#16,318
While SARS-CoV-2 has become over the past couple of years a virus exquisitely suited for humans - it undoubtedly sprang from another reservoir species - most likely bats. We've certainly seen ample evidence of other, SARS-like coronaviruses in bats (see here, here, here, and here), and MERS-CoV is suspected of having a bat origin.
This week, we've more evidence published suggesting a bat origin for COVID, as researchers describe a close cousin to SARS-CoV-2 collected in 2010 from two Rhinolophus shameli bats in Cambodia.
A novel SARS-CoV-2 related coronavirus in bats from Cambodia
Nature Communications volume 12, Article number: 6563 (2021) Cite this article
Abstract
Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010.
Metagenomic sequencing identifies nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a region of the spike, which is not compatible with human ACE2-mediated entry. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously reported, and suggests that Southeast Asia represents a key area to consider for future surveillance for coronaviruses.
(SNIP)
Discussion
The data presented here further indicate that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and likely circulate via multiple Rhinolophus species. Our current understanding of the geographic distribution of the SARS-CoV and SARS-CoV-2 lineages14 possibly reflects a lack of sampling in Southeast Asia, or at least across the Greater Mekong Subregion, which encompasses Myanmar, Laos, Thailand, Cambodia and Vietnam, as well as the Yunnan and Guanxi provinces of China, linking the sampling area of the closest viruses to SARS-CoV-2 identified to date.
Finally, pangolins, as well as members of order Carnivora, especially the Viverridae5, Mustelidae6, and Felidae7 families are readily susceptible to SARS-CoV-2 infection, might represent intermediary hosts for transmission to humans, and should not be ignored in future surveillance efforts in the region. Viruses of the SARS-CoV-2 sublineage, with one exhibiting strong sequence similarity to SARS-CoV-2 in the RBD, were recently detected in distinct groups of pangolins seized during anti-smuggling operations in southeast China6. While it is not possible to know where these animals became infected, it is important to note that the natural geographic range of the pangolin species involved (Manis javanica) also corresponds to Southeast Asia and not China.
Exactly how COVID made the transition from an unknown, probably asymptomatic, bat-borne virus to a deadly human pandemic isn't clear - but as mentioned above - it probably involved an intermediate host (see Science Perspective: The Animal Origin of SARS-CoV-2).
But MERS-CoV - which all evidence suggests is considerable deadlier than COVID - continues to evolve in camels, and its future trajectory is unknown.
While understanding where SARS-CoV-2 originated is important, and might help us prevent another spillover from bats, knowing where it may be going - beyond its initial jump to humans - is equally important.
Should SARS-CoV-2 establish itself in a non-human reservoir - as MERS-CoV has in camels - it could conceivably provide the virus with additional evolutionary pathways, which could potentially reinvigorate or reinvent the pandemic in unpredictable ways in the future.
Very early in the COVID pandemic we saw reassuring research suggesting that SARS-CoV-2 did not readily infect or replicate in many common domesticated animals (see Susceptibility of Ferrets, Cats, Dogs & Other Domestic Animals to SARS-CoV-2 by Dr. Hualan Chen et al.), but cats (and to a lesser extent, dogs) did appear slightly susceptible.
Luckily, pigs, cattle, and poultry appear more-or-less immune to infection, but since the spring of 2020 it became apparent that the virus had a strong affinity for mink, and not only spread like wildfire among farmed mink, it developed unique mutations along the way (see ECDC Rapid Risk Assessment: Detection of New SARS-CoV-2 Variants Related to Mink).
Mink-to-human transmission, which was suspected as early as May of 2020, resulted in a `mink variant' briefly circulating in Denmark (see SSI Study: Denmark's Cluster-5 mink Variant Had Increased Antibody Resistance). Its spread, luckily, was cut short by the arrival of the Alpha, then the Delta variant, against which it could not compete.
Since those early reports, we've seen numerous outbreaks in mink farms around the world, including here in the United States (see USDA APHIS Confirms SARS-CoV-2 in Farmed Mink in Utah), along with concerns that the virus could escape into the wild (see EID Journal: Peridomestic Mammal Susceptibility to SARS-CoV-2 Infection).
Chrissy D. Eckstrand , Thomas J. Baldwin, Kerry A. Rood, Michael J. Clayton, Jason K. Lott, Rebecca M. Wolking, Daniel S. Bradway, Timothy Baszler
Abstract
The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred on five mink farms in Utah and was associated with high mink mortality (35–55% of adult mink) and rapid viral transmission between animals.
The premise and clinical disease information, pathology, molecular characterization, and tissue distribution of virus within infected mink during the early phase of the outbreak are provided. Infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Disease indicators were most notably sudden death, anorexia, and increased respiratory effort.
Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract.
Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strains fell into Clade GH, which is unique among mink and other animal strains sequenced to date. While sharing the N501T mutation which is common in mink, the Utah strains did not share other spike RBD mutations Y453F and F486L found in nearly all mink from the United States. Mink in the outbreak reported herein had high levels of SARS-CoV-2 in the upper respiratory tract associated with symptomatic respiratory disease and death.
(SNIP)
The investigation reveals that mink can spread the virus rapidly between animals and that the disease in mink is associated with viral infection and damage to tissues of the upper and lower respiratory system.
