, only the proportion of B cells increased, while T and NK cells appeared unaffected. Accordingly, the number of plasma cells and circulating follicular helper T cells (cTfh) increased, but levels of IgM, IgA and IgG were unaffected. When degrees of severity were considered, IgG was lower in severe patients, suggesting an IgG consumption by complement activation or antibody-dependent cellular cytotoxicity (ADCC). Activated CD56-CD16+ NK-cells, which mediate ADCC, were increased. Regarding complement, C3 and C4 protein levels were higher in mild and moderate, but not in severe patients, compared to healthy donors. Moreover, IgG 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. Conclusion: Our study provides important clues to understand the immune response observed in COVID-19 patients, which is probably related to viral clearance, but also underlies its pathogenesis and severity. This study associates for the first time COVID-19 severity with an imbalanced humoral immune response characterized by excessive consumption of IgG and C4, identifying new targets for therapeutic intervention.
has issue date	2020-06-17(xsd:dateTime)
bibo:doi	10.1101/2020.06.15.20131706
has license	medrxiv
sha1sum (hex)	355d66816ce878f32ab0da34827c10311bb37bd1
schema:url	https://doi.org/10.1101/2020.06.15.20131706
resource representing a document's title	Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID-19
resource representing a document's body	covid:355d66816ce878f32ab0da34827c10311bb37bd1#body_text
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