A surrogate ELISA to select high titer human convalescent plasma for treating immunocompromised patients infected with SARS-CoV-2 variants of concern.

Background: The emergence of new SARS-CoV-2 variants poses a new challenge for the treatment of immunocompromised patients against COVID-19. In this context, high titer COVID-19 Convalescent Plasma (CCP) is one of the few available therapeutics for these patients. We have revisited the selection of CCP samples and its efficacy against Omicron XBB.1.5 variant, dominant strain in 2023.

Methods: We have reviewed a surrogate enzyme-linked immunoassay (ELISA) to select CCP samples that will guarantee a protective level of neutralizing antibodies as the main correlate of protection. We analyzed antibody titers in 500 serum samples from a population-based serosurvey at Mount Sinai Hospital collected in early 2023 and validated the results with a set of CCP samples (collected 2020-2023) and confirmed its protection in an immunosuppressed mouse model.

Results: By using logistic regression modeling, we have redefined the definition of high titer CCP against the new variant in the post-pandemic era, where over 97% of the population have natural or vaccine-induced antibodies against the first SARS-CoV-2 strains. We next developed a new immunocompromised mouse model to validate the CCP in vivo against emerging variants. Equivalent to the two CCP units recommended for human use, the treatment of immunocompromised mice with two doses (100µL/dose) of CCP plasma via intraperitoneal injection showed a 46-fold reduction in lung viral titers 3-days-post-XBB.1.5-infection.

Conclusions: We believe the present results will guide future efforts in the selection of high titer CCP against emerging SARS-CoV-2 variants.