Saturday, December 19, 2020

EID Journal: Susceptibility of Domestic Swine to Experimental Infection with SARS-CoV-2

#15,634

When SARS-CoV-2 (presumably) jumped from bats to humans, it could have done so either directly (see graphic above) or via an intermediate host. Several potential intermediate hosts have been identified (see EID Journal: Susceptibility of Raccoon Dogs for Experimental SARS-CoV-2 Infection) but so far, the exact route of this novel coronavirus to becoming a pandemic remains unknown. 

Once SARS-CoV-2 jumped species to infect and transmit readily between humans, the search for other susceptible species was launched. Not only would additional reservoir species make the virus harder to control or eradicate, it could also provide the virus with additional evolutionary paths to follow. 

The two biggest concerns were companion animals (primarily dogs and cats), and farmed livestock.  Should SARS-CoV-2 flourish in poultry, or pigs, or cattle - or in household pets - then the COVID-19 pandemic would become much harder to deal with. 

And since a variety of other coronaviruses are known to infect, and transmit efficiently, among birds (IBV), swine (PED & TGE), cattle (BCoV), and cats (FID), these concerns were taken seriously. 

While we saw some early reports of household pets infected with the virus (see Hong Kong AFCD: Dog Tests `Weakly Positive' For COVID-19 and Pet cat tested positive for COVID-19), initial lab experiments were encouraging.

In early April, in Susceptibility of Ferrets, Cats, Dogs & Other Domestic Animals to SARS-CoV-2Dr. Hualan Chen - one of the world's most respected virologists - and director of China's National Avian Influenza Reference Laboratory, published a paper on the susceptibility of a variety of animals to the SARS-CoV-2.


Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2
Hualan Chen et al.
doi: https://doi.org/10.1101/2020.03.30.015347

         (Excerpt)

We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but efficiently in ferrets and cats. We found that the virus transmits in cats via respiratory droplets. Our study provides important insights into the animal reservoirs of SARS-CoV-2 and animal management for COVID-19 control.

          (Continue . . . )
 

While cats have not been shown to transmit the virus efficiently to others, the same cannot be said for mink - which are close relatives of ferrets - which have proven themselves quite susceptible to the virus.  

As mink transmit the virus, over time SARS-CoV-2 can `adapt' to its new host, and new mutations can emerge (see Preprint: Recurrent Mutations in SARS-CoV-2 Genomes Isolated from Mink Point to Rapid Host-Adaptation) as illustrated in the serial passage graphic below.

So far, mink appear to be the biggest non-human reservoir of the virus, but there are many other mammals that have yet to be adequately tested. And some of the early reassuring test results on livestock are being repeated, since the virus continues to evolve. 

All of which brings us to a new EID Journal research report - which finds that while swine are nowhere near as susceptible to our pandemic coronavirus as mink or humans - they may be a bit more susceptible to SARS-CoV-2 infection than initially thought. 

This is a lengthy, detailed, report and so I've only posted the Abstract and Discussion.  Follow the link to read the full report.   I'll have a postscript when you return. 


Volume 27, Number 1—January 2021
Research
Susceptibility of Domestic Swine to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2
Brad S. Pickering , Greg Smith, Mathieu M. Pinette, Carissa Embury-Hyatt, Estella Moffat, Peter Marszal, and Charles E. Lewis

Author affiliations: University of Manitoba, Winnipeg, Manitoba, Canada (B.S. Pickering); Canadian Food Inspection Agency, Winnipeg (B.S. Pickering, G. Smith, M.M. Pinette, C. Embury-Hyatt, E. Moffat, P. Marszal); Iowa State University, Ames, Iowa, USA (B.S. Pickering, C.E. Lewis)


Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease, has been shown to infect several species. The role of domestic livestock and associated risks for humans in close contact with food production animals remains unknown for many species. Determining the susceptibility of pigs to SARS-CoV-2 is critical to a One Health approach to manage potential risk for zoonotic transmission.
 
