Journal Article Ppublish
PubMed: 39749487 DOI: 10.1093/infdis/jiae645
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.
J Infect Dis 231(4):e723-e733
Authors: Victoria Dolange, Stefan Slamanig, Adam Abdeljawad, Tsoi Ying Lai, Nicholas Lemus, Gagandeep Singh, Juan Manuel Carreño, Anass Abbad, Komal Srivastava, Viviana Simon, Jaiprasath Sachithanandham, Andrew Pekosz, David Sullivan, Florian Krammer, Weina Sun, Peter Palese, Irene González-Domínguez
Affiliations
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York.
- Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands.
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York. Center for Vaccine Research and Pandemic Preparedness.
- Center for Vaccine Research and Pandemic Preparedness.
- Department of Pathology, Molecular and Cell-Based Medicine.
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
- Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Austria.
Abstract
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.
MeSH
Sars-Cov-2, Antibodies, Enzyme-Linked Immunosorbent Assay, Immunocompromised Host, Therapeutics, Severe Acute Respiratory Syndrome-Related Coronavirus, Communicable Diseases, Plasma, Immune Evasion