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Not quite a year ago, on March 24th 2024, we looked into Curious Reports of Unknown Disease In Dairy Cows (Texas, Kansas & New Mexico). Reports that the following day would be confirmed as being HPAI H5 (see USDA Statement on HPAI In Dairy Cattle in Texas & Kansas Herds).
Prior to this point, while cattle had been experimentally infected in the lab, they were thought poorly susceptible to influenza A viruses (see A Brief History Of Influenza A In Cattle/Ruminants). Cattle, however, are susceptible to influenza D viruses.
Although originally believed to be a geographically limited spillover with limited impact, today we know nearly 1,000 herds across 17 states have been infected (an undercount), and that at least 41 humans have been infected via exposure to infected cattle, along with a large number of peridomestic mammals.
While it is too soon to know how much of an impact it may have, a year later we have a eerily similar report - this time on a novel coronavirus - detected among beef cattle in Monterrey, Mexico.
Coronaviruses are divided into 4 distinct genera; Alphacoronaviruses, Betacoronaviruses, Gammacoronaviruses, and Deltacoronaviruses - and while both birds and mammals are susceptible to coronavirus infection - they each (at least, for the most part) stay in their own lane.
Birds are primarily infected by gammacoronaviruses, such as infectious bronchitis virus (AIBV) and occasionally by deltacoronaviruses, while mammals are primarily affected by alphacoronaviruses and betacoronaviruses.
Porcine deltacoronavirus (PDCoV), first identified in 2012, is one of those DCoV outliers we keep an eye on (see PNAS: Broad Receptor Engagement of PDCoV May Potentiate Its Cross-Species Transmissibility) due to its feared zoonotic potential (see also New pig virus found to be a potential threat to humans).
Which is why, when dealing with viruses, one never likes to say `never'.
Cattle are highly susceptible to a Bovine coronavirus (BCov) - a betacoronavirus - which causes both respiratory and gastrointestinal diseases (see Frontiers Bovine Coronavirus and the Associated Diseases), which was first isolated by the University of Nebraska in 1972.But the coronavirus described in the following report is an alphacoronavirus - and while the entire genome has not been sequenced - it most closely resembles a rodent-coronavirus isolated in China in 2021 (see AFD blog Nature: Virus Diversity, Wildlife-Domestic Animal Circulation and Potential Zoonotic Viruses of Small Mammals, Pangolins and Zoo Animals).
Novel Rodent Coronavirus-like Virus Detected Among Beef Cattle with Respiratory Disease in Mexico
by Ismaila Shittu 1,†ORCID,Judith U. Oguzie 1,†ORCID,Gustavo Hernández-Vidal 2ORCID,Gustavo Moreno-Degollado 2,Diego B. Silva 1,Lyudmyla V. Marushchak 1,Claudia M. Trujillo-Vargas 1,John A. Lednicky 3,4ORCID andGregory C. Gray 1,5,6,7,*
Viruses 2025, 17(3), 433; https://doi.org/10.3390/v17030433 (registering DOI)
Submission received: 12 February 2025 / Revised: 13 March 2025 / Accepted: 14 March 2025 / Published: 18 March 2025
Abstract
In February 2024, while conducting surveillance for novel respiratory viruses, we studied four beef cattle farms near Monterrey, Mexico. Nasal swabs were collected from sick and healthy beef cattle along with 3 h aerosol samples. None of the samples had molecular evidence of influenza A viruses. Three (8%) of thirty-six nasal swabs collected from the four farms and four (33.3%) of the twelve bioaerosol specimens had molecular evidence of influenza D virus.Five sick cow nasal swabs and one bioaerosol sample on a single farm had molecular evidence of rodent coronavirus-like (RCoV), an alphacoronavirus. Three (60%) of the five RCoV-positive cattle nasal swabs also had molecular evidence of influenza D. Attempts to isolate the RCoV in Vero-E6, LLC-MK2, MDBK, and L-2 cells were unsuccessful. However, we were able to assemble ~60% of the RCoV genome using next-generation sequencing.The six RCoV-positive samples clustered with RCoV strains identified in China in 2021. During the last 12 months, we have studied an estimated 478 dairy and beef cattle nasal swabs on 11 farms in the US and Mexico, and these RCoV detections are the first we have encountered. While feed contamination cannot be ruled out, given the propensity of CoVs to jump species and that we detected RCoV only in the noses of sick cows on this one farm, we are concerned that these findings could represent an isolated RCoV spillover event. With this report, we are alerting veterinarians and cattle farm owners of our observations that RCoV may be a new cause of bovine respiratory disease.
(SNIP)
Discussion
Since the beginning of this century, a number of novel coronaviruses (CoVs) have emerged to cause epizootics among humans [21]. The largest human epidemic was the pandemic caused by SARS-CoV-2, which, since 2019, has resulted in an estimated 776 million human illnesses and approximately 7 million deaths globally (as of December 2024) [22].
