ABSTRACT
IntroductionA cohort of COVID-19 convalescent volunteers allowed the study of neutralizing (nAb) and ligand antibodies kinetics by providing sequential samples during a median of 100 days after onset of disease. Material and MethodsA cohort of previously RT-PCR+ve (detected by nasopharyngeal swab during the acute phase), male convalescent patients, all with mild symptoms, were enrolled on serial blood sample collection for evaluation of longitudinal nAb titers and anti-nucleocapsid (NP) antibodies (IgM, IgG and IgA). Nabs were detected by a cytopathic effect-based virus neutralization test (CPE-based VNT), carried out with SARS-CoV-2 (GenBank: MT350282) ResultsA total of 78 male volunteers provided 316 samples, spanning a total of 4820 days of study. Although only 25% of donors kept nAb titers [≥]160, after a median of 100 days after the onset of disease, there was a high probability of sustaining nAB titers [≥]160 in volunteers whose initial nAb titer was [≥]1280, weight [≥] 90kg or BMI classified as overweight or obese, evidenced by Kaplan-Meier estimates and Cox hazard regression. There was no correlation between ABO group, ABO antibody titers and persistent high nAb titers. High IgG anti-NP (S/CO [≥]5.0) is a good surrogate for detecting nAB [≥]160, defined by ROC curve (sensitivity = 90.5%; CI95% 84.5-94.7%) ConclusionSelection of CCP donors for multiple collections based on initial high nAb titers ([≥]1280) or overweight/obese (BMI) provides a simple strategy to achieve higher quality in CCP programs. High IgG anti-NP levels can also be used as surrogate markers for high nAb screening.
ABSTRACT
BackgroundPassive antibody therapy with convalescent plasma (CP) represents a promising alternative for the treatment of SARS-CoV-2 infection. The efficacy of CP therapy has been associated with high titers of neutralizing antibodies (nAbs) in the plasma of recovered patients, but the assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti-SARS-CoV-2 immunoassays and the clinical characteristics of the CP potential donors. MethodsTwo hundred and fourteen CP donors were enrolled and tested for the presence of anti-SARS-CoV-2 antibodies using two commercial immunoassays (IA): Anti-SARS-CoV-2 ELISA IgG EUROIMMUN and Anti-SARS-CoV-2 Chemiluminescence IgG Abbott. In parallel, quantification of neutralizing antibodies (nAbs) was performed using the Cytopathic effect-based virus neutralization test (CPE-VNT). Three criteria for identifying donors with high titers of nAbs ([≥]1:160) were tested: - Criterion1: Curve ROC Method; - Criterion 2: Conditional decision tree considering only the results from the IA and -Criterion 3: Conditional decision tree including both the IA results and the clinical variables. ResultsThe performance of Abbott and EUROIMMUN immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers [≥] 1:160. Regarding the three studied criteria for identifying CP donors with high nAbs titers ([≥] 1:160): 1) Criterion 1 showed 76.1% accuracy when the S/CO cut-off of 4.65 was used, 2) Criterion 2 presented 76.1% accuracy if the S/CO [≥] 4.57 was applied and 3) Criterion 3 had 71.6% accuracy if either S/CO [≥] 4.57 or S/CO between 2.68 and 4.57 and the last COVID-19-related symptoms occurred less than 19 days from donor recruiting were used. ConclusionThe results of SARS-CoV-2 immunoassays (S/CO) can be used to predict high nAbs titers of potential CP donors. This study has proposed three different criteria for identifying donors with [≥] 1:160 nAbs titer based on either solely S/CO results or S/CO together with clinical variables, all with high efficacy and accuracy.