The determination that mink are susceptible to SARS-CoV-2 indicates the need for strict biosecurity measures on mink farms to remediate mink-to-mink and human-to-mink transmission for the protection of mink, as well as prevent potential transmission from mink to humans. It may be prudent for humans working with SARS-CoV-2 mink to wear appropriate PPE until more is understood.
(Excerpt)
Currently, there is no evidence that mink play a significant role in the spread of SARS-CoV-2 to people. However, there is a possibility of mink spreading SARS-CoV-2 to people on mink farms. Mink-to-human spread of SARS-CoV-2 has been reported in the Netherlands, Denmark, and Poland, and new data suggest it might have occurred in the United States.
- Investigations found that mink from a Michigan farm and a small number of people were infected with SARS-CoV-2 that contained unique mink-related mutations (changes in the virus’s genetic material). This suggests mink-to-human spread might have occurred.
- Finding these mutations in mink on the Michigan farm is not unexpected because they have been seen before in mink from farms in the Netherlands and Denmark, and also in people linked to mink farms worldwide.
- To confirm the spread of SARS-CoV-2 from mink to people, public health officials would need more information on the epidemiology and genetics of the virus in mink, mink farm workers, and the communities around mink farms.
- These results highlight the importance of routinely studying the genetic material of SARS-CoV-2 in susceptible animal populations like mink, as well as in people.
While farmed mink have proven to be highly vulnerable to COVID - and represent some risk - they are at least a captive population that can be monitored for the development of dangerous mutations, and culled if needed.
The same can't be said for wild animal populations. And increasingly, we are seeing that some species are readily infected, and can spread the virus easily. Most notably, last July we saw the announcement from the USDA/APHIS: White-Tailed Deer Exposed To SARS-CoV-2 Detected In 4 States,
Again from the CDC:
Research on animals and COVID-19
More studies are needed to understand if and how different animals could be affected by COVID-19.
Many studies have been done to learn more about how this virus can affect different animals. These findings were based on a small number of animals, and do not show whether animals can spread infection to people.
Recent experimental research shows that many mammals, including cats, dogs, bank voles, ferrets, fruit bats, hamsters, mink, pigs, rabbits, racoon dogs, tree shrews, and white-tailed deer can be infected with the virus. Cats, ferrets, fruit bats, hamsters, racoon dogs, and white-tailed deer can also spread the infection to other animals of the same species in laboratory settings.
A number of studies have investigated non-human primates as models for human infection. Rhesus macaques, cynomolgus macaques, baboons, grivets, and common marmosets can become infected with SARS-CoV-2 and become sick in a laboratory setting. There is some evidence suggesting that laboratory mice, which could not be infected with original strains of SARS-CoV-2, can be infected with new virus variants.
Chickens and ducks do not seem to become infected or spread the infection based on results from studies.
Earlier this month, in Two New Reports Find Widespread SARS-CoV-2 In North American Deer, we saw even more evidence of the spread of SARS-CoV-2 in wild deer. There are undoubtedly other susceptible animal hosts for SARS-CoV-2 that haven't been identified, and as the virus evolves, it may expand its range even further.
The availability of multiple non-human animal hosts for SARS-CoV-2 makes the future course of the COVID pandemic unpredictable. We've already seen mink-variants spill back into the human population, there is no reason to assume it can't happen with other host species.
A concern held not only by researchers here, but expressed last September by Chinese scientists in CCDC Weekly Perspectives: COVID-19 Expands Its Territories from Humans to Animals, which warned:
Together with the fact that adaptive mutations are needed when cross-species transmission happens and then circulate among populations of the new host, more efforts are needed to survey the genetic alterations and corresponding impact of transmissibility and infectivity in humans in these novel variants from wild white-tailed deer.
Since SARS-CoV-2 is going wild, many other wild animals would also be infected with SARS-CoV-2 via direct or indirect contact with wild white-tailed deer or even infected patients. Several experimental studies have demonstrated several animals could be susceptible to SARS-CoV-2, such as Egyptian fruit bats (Rousettus aegyptiacus), marmosets (Callithrix jacchus), macaques (Macaca fascicularis and Macaca mulatta), bank voles (Myodes glareolus), and North American deer mice (Peromyscus maniculatus) (10).
However, these are just the tip of the iceberg as the susceptibility of most terrestrial wild animals to SARS-CoV-2 has not been tested.
In addition, the research on susceptibility of marine wildlife (especially marine mammals) to SARS-CoV-2 is still lacking. Due to frequent marine human activities (such as mariculture and marine fishing), the frequency of human contact with marine organisms is high. If some marine organisms are highly susceptible to SAR-CoV-2, there is a risk that SARS-CoV-2 could be transmitted from humans to marine organisms, and worse, SARS-CoV-2 then might spread in the marine ecosystem, which may lead to the generation of some novel SARS-CoV-2 variants with unknown threats to humans.
After the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019, it is now apparent that influenza has a serious competitor in the pandemic arena. And there are other bat-borne viruses out there (think Nipah, Hendra, Ebola, etc.), that may have pandemic potential as well (see Curr. Opinion Virology: Viruses In Bats & Potential Spillover To Animals And Humans).
Ten weeks ago, in PNAS Research: Intensity and Frequency of Extreme Novel Epidemics, we looked at a paper that suggested that the probability of novel disease outbreaks will likely grow three-fold in the next few decades.
All reasons why we need to be preparing for the next pandemic now - because while our current COVID crisis will eventually recede - it is far from the last global health crisis we will face.