In previous active surveillance of spillover events, our research teams documented human influenza viruses and enteroviruses in pigs [23,24], influenza D virus among poultry [25], vampire bat-like enteroviruses among humans [26], among others. Recently, we isolated and cultured a novel canine coronavirus (CCoV-HuPn-2018) in nasopharyngeal swab samples from hospitalized pneumonia patients in Sarawak, Malaysia [27].
In this study, we found evidence of a very similar RCoV in the nasal swabs of five sick beef cows and one farm aerosol specimen in a single beef cattle farm near Monterrey, Mexico. To the best of our knowledge, this represents the first evidence of RCoV in sick cattle.
It is important to note that RCoV, an alphacoronavirus, is distinct from bovine coronavirus (a betacoronavirus), which is commonly associated with respiratory infections in cattle. While this finding might be explained by rodent-contaminated feed, we did not find molecular evidence of this virus in the healthy cattle we studied from the same and other farms during this sampling period.Additionally, among more than 350 nasal swabs we collected from sick cattle on 11 other US and Mexican farms during the period March 2024 to January 2025, RCoV was only detected in the sick cows on this one farm. Hence, we hypothesize that the detected RCoV contributed to the respiratory illnesses in the studied cattle. Previous reports have shown the phylogenetic clustering of RCoVs with those from bats [28] and alphacoronaviruses from rodents with rabbits [29], suggesting cross-species transmission. The RCoV in this study grouped with RCoV sequences previously detected and reported in China [28], suggesting a common source. It has been shown that RCoVs have a common origin and only change over time via co-divergence with various hosts and interspecies transmission [30].Additionally, we noted that 60% of the cattle nasal swabs with molecular evidence of an RCoV also had molecular evidence of influenza D virus. As far as we know, this is the first evidence of a co-infection involving both rodent coronavirus and influenza D.
These observations are concerning as they may represent a newly recognized CoV spillover event. Our study is limited because we could not obtain a virus isolate or assemble a complete genome for better insight into RCoV characteristics. We also did not have a way to examine cattle sera for evidence of infection with the RCoV. During the COVID-19 pandemic, caused by the SARS-CoV-2 virus, several studies reported evidence of coronaviruses including alphacoronaviruses in rodents, suggesting their exposure to these viruses [31,32,33].
Rodents are estimated to constitute more than 40% of all mammalian species, and some are known to carry zoonotic pathogens. However, until recently, there have been sparse studies of coronaviruses among rodents [34]. It seems prudent to conduct future surveillance for novel coronaviruses among sick livestock. If RCoVs or other novel viruses are prevalent among sick cattle, we need to confirm whether they are pathogenic and then better understand their epidemiology with the goal of preventing their transmission. In summary, our findings underscore the importance of surveillance for novel viruses at the animal–human interface as part of pandemic preparedness.
While we grudgingly accept that zoonotic influenza pandemics may occur several times a century, there seems to be a widespread belief that our SARS-CoV-2 pandemic was somehow a rare - one off - event, that is unlikely to be repeated.
The reality is that coronaviruses are highly mutable, and have the potential to recombine into new variants, which raises concerns over the co-circulation of SARS-CoV-2 along with MERS-CoV, and many other coronaviruses (see Nature: CoV Recombination Potential & The Need For the Development of Pan-CoV Vaccines).This despite two other `close calls' with `COVID-like' epidemics in the past 23 years (SARS & MERS), and the fact that new emerging coronavirus threats continue to be discovered (see J. Med. Virology: Potential Cross-Species Transmission Risks of Emerging Swine Enteric Coronavirus to Human Beings).
Nature: Study on Sentinel Hosts for Surveillance of Future COVID-19-like Outbreaks
Preprint: Human Cell adaptation of the Swine Acute Diarrhea Syndrome Coronavirus Spike Protein
Cureus: Circulation of Non-(MERS) Coronaviruses in Imported Camels in Saudi Arabia
Preprint: Emergence & Spread of SARS-CoV-2 Variants from Farmed Mink to Humans and Back - Denmark, June-November 2020.
Systematic Review: SARS-CoV-2 Infection in Animals - Patterns, Transmission Routes, and Drivers
While we've been primarily focused on avian H5 viruses this year, this is a reminder than Nature's laboratory is not only open 24/7, it is fully capable of running multiple GOF (Gain of Function) field experiments concurrently.
We now live in an age (see The Third Epidemiological Transition) where the the number, frequency, and intensity of pandemics are only expected to increase over the next few decades.
BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover EventsWhile we can debate when - or from what - another pandemic is inevitable. All we can really control is how well prepared we are, when the inevitable happens.
PNAS Research: Intensity and Frequency of Extreme Novel Epidemics