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This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (grants SLD016 to J.B. and SLD015 to J.C.), the Spanish Health Institute Carlos III and the European Regional Development Fund (grant PI17/01518 and PI20/00093 to J.B. and PI18/01332 to J.C.), CERCA Programme/Generalitat de Catalunya 2017 SGR 252, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat, and Correos. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. E.P. was supported by a doctoral grant from the National Agency for Research and Development of Chile (ANID) (72180406). We are grateful to all participants and the technical staff of IrsiCaixa for sample processing. Francesc Lo ' pez-Segui ' provided medical writing support during the preparation of the manuscript.

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Clinical course impacts early kinetics, magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection

Publicat a:Cell Reports Medicine . 3 (2): 100523- - 2022-02-15 3(2), DOI: 10.1016/j.xcrm.2022.100523

Autors: Pradenas, Edwards; Trinite, Benjamin; Urrea, Victor; Marfil, Silvia; Tarres-Freixas, Ferran; Ortiz, Raquel; Rovirosa, Carla; Rodon, Jordi; Vergara-Alert, Julia; Segales, Joaquim; Guallar, Victor; Valencia, Alfonso; Izquierdo-Useros, Nuria; Noguera-Julian, Marc; Carrillo, Jorge; Paredes, Roger; Mateu, Lourdes; Chamorro, Anna; Toledo, Ruth; Massanella, Marta; Clotet, Bonaventura; Blanco, Julia

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To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Longterm neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short-and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses.

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