ABSTRACT
Canine enteric coronavirus (CECoV) variants have an emerging role in severe outbreaks of canine gastroenteritis. Here we used syndromic health data from a sentinel network of UK veterinary practices to identify an outbreak of severe canine gastroenteritis. Affected dogs frequently presented with vomiting, diarrhoea and inappetence. Data from sentinel diagnostic laboratories showed similar seasonal increases in CECoV diagnosis. Membrane glycoprotein (M) gene sequence analysis implied wide geographical circulation of a new CECoV variant. Whole genome sequencing suggested the main circulating 2022 variant was most closely related to one previously identified in 2020 with additional spike gene recombination; all variants were unrelated to CECoV-like viruses recently associated with human respiratory disease. Identifying factors that drive population-level evolution, and its implications for host protection and virulence, will be important to understand the emerging role of CECoV variants in canine and human health, and may act as a model for coronavirus population adaptation more widely.
Subject(s)
Gastroenteritis , DiarrheaABSTRACT
Background: Monkeypox is a zoonotic virus which persists in animal reservoirs and periodically spills over into humans, causing outbreaks. During the current 2022 outbreak, monkeypox virus has persisted via human-human transmission, across all major continents and for longer than any previous record. This unprecedented spread creates the potential for the virus to "spillback" into local susceptible animal populations. Persistent transmission amongst such animals raises the prospect of monkeypox virus becoming enzootic in new regions. However, the full and specific range of potential animal hosts and reservoirs of monkeypox remains unknown, especially in newly at-risk non-endemic areas. Methods: Here, utilising ensembles of classifiers comprising different class balancing techniques and incorporating instance weights, we identify which animal species are potentially susceptible to monkeypox virus. Subsequently, we generate spatial distribution maps to highlight high-risk geographic areas at high resolution. Findings: We show that the number of potentially susceptible species is currently underestimated by 2.4 to 4.3-fold, and that a high density of wild susceptible species are native to Europe. We provide lists of these species, and highlight high-risk hosts for spillback and potential long-term reservoirs, which may enable monkeypox virus to become endemic. Interpretation: We highlight the European red fox and brown rat, as they have established interactions with potentially contaminated urban waste and sewage, which provides a mechanism for potential spillback. We anticipate that our results will enable targeted active surveillance of potential spillback event, to minimise risk of the virus becoming endemic in these regions. Our results also indicate the potential of domesticated cats and dogs (latter now confirmed) being susceptible to monkeypox virus, and hence support many health organisations' advice for infected humans to avoid physical interaction with pets.
ABSTRACT
Molnupiravir is an antiviral approved for treating COVID-19, which is thought to drive lethal error catastrophe. How this drug-induced mechanism of action impacts the emergence of resistance mutations is unclear. AGILE Candidate Specific Trial (CST)-2 is a phase IIa trial randomising 180 adult outpatients with SARS-COV-2 infection within five days of symptom onset to molnupiravir or placebo, with rich serial sampling of nasopharyngeal swabs over 29 days. Viral sequences, that passed genome quality control criteria, from subjects who received molnupiravir (n=59) or a placebo (n=65) were analysed by high-throughput amplicon sequencing. We found evidence that molnupiravir significantly increased the transition/transversion frequency in SARS-CoV-2 in patients, a hallmark of molnupiravir treatment. Over the course of treatment, no consistent, accumulated mutations were identified in either arm.