Cross-reactivity mediated by SARS-CoV-2 antibodies: Mechanism and impact of elevated HIV ELISA false-positive rates in the late-phase COVID-19 pandemic

Abstract

This study analyzed the correlation between false-positive HIV ELISA results (using Bio-Rad reagents) and SARS-COV-2 antibody levels in 301 unpaid apheresis platelet donors with prior infection or vaccination, enrolled from Zhejiang Blood Center between February 1 and May 31, 2023. Trends in both the HIV ELISA false-positive rate and SARS-COV-2 antibody levels were assessed. The false-positive rate rose in early 2023, peaking at 0.68 % in mid-February, before gradually declining to the historical baseline of approximately 0.1 % by May's end. Similarly, donor SARS-COV-2 antibody levels peaked in February and subsequently decreased. Correlation analysis revealed a strong positive correlation (P<0.01) between HIV ELISA false-positive rates and SARS-CoV-2 antibody levels. The findings indicate a positive correlation, suggesting antibody cross-reactivity, likely mediated by structural similarities and shared epitopes between SARS-CoV-2 spike proteins and HIV-1 antigens (especially the p24 antigen in fourth-generation assays). The study recommends that significant fluctuations in false-positive rates warrant investigation into specific causes, including reagent issues. These findings underscore the need for continuous monitoring of false-positive results in HIV screening during pandemics. Improving reagent specificity and implementing rapid donor re-entry procedures are essential to safeguard blood supply efficiency and maintain donor trust.