Determination of the concentration of IgG against the spike receptor-binding domain that predicts the viral neutralizing activity of convalescent plasma and serum against SARS-CoV-2
4 figures, 1 table. ; Passive immunization with hyperimmune plasma from convalescent patients has been proposed as a potentially useful treatment for COVID-19. Nevertheless, its efficacy in patients with COVID-19 remains uncertain. Thus, the establishment and validation of standardized methods that predict the viral neutralizing (VN) activity of plasma against SARS-CoV-2 is of utmost importance to appraise its therapeutic value. Using an in-house quantitative ELISA test and two independent cohorts with a total of 345 donors, we found that plasma and serum from most convalescent donors contained IgG antibodies specific to the spike receptor-binding domain (RBD) of SARS-CoV-2, with varying concentrations which correlate with previous disease severity and gender. Anti-RBD IgG plasma concentration significantly correlated with the plasma/serum VN activity against SARS-CoV-2 in vitro. ; Several hundred millions of people have been diagnosed of coronavirus disease 2019 (COVID-19), causing millions of deaths and a high socioeconomic burden. SARS-CoV-2, the causative agent of COVID-19, induces both specific T- and B-cell responses, being antibodies against the virus detected a few days after infection. Passive immunization with hyperimmune plasma from convalescent patients has been proposed as a potentially useful treatment for COVID-19. Using an in-house quantitative ELISA test, we found that plasma from 177 convalescent donors contained IgG antibodies specific to the spike receptor-binding domain (RBD) of SARS-CoV-2, although at very different concentrations which correlated with previous disease severity and gender. Anti-RBD IgG plasma concentrations significantly correlated with the plasma viral neutralizing activity (VN) against SARS-CoV-2 in vitro. Similar results were found using an independent cohort of serum from 168 convalescent health workers. These results validate an in-house RBD IgG ELISA test in a large cohort of COVID-19 convalescent patients and indicate that plasma from all convalescent donors does not contain a high enough amount of anti-SARS-CoV-2-RBD neutralizing IgG to prevent SARS-CoV-2 infection in vitro. The use of quantitative anti-RBD IgG detection systems might help to predict the efficacy of the passive immunization using plasma from patients recovered from SARS-CoV-2. ; This research was funded by grants from the Aragon Government (Fondo COVID-19), the Fundacion Santander-Universidad de Zaragoza (Programa COVID-19), and the Instituto de Salud Carlos III (COV20-00308). Work in the JP laboratory is funded by the FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón (Group B29_17R), Ministerio de Ciencia, Innovación y Universidades (MCNU), Agencia Estatal de Investigación (SAF2017-83120-C2-1-R), Fundacion Inocente Inocente, ASPANOA, and Carrera de la Mujer de Monzón. Work in the RH-G lab is funded by ARAID, MCNU (CTQ2013-44367-C2-2-P, BFU2016-75633-P, and PID2019-105451GB-I00), and Gobierno de Aragón (E34_R17 and LMP58_18) with FEDER (2014–2020) funds for "Building Europe from Aragón. LS was supported by a PhD fellowship (FPI) from the Ministry of Science, Innovation and Universities. IUM, SH and SR were supported by a PhD fellowship from Aragon Government. MA was supported by a post-doctoral fellowship "Juan de la Cierva-formación" from the Ministry of Science, Innovation and Universities and DdM by a post-doctoral fellowship "Sara Borrell". JP was supported by the ARAID Foundation. ; Peer reviewed