Wild animals show high SARS-CoV-2 exposure linked to human activities

A recent study published in the journal Nature Communications, US researchers analyzed the exposure of 23 wild animal species to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They investigated the impact of human activity and urbanization on seroprevalence. They found the presence of SARS-CoV-2 ribonucleic acid (RNA) in six wild animal species and observed higher seroprevalence in areas with more human activity. Additionally, the researchers identified seven new cases of human-to-animal transmission caused by the omicron variant of the virus.

Prevalence of SARS-CoV-2 RNA and neutralizing antibodies in wildlife communities. Study: Widespread exposure to SARS-CoV-2 in wildlife communities

background

SARS-CoV-2, the cause of COVID-19, has infected over 775 million people worldwide and caused over 7 million deaths. As the virus becomes endemic, more virulent variants pose a major threat. The pandemic has raised concerns that SARS-CoV-2 may infect wildlife and establish a sylvatic cycle, giving rise to new variants. Although infections in captive animals have been previously documented, detection in wild wildlife has been limited mainly to white-tailed deer, wild mink, and Eurasian otters. Experimental infections suggest that many wildlife species can host the virus, but natural infections remain to be thoroughly investigated.

Numerous variants have emerged since 2019 that may be more infectious and impact wildlife. White-tailed deer display a unique virus lineage of human origin, suggesting that deer-to-deer transmission requires minimal adaptation. Once SARS-CoV-2 establishes in wildlife, it may give rise to new mutations that increase virulence, transmissibility, and immune evasion. The adaptation of the virus to a wide range of hosts may make its evolution more unpredictable, complicating vaccine development and creating new challenges for human health. In this study, researchers examined SARS-CoV-2 exposure in various wildlife species in Virginia and Washington DC and assessed the impact of urbanization on seropositivity.

About the Research

SARS-CoV-2 RNA was extracted from nasopharyngeal/oropharyngeal samples from 789 animals from 23 different species. The presence of viral RNA was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Serum samples from six mammalian species (Virginia opossum, raccoon, eastern gray squirrel, white-footed mouse, deer mouse, and one unspecified species) were collected in 2022 and tested for SARS-CoV-2 antibodies using a 60% neutralization cutoff. Serum samples from the pre-2020 and post-2020 eras were compared to assess differences in neutralization. Additionally, the relationship between urbanization (measured by imperviousness) and seroprevalence in wildlife was studied. Human visitation data was used to assess the impact of human activities on seroprevalence.

SARS-CoV-2 sequences were obtained from nasal and oropharyngeal swabs using whole genome sequencing. Pango phylogeny was determined for 12 RNA positive samples and compared with human sequences to identify possible recent introduction into wildlife. Unique mutations in the spike (S) protein were studied using molecular modeling and free energy calculations to understand their impact on protein binding and viral infectivity.

Results and discussion

SARS-CoV-2 RNA was detected in nasopharyngeal samples from six of the total species. Of the 789 samples tested, 23 individuals were found to be positive. Detected individuals included eight deer mice, four Virginia opossums, four raccoons, three cottontail rabbits, three groundhogs, and one eastern long-eared bat. Interestingly, samples collected in the field showed a higher positivity rate (4.04%) compared to the wildlife rehabilitation center samples (2.24%).

Additionally, SARS-CoV-2 antibodies were detected in five of six species (Virginia opossum, raccoon, eastern gray squirrel, white-footed mouse, and deer mouse) collected in 2022. Post-2020 samples had significantly higher neutralization values ​​than pre-2020 samples (p<0.001). Four of the samples were found to exceed the 80% neutralization cutoff.

Furthermore, urbanization was positively correlated with wildlife seroprevalence, and the highest antibody detection rates were found in state parks with high human visitation (80%).Human presence was found to be positively correlated with seroprevalence, which was consistent across different neutralization cutoffs.

Sequences from wildlife included the Omicron sublineage BA.2.10.1 and various XBB* lineages. Notably, these lineages matched lineages circulating among humans at the time, indicating recent human-to-animal transmission. A unique E471V mutation in the receptor-binding domain of the S protein was found to improve binding to the human angiotensin-converting enzyme 2 (ACE2) receptor compared to the canonical BA.2 lineage. Researchers suggest that a unique G798D mutation in the S2 subunit may affect viral entry by affecting glycosylation and structural stability.

Conclusion

In conclusion, this study significantly expands the known range of wild hosts infected by SARS-CoV-2, finding nine species infected with the virus, including six newly recorded species. Species that tested positive, such as mice, rabbits and opossums, display characteristics that may make them better suited to establish SARS-CoV-2 wildlife hosts. These characteristics include a fast-paced life history with early and frequent reproduction, as well as a history of having been hosts to other respiratory viruses.

The findings highlight the need for continued widespread surveillance and detailed ecological studies to fully understand the role of wildlife communities in the transmission and evolution of SARS-CoV-2. Future work should explore the potential contribution of these species to viral persistence and mutation in wildlife, as this could have implications for public health strategies.