In severe COVID-19, SARS-CoV-2 induces a chronic, TGF-β-dominated adaptive immune response
Ferreira-Gomes, M.; Kruglov, A.; Durek, P.; Heinrich, F.; Tizian, C.; Heinz, G. A.; Pascual-Reguant, A.; Du, W.; Mothes, R.; Fan, C.; Frischbutter, S.; Habenicht, K.; Budzinski, L.; Ninnemann, J.; Jani, P. K.; Guerra, G.; Lehmann, K.; Matz, M.; Ostendorf, L.; Heiberger, L.; Chang, H.-D.; Bauherr, S.; Maurer, M.; Schoenrich, G.; Raftery, M.; Kallinich, T.; Mall, M. A.; Angermair, S.; Treskatsch, S.; Doerner, T.; Corman, V. M.; Diefenbach, A.; Volk, H.-D.; Elezkurtaj, S.; Winkler, T. H.; Dong, J.; Hauser, A. E.; Radbruch, H.; Witkowski, M.; Melchers, F.; Radbruch, A.; Mashreghi, M.-F.
Show abstract
Here 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-{beta}-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-{beta}. 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-{beta}.
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