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.
- 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. M.
- Lehmann, K.
- Matz, M.
- Ostendorf, L.
- Heiberger, L.
- Chang, H. D.
- Bauherr, S.
- Maurer, M.
- Schönrich, G.
- Raftery, M.
- Kallinich, T.
- Mall, M. A.
- Angermair, S.
- Treskatsch, S.
- Dörner, 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.
