SARS-CoV-2 was detected between January and March 2021 in more than a third of deer living in freedom in northeastern Ohio (state in the Midwestern United States), reports a study posted on December 23, 2021 on the journal’s website Nature. The species of cervid in question is called “white-tailed deer” (Odocoileus virginianus). It appears that SARS-CoV-2 can be transmitted between infected deer and acquire new mutations in its protein spike. These results raise important questions about the future of the evolutionary trajectory of the virus, deer potentially constituting a new animal reservoir for the virus responsible for Covid-19.
This study, led by veterinarians from the University of Cleveland (Ohio), reports that SARS-CoV-2 was detected by RT-PCR in nasal swabs in a large proportion of white-tailed deer. More specifically, SARS-CoV-2 was detected in 129 of the 360 cervids tested, ie in more than 35% of them. Researchers at the University of Cleveland consider it “alarming” that more than a third of the deer in their study were found positive for SARS-CoV-2 by PCR, suggesting the existence of an active viral infection or recent.
This rate of 35% of infected deer is comparable to that reported by another American team last November. SARS-CoV-2 RNA was detected by RT-PCR test in 94 retropharyngeal lymph nodes (located behind the pharynx) out of 283, ie in more than 33% of the cervids tested.
Posted last November on the prepublication site medRxiv, this study focused on biological samples taken in several regions of Iowa between April 2020 and January 2021, from deer living in the wild and in captivity. Molecular virologists then observed that the genetic sequences belonged to several viral lines and that these corresponded to those circulating in humans at the time.
The new study, carried out on deer in the state of Ohio, therefore confirms the results presented last November which, in turn, concerned deer living in the state of Iowa.
By showing the presence of the virus by PCR, these two recent studies go further than a serological study published in August 2021 in the Proceedings of the American Academy of Sciences. (PNAS). It had reported that 40% of blood samples taken in 2021 from white-tailed deer in four states (Michigan, Pennsylvania, Illinois, New York) contained anti-SARS-CoV-2 antibodies.
“Serological tests are known to be difficult to interpret and many animal health experts hoped these results were only an artifact. Unfortunately, our study suggests that the antibodies seen in deer in other states could be the result of active infection, and that this is only the tip of the iceberg ”, can we read in the newly published article in Nature.
After infected deer in Iowa, those in Ohio
The new study was conducted with deer living at nine separate sites in the state of Ohio. It indicates that the prevalence varied depending on the location from 13.5% to 70%. The highest prevalence was observed in four sites located near urban areas with high human population density. The RT-PCR test was significantly more likely to be positive for SARS-CoV-2 in male deer and larger deer.
The results show that deer, roaming free in six locations in northeastern Ohio, were infected with three variants of SARS-CoV-2, namely B.1.2, B.1.582 and B.1.596. These viruses do not belong to the Alpha or Delta lineages.
It is recalled that in the United States the Alpha and Delta variants did not become widely distributed until after February 2021. The collection of samples took place during the six weeks after the peak of the epidemic in winter 2020-2021. At that time, the B.1.2 virus was dominant in the Ohio population, making up over 50% of SARS-CoV-2 viruses at that time. This virus was detected in deer living at four of the nine sites analyzed. The minority variant B.1.596 has been identified at another site. An even rarer variant, B.1.582 (present in approximately 1% of human samples) was detected at an even different site.
Vanessa Hale, Andrew Bowman and their veterinary colleagues at the University of Cleveland (Ohio) also report data on the genetic sequence of isolated SARS-CoV-2. It appears that six human-to-deer transmission events were observed, linked in one site to the B.1.596 virus, in another to B.1.582 and six others to B.1.2.
Viable SARS-CoV-2 virus (B.1.582) was isolated from deer in two nasal swabs, indicating that naturally infected cervids harbor infectious virus.
Unusual SARS-CoV-2 mutations in deer
Transmission between cervids was analyzed by focusing on the occurrence of seven clustered cases linked to the B.1.596 virus. It turns out that unusual mutations have been detected in the viruses detected during this cluster in deer. These mutations, responsible for an amino acid change, have not been observed in humans in most closely related SARS-CoV-2 viruses. Au total, six mutations* present in deer are unusual in humans as they are only found in less than 0.05% of the genomic sequences analyzed.
In other infected deer living at separate sites and not part of a cluster, unusual amino acid changes were observed in the S1 subunit of the protein. spike. A B.1.2 virus carried the H245Y mutation in the amino-terminal domain (NTD) of the protein spike. A B.1.596 virus contained a mutation (E484D) in a key region of the protein spike, in this case the receptor binding domain (RBD, receptor binding domain) which interacts directly with the ACE2 receptor present on the cells that the virus infects.
