Background/Case Studies: With SARS-CoV-2 variants challenging COVID-19 monoclonal antibody therapies, COVID-19 convalescent plasma (CCP) remains an important option for immunocompromised patients. Current US regulatory criteria for qualifying CCP as high titer requires plasma to be collected from symptomatic individuals within 6 months of diagnosis, and test above qualifying binding antibody levels on specific authorized anti-SARS-CoV-2 tests. In this study, the Vitros® Anti-SARS-CoV-2 IgG Quantitative test (Vitros IgGQ) was used to measure spike-binding antibody levels in serial samples in repeat blood donors who were infected and/or vaccinated, and their neutralization activity was characterized against SARS-CoV-2 variants of concern.
Study
Design/Methods: Longitudinal plasma samples from 120 allogeneic blood donors collected between Sept 2020 and Dec 2022, including symptomatic and asymptomatic infections, were categorized into 3 groups: SARS-CoV-2 infection followed by COVID-19 vaccination, vaccination followed by breakthrough infection during Delta and Omicron waves, and primary vaccination followed by a booster without infection. Samples were tested with the Vitros IgGQ at 1:20 and/or 1:400 dilution, to increase the test upper range from 200 to either 4000 or 80000 Binding Antibody Units (BAU)/mL*. Samples were also quantified for ancestral (D614G) and variant-specific (Beta, Delta, Omicron) neutralization activity (reporter viral particle neutralization assays). Correlation of results between the Vitros IgGQ and neutralizing antibody (nAb) titers were evaluated, as well as the percent of donations with high nAb titers at >200 BAU/mL and >4000 BAU/mL thresholds.
Results/Findings: With the current FDA- defined CCP qualifying threshold of >200 BAU/mL, of samples collected from vaccine breakthrough infections during the Delta wave 61.7% of donations had nAb titers >1:250 and 51.1% > 1:500. Breakthrough infections during Omicron yielded 80.5% and 73.4% with titers >250 and >500 respectively. Using a threshold of >4000 BAU/mL, during Delta wave 96.7% were >1:250 and 92.2% >1:500. Breakthrough infections during Omicron yielded 97.4% and 94.7% with titers >250 and >500, respectively. There was no difference between individuals with symptomatic or asymptomatic infections, with 57.8% and 58.7% >1:250 at >200 BAU/mL and 96.6% and 100% >1:250 at >4000 BAU/mL, respectively. Conclusions: This study demonstrates that the current FDA threshold of >200 BAU/mL yields high nAb titers (>1:500) in only ~51% to 73% of donations from infected/vaccinated donors. There is no difference in results between donors with symptomatic or asymptomatic infections. Using a threshold of >4000 BAU/mL would yield >92% donations with high nAb titers against ancestral and variant viruses regardless of infection/vaccination or timing status. *dilution not authorized by FDA
Importance of research: Immunocompromised individuals are disproportionately affected by COVID-19 with higher risk of infection and inability to clear the virus. Viral variants have rendered mAbs ineffective, therefore interest in use of COVID-19 convalescent plasma (CCP) has increased. FDA criteria for qualifying CCP may be unnecessarily restrictive and antibody thresholds may be too low to assure high neutralizing antibody titers that would increase the likelihood of successful treatment following variant infections.