We found that pigs are susceptible to SARS-CoV-2 after oronasal inoculation. Among 16 animals, we detected viral RNA in group oral fluids and in nasal wash from 2 pigs, but live virus was isolated from only 1 pig. Antibodies also were detected in only 2 animals at 11 and 13 days postinoculation but were detected in oral fluid samples at 6 days postinoculation, indicating antibody secretion. These data highlight the need for additional livestock assessment to determine the potential role of domestic animals in the SARS-CoV-2 pandemic

         (SNIP)

Discussion
Our study found that domestic swine are susceptible to low levels of SARS-CoV-2 viral infection. Among 16 experimentally inoculated animals, 5 (31.3%) displayed some level of exposure or elicited an immune response to the virus. Only 1 pig in our study retained live virus, but 2 other animals had detectible RNA measured in nasal wash, and another 2 developed antibodies. One pig (20–06) displayed mild, nonspecific clinical signs, including coughing and depression. Then, over the 9 days between cessation of clinical signs and postmortem evaluation, we found this pig maintained the virus in the submandibular lymph node, but virus was undetected in other samples from this animal. In addition, multiple pigs demonstrated mild ocular and nasal discharge that appeared during the immediate, postinfection period. Of note, among 5 animals with potential infection, we detected only low levels of viral RNA; no live viral shedding was identified.
After detection of viral RNA in group oral fluids collected by rope chews at 3 dpi, we detected secreted antibody by using sVNT; we detected viral RNA in the same sample type at 6 dpi. The amount of antibody measured in oral fluids from swine would be considered below a protective cutoff based on comparisons to classical neutralizing titers, however the discovery of secreted antibody in oral fluids might be useful for surveillance efforts. This finding also demonstrates the possibility that human saliva should be evaluated as a less invasive method to provide accompanying evidence with serosurveillance studies for exposure to SARS-CoV-2.
The results of this study contradict previous reports indicating swine are not susceptible to SARS-CoV-2 infection (4,36). Previous studies did not detect RNA in swabs or organ samples, and no seroconversion was measured. Infectious dose, viral isolate, age, and breed or colony of swine could affect study outcomes. Of note, we used a 10-fold higher viral dose for experimental infection than was used in previous studies. Moreover, we obtained animals from a high health status farm in Manitoba, rather than a specific pathogen–free colony, to determine the risk to farmed pigs in Canada.
Altogether, these findings indicate that further investigations into the susceptibility of additional domestic livestock species should be conducted to assess their risk for infection and zoonoses. Finally, we emphasize that to date no SARS-CoV-2 cases among domestic livestock have been documented by natural infection; however, the results of this study support further investigations into the role that animals might play in the maintenance and spread of SARS-CoV-2.
This article preprinted at https://biorxiv.org/cgi/content/short/2020.09.10.288548v1External Link.
Dr. Pickering is the head of the Special Pathogens Unit at the National Centre for Foreign Animal Disease with the Canadian Food Inspection Agency. His research focuses on high consequence pathogens including both emerging and reemerging zoonotic diseases of veterinary importance.
Author contributions: B.P. conceived the research. B.P, G.S., M.M.P., E.M, P.M., and C.E.L. performed the experiments. B.P, G.S., M.M.P., C.E.H., and C.E.L. analyzed the data. B.P. wrote the manuscript with input from B.P, G.S., M.M.P., E.M., and C.E.L. All authors discussed the results and reviewed the manuscript.

While it is important to note that no natural infection of swine by SARS-CoV-2 has been reported, the fact that pigs - which are raised in large herds held in very close quarters - can be experimentally infected (even if only weakly) is the kind of opening the virus might someday be able to take some advantage. 

The serial passage study, described above, shows how - over time - a poorly adapted virus can become better adapted to a new species as it moves through a series of hosts.  It doesn't have to happen, but it can. 

Whether that will happen down the road with SARS-CoV-2 in swine (or other species) is unknown - but we've already seen it happen in mink - and so the risks of seeing additional species jumps for COVID-19 are not zero. 

Like it or not, SARS-CoV-2 is not a static threat - it is a moving target that must navigate an often hostile