These two mutations (H245Y and E484D) identified in SARS-CoV-2 from deer appear to be relatively rare in human SARS-CoV-2 isolates. They were found in less than 0.5% of all SARS-CoV-2 detected in humans. The E484D mutation has in fact only been detected worldwide in 201 genomic sequences of SARS-CoV-2 and in only 71 sequences from the United States. Finally, to date, none of the human B.1.596 viruses has been found to carry this mutation present in the B.1.596 deer virus. At this stage, it is therefore not possible to say whether this mutation appeared spontaneously in deer (mutation again) or if it could have been exceptionally transmitted from man to deer.
Possibilities for the virus to evolve in a new animal reservoir
All of these results therefore indicate that the white-tailed deer (white-tailed deer, literally white-tailed deer) potentially constitutes a new reservoir for SARS-CoV-2. These deer could in turn transmit the virus to other wildlife species.
The study published in Nature also shows that new mutations, very few observed in human viral isolates, have been detected in deer, including one located in the receptor binding domain. According to the authors, such mutations can potentially be amplified in a new animal reservoir in which high infection rates and different constraints in terms of genetic evolution are observed. A potential threat must therefore be raised: the possibility that SARS-CoV-2 from deer, in particular new variants, succeed in crossing the species barrier in the opposite direction, in other words from deer to man. We then speak of reverse zoonosis (spillback in English).
“No spillback was observed, but these results demonstrate that SARS-CoV-2 viruses have the capacity to diffuse in wildlife in the United States, potentially opening new avenues of evolution”, say the authors. And to add that“There is an urgent need to expand surveillance for SARS-CoV-2 viruses in potential wild hosts, document the scale of the problem in white-tailed deer nationwide, understand the ecology of transmission and follow evolutionary trajectories in the future, including in other potential host species ”.
Need for a comprehensive ‘One Health’ approach
Veterinary researchers recall that approximately 30 million white-tailed deer roam free in suburban, rural and urban areas across the United States. Ohio has more than 700,000 free-roaming white-tailed deer, plus 440 commercial deer farms.
The authors point out that“There is a lot of fodder available around urban and suburban residences in gardens and plantations, which attracts deer close to humans and their pets. It is therefore not surprising that deer in urban sites had a higher risk of infection in our study ”.
According to them, urban environments offer many opportunities for deer to come into direct and indirect contact with sources contaminated by humans (waste, bait, in particular), which can serve as viral transmission routes to wildlife. In addition, water pipes in the urban and suburban environment can be contaminated as SARS-CoV-2 is excreted in the stool and can end up in wastewater.
It remains to be seen how the virus is transmitted between deer. Deer are social animals that live in small herds and touch each other’s muzzles. The authors believe that it is difficult to determine whether the baits (whole grain corn) used to attract deer to a site, as part of a deer population regulation program or during hunting activities, may have facilitate the transmission of the virus to these wild animals. It should be noted that deer infected with SARS-CoV-2 seem to remain largely asymptomatic. In any case, this is what was observed on very small numbers during two experimental studies.
This new study reminds, once again, that the states of health of the human population and of animals are strongly linked. Hence the concept of One Health (One health). “There is an urgent need to establish comprehensive ‘One Health’ programs to monitor deer, the environment and other wildlife hosts around the world,” conclude the veterinarians, authors of the article.
Marc Gozlan (Follow me on Twitter, Facebook, LinkedIn)
* Were observed in ORF1ab: a deletion of 5 residues in nsp1 (∆82-86) and four mutations: nsp2_T434I, nsp2_P597L, nsp12_A382V, nsp13_M474I. A deletion (loss of genetic material, ∆141-144) was also detected in the S1 subunit of the protein spike in the seven SARS-CoV-2 viruses involved in this animal cluster.
To know more :
Hale VL, Dennis PM, McBride DS, et al. SARS-CoV-2 infection in free-ranging white-tailed deer. Nature. 2021 Dec 23. doi: 10.1038/s41586-021-04353-x
Chandler JC, Bevins SN, Ellis JW, et al. SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus). Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2114828118. doi: 10.1073/pnas.2114828118
Kuchipudi SV, Surendran-Nair M, Ruden RM, et al. Multiple spillovers and onward transmission of SARS-Cov-2 in free-living and captive White-tailed deer (Odocoileus virginianus). bioRxiv. Posted November 01, 2021. doi: 10.1101/2021.10.31.466677
Cool K, Gaudreault NN, Morozov I, et al. Infection and transmission of SARS-CoV-2 and its alpha variant in pregnant white-tailed deer. bioRxiv. 2021 Aug 16:2021.08.15.456341. doi: 10.1101/2021.08.15.456341
Palmer MV, Martins M, Falkenberg S, et al. Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2. J Virol. 2021 Mar 10;95(11):e00083-21. doi: 10.1128/JVI.00083-21
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