Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates

BACKGROUND. SARS-CoV-2-specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2-neutralizing antibodies (nAbs) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood. METHODS. Potential convalescent plasma donors with virologically documented SARS-CoV-2 infection were tested for serum IgG against SARS-CoV-2 spike protein S1 domain and against nucleoprotein (NP), and for nAb. RESULTS. Among 250 consecutive persons, including 27 (11%) requiring hospitalization, who were studied a median of 67 days since symptom onset, 97% were seropositive on 1 or more assays. Sixty percent of donors had nAb titers >= 1:80. Correlates of higher nAb titers included older age (adjusted OR [AOR] 1.03 per year of age, 95% CI1.00-1.06), male sex (AOR 2.08, 95% CI1.13-3.82), fever during illness (AOR 2.73, 95% CI1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI1.32-32.95). Receiver operating characteristic analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. nAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range 77-120) apart (P < 0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses. CONCLUSION. nAb titers correlated with COVID-19 severity, age, and sex. SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels declined, and a small proportion of convalescent individuals lacked adaptive immune responses.

Automated summary

SARS-CoV-2-specific antibodies in convalescent plasma could potentially provide protection from reinfection and disease. nAb titers correlated with COVID-19 severity, age, and sex, serving as useful surrogates for plasma donor selection. Functional nAb levels declined over time, and a small proportion of convalescent individuals lacked adaptive immune responses.