Serological analysis of COVID-19 patients highlights cross-reactivity of antibodies with the HIV-1 2F5 epitope.

The Coronavirus disease 2019 (COVID-19) pandemic has raised concerns regarding the specificity of serological assays due to potential antibody cross-reactivity. In this study, we analyzed sera from 57 individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using enzyme-linked immunosorbent assay (ELISA) to assess antibody recognition of a human immunodeficiency virus type 1 (HIV-1) envelope epitope (2F5). Cross-reactive binding to the HIV-1 antigen was detected in 38.5 % (22/57) of samples, indicating nonspecific antibody recognition. Interestingly, sera from HIV-1-infected individuals and the monoclonal anti-2F5 antibody exhibited no reactivity toward the SARS-CoV-2 Spike receptor-binding domain (RBD), indicating that cross-reactivity occurs in a unidirectional manner and does not compromise the specificity of RBD-based diagnostic assays. These findings support the specificity of RBD-targeted assays and advocate for careful interpretation of HIV-1 serological assays in individuals with recent SARS-CoV-2 infection, particularly where dual circulation occurs.