SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection. This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (Grant DSL0016 to JB and Grant DSL015 to JC), the Spanish Health Institute Carlos III (Grant PI17/01518 and PI18/01332 to JC) 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. EP was supported by a doctoral grant from National Agency for Research and Development (ANID)—Formation of Advanced Human Capital Program, Becas Chile: Grant 72180406. We are deeply grateful to all participant and to the technical staff of IrsiCaixa for sample processing. We also thank Daniel Pérez-Zsolt and Jordana Muñoz-Basagoiti for assistance with ACE-2 expressing 293T cell culture. Peer Reviewed "Article signat per 26 autors/es: Benjamin Trinité, Ferran Tarrés-Freixas, Jordi Rodon, Edwards Pradenas, Víctor Urrea, Silvia Marfil, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Carmen Aguilar-Gurrieri, Ana Barajas, Raquel Ortiz, Roger Paredes, Lourdes Mateu, Alfonso Valencia, Víctor Guallar, Lidia Ruiz, Eulàlia Grau, Marta Massanella, Jordi Puig, Anna Chamorro, Nuria Izquierdo-Useros, Joaquim Segalés, Bonaventura Clotet, Jorge Carrillo, Júlia Vergara-Alert & Julià Blanco"