Campos Mata, Leire de, 1991-Tejedor Vaquero, Sonia, 1988-Tachó-Piñot, RoserPiñero González, Janet, 1977-Grasset, Emilie K.Arrieta Aldea, ItziarRodrigo Melero, NataliaCarolis, CarloHorcajada Gallego, Juan PabloCerutti, Andrea, 1965-Villar García, JuditMagri, Giuliana, 1978-2022-01-122022-01-122021Campos-Mata LD, Tejedor Vaquero S, Tachó-Piñot R, Piñero J, Grasset EK, Arrieta Aldea I et al. SARS-CoV-2 sculpts the immune system to induce sustained virus-specific naïve-like and memory B-cell responses. Clin Transl Immunology. 2021 Sep 5;10(9):e1339. DOI: 10.1002/cti2.13392050-0068http://hdl.handle.net/10230/52188Objectives: SARS-CoV-2 infection induces virus-reactive memory B cells expressing unmutated antibodies, which hints at their emergence from naïve B cells. Yet, the dynamics of virus-specific naïve B cells and their impact on immunity and immunopathology remain unclear. Methods: We longitudinally profiled SARS-CoV-2-specific B-cell responses in 25 moderate-to-severe COVID-19 patients by high-dimensional flow cytometry and isotyping and subtyping ELISA. We also explored the relationship of B-cell responses to SARS-CoV-2 with the activation of effector and regulatory cells from the innate or adaptive immune system. Results: We found a virus-specific antibody response with a broad spectrum of classes and subclasses during acute infection, which evolved into an IgG1-dominated response during convalescence. Acute infection was associated with increased mature B-cell progenitors in the circulation and the unexpected expansion of virus-targeting naïve-like B cells. The latter further augmented during convalescence together with virus-specific memory B cells. In addition to a transitory increase in tissue-homing CXCR3+ plasmablasts and extrafollicular memory B cells, most COVID-19 patients showed persistent activation of CD4+ and CD8+ T cells along with transient or long-lasting changes of key innate immune cells. Remarkably, virus-specific antibodies and the frequency of naïve B cells were among the major variables defining distinct immune signatures associated with disease severity and inflammation. Conclusion: Aside from providing new insights into the complexity of the immune response to SARS-CoV-2, our findings indicate that the de novo recruitment of mature B-cell precursors into the periphery may be central to the induction of antiviral immunity.application/pdfeng© 2021 Leire de Campos-Mata et al. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposesCOVID-19 (Malaltia)GenèticaSistema immunològicinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/cti2.1339info:eu-repo/semantics/openAccess