In severe COVID-19, SARS-CoV-2 induces a chronic, TGF-β-dominated adaptive immune response
Author:
Ferreira-Gomes Marta, Kruglov Andrey, Durek Pawel, Heinrich Frederik, Tizian Caroline, Anne Heinz Gitta, Pascual-Reguant Anna, Du Weijie, Mothes Ronja, Fan Chaofan, Frischbutter Stefan, Habenicht Katharina, Budzinski Lisa, Ninnemann Justus, Jani Peter K., Guerra Gabriela, Lehmann Katrin, Matz Mareen, Ostendorf Lennard, Heiberger Lukas, Chang Hyun-Dong, Bauherr Sandy, Maurer Marcus, Schönrich Günther, Raftery Martin, Kallinich Tilmann, Alexander Mall Marcus, Angermair Stefan, Treskatsch Sascha, Dörner Thomas, Max Corman Victor, Diefenbach Andreas, Volk Hans-Dieter, Elezkurtaj Sefer, Winkler Thomas H., Dong Jun, Erika Hauser Anja, Radbruch Helena, Witkowski Mario, Melchers Fritz, Radbruch Andreas, Mashreghi Mir-FarzinORCID
Abstract
AbstractHere we have analyzed the dynamics of the adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected by activated B cells egressing into the blood, at the single cell level. Early on, before seroconversion in response to SARS-CoV-2 spike protein, activated peripheral B cells displayed a type 1 interferon-induced gene expression signature. After seroconversion, activated B cells lost this signature, expressed IL-21- and TGF-β-induced gene expression signatures, and mostly IgG1 and IgA1. In the sustained immune reaction of the COVID-19 patients, until day 59, activated peripheral B cells shifted to expression of IgA2, reflecting instruction by TGF-β. Despite the continued generation of activated B cells, those cells were not found in the lungs of deceased COVID-19 patients, nor did the IgA2 bind to dominant antigens of SARS-CoV-2. In severe COVID-19, SARS-CoV-2 thus triggers a chronic immune reaction distracted from itself and instructed by TGF-β.
Publisher
Cold Spring Harbor Laboratory
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