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

Victoria Dolange; Stefan Slamanig; Adam Abdeljawad; Tsoi Lai Ying; Nicholas Lemus; Gagandeep Singh; Juan Manuel Carreño; Anass Abad; Komal Srivastava; Viviana Simon; Jaiprasath Sachithanandham; Andrew Pekosz; David Sullivan; Florian Krammer; Weina Sun; Peter Palese; Irene González-Domínguez

doi:10.1093/infdis/jiae645

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

J Infect Dis. 2025 Jan 3:jiae645. doi: 10.1093/infdis/jiae645. Online ahead of print.

Authors

Victoria Dolange¹, Stefan Slamanig^{1

2}, Adam Abdeljawad¹, Tsoi Lai Ying¹, Nicholas Lemus¹, Gagandeep Singh^{1

3}, Juan Manuel Carreño^{1

3}, Anass Abad^{1

3}, Komal Srivastava^{1

3}, Viviana Simon^{1

3

4

5}, Jaiprasath Sachithanandham⁶, Andrew Pekosz⁶, David Sullivan⁶, Florian Krammer^{1

3

4

7}, Weina Sun¹, Peter Palese^{1

5}, Irene González-Domínguez¹

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
² Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
³ Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁷ Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria.

PMID: 39749487
DOI: 10.1093/infdis/jiae645

Abstract

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.

Keywords: SARS-Cov-2; correlates of protection; immune evasion; variants of concern.

© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.