This poster discusses the zoonotic origin of most human infectious diseases and how SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is also believed to have originated from animals. The virus uses the ACE-2 receptor to enter cells, which is well conserved in mammals. There is evidence of infection or exposure to SARS-CoV-2 in 35 non-human animals to date. The virus circulating in largely unmonitored animal species presents an opportunity for viral evolution that could lead to the emergence of novel variants that may spill back to humans. Multiple lines of evidence suggest the Omicron variant may have evolved in rodent populations. The hypotheses we test here are that the most abundant rodent species in the North East of the United States, the White-Footed mouse (Peromyscus leucopus) has been exposed, and/or infected with SARS-Cov-2. We used a commercially available species generic virus neutralization assay (sVNT) to test for exposure and a PCR to determine if there was evidence of active infection of the nasal cavity of P. leucopus. Mice were live captured in the Fall of 2022 at various locations in Central Pa and euthanized in the field to collect blood and the nasal pharyngeal bones were dissected, collected, and preserved in universal transport media under IACUC #46246. All 78 mice were found negative via the sVNT and PCR assays indicating that our sample was not actively infected and had no indication of exposure. However, the emergence of the Omicron variant occurred during our sampling and it has been subsequently determined that the sVNT test would yield false negatives for animals exposed to this new variant due to issues with the Rosetta binding domain utilized in the test. Coupling that P. Leucopus typically only live a few months in the wild and the evidence that wildlife infections mirror those circulating in humans, we suspect our samples would have been exposed to Omicron rather than previous variants. Considering this, our results indicate no exposure to prior variants, but we cannot rule out exposure to Omicron; further testing is needed to determine if this is the case. Surveillance in other common synanthropic wildlife is warranted as the occurrence of spillback from non-human animals has already been demonstrated for four species. Further, the evolution of this type could result in variants for which our current diagnostics and vaccine are ill-prepared. Indeed, the Omicron variant is an N-dropout in standard PCR assays, meaning one of the three targets (the nucleocapsid region) of PCR has already evolved sufficiently to evade current diagnostics.