SARS-CoV-2 Cross-Reactivity Can Complicate MERS-CoV Serology

Researchers in the Netherlands evaluated whether antibodies induced by SARS-CoV-2 infection or vaccination could confound serologic identification of past MERS-CoV infection. They tested serum from people with mild COVID-19, intensive care patients with severe COVID-19, and recipients of multiple COVID-19 vaccines, most of whom also had breakthrough infections. Prepandemic samples served as controls. Binding assays and neutralization tests assessed cross-reactivity; the total sample size was not reported in the supplied text.

Cross-reactivity predominantly targeted the conserved MERS-CoV S2 domain. Median S2-binding antibody levels were 67.0 IU/mL after severe COVID-19, 21.0 IU/mL after mild disease, and 17.1 IU/mL in vaccinated participants, compared with 5.4 IU/mL in prepandemic controls. Samples from 11 severe COVID-19 patients neutralized MERS-CoV, and one mild COVID-19 sample partially neutralized it; reported neutralizing titers ranged from 26 to 694.

Only one sample from the SARS-CoV-2–exposed cohorts was positive for both MERS-CoV S1 binding and neutralization. Selected samples tested with a commercial S1 ELISA were all below its positivity threshold. These findings suggest that S1-based screening combined with neutralization can reduce misclassification associated with full-spike or S2-based assays. However, absence of MERS-CoV exposure was assumed from the Dutch setting, and sampling times differed between groups. The early-release article is not yet a final version.