Abstract
Zoonotic diseases involve pathogen transmission between humans and animals, with most research focused on animal-to-human spillover. However, reverse zoonosis-the transmission of pathogens from humans to animals-remains understudied despite its potential ecological and epidemiological consequences. The SARS-CoV-2 pandemic highlights this risk, as human-associated viruses may sporadically infect wildlife species and generate novel exposure pathways. To assess evidence of SARS-CoV-2 exposure in wildlife, we analyzed serum and rectal swab samples from rodents collected in rural localities of the Yucatan Peninsula, Mexico, between 2021 and 2022. An indirect ELISA detected antibodies against SARS-CoV-2 in 23.1% of sampled rodents. Molecular analysis detected one positive sample with a pan-coronavirus RT-PCR, though all were negative for SARS-CoV-2-specific assays. This study provides serological evidence of SARS-CoV-2 exposure in rodent communities from rural areas of Mexico and is consistent with sporadic wildlife spillback events rather than sustained transmission. The observed exposure patterns may be influenced by human activities and frequent human-wildlife interactions in heterogeneous rural landscapes. Our results underscore the need for integrated serological and genomic surveillance to better understand the ecological context of reverse zoonosis and its implications for public health.