| Literature DB >> 33785765 |
Marta Ferreira-Gomes1, Andrey Kruglov1,2,3, Pawel Durek1, Frederik Heinrich1, Caroline Tizian4,5,6, Gitta Anne Heinz1, Anna Pascual-Reguant1,7, Weijie Du1, Ronja Mothes1,8, Chaofan Fan1, Stefan Frischbutter9, Katharina Habenicht10, Lisa Budzinski1, Justus Ninnemann1, Peter K Jani1, Gabriela Maria Guerra1, Katrin Lehmann1, Mareen Matz11, Lennard Ostendorf1,8, Lukas Heiberger1, Hyun-Dong Chang1,12, Sandy Bauherr1, Marcus Maurer9, Günther Schönrich13, Martin Raftery13, Tilmann Kallinich1,5,14, Marcus Alexander Mall5,14,15, Stefan Angermair16, Sascha Treskatsch16, Thomas Dörner1,7, Victor Max Corman13, Andreas Diefenbach4,5,6, Hans-Dieter Volk11,17, Sefer Elezkurtaj18, Thomas H Winkler10, Jun Dong1, Anja Erika Hauser1,7, Helena Radbruch8, Mario Witkowski4,5,6, Fritz Melchers1, Andreas Radbruch1, Mir-Farzin Mashreghi19,20.
Abstract
The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.Entities:
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Year: 2021 PMID： 33785765 DOI： 10.1038/s41467-021-22210-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919