A Surrogate Enzyme-Linked Immunosorbent Assay to Select High-Titer Human Convalescent Plasma for Treating Immunocompromised Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

BACKGROUND: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges the treatment of immunocompromised patients against coronavirus disease 2019 (COVID-19). High-titer COVID-19 convalescent plasma (CCP) remains one of the few available therapeutics for these patients. We have revisited the selection of CCP samples and evaluated their efficacy against the Omicron XBB.1.5 variant, the dominant strain in 2023. METHODS: A surrogate enzyme-linked immunoassay was reviewed to select CCP samples that ensure a protective level of neutralizing antibodies as the main correlate of protection. Antibody titers were analyzed in 500 serum samples from a population-based serosurvey at Mount Sinai Hospital in early 2023, and the results were validated with CCP samples (collected in 2020-2023) using an immunosuppressed mouse model. RESULTS: Using logistic regression modeling, we have redefined high-titer CCP against the new variant in the postpandemic era, where over 97% of the population has natural or vaccine-induced antibodies against earlier SARS-CoV-2 strains. Treatment of immunocompromised mice with two doses (100 μL/dose) of CCP plasma via intraperitoneal injection reduced lung viral titers by 46-fold 3 days post-XBB.1.5 infection. CONCLUSIONS: These findings will guide future efforts in selecting high-titer CCP for emerging SARS-CoV-2 variants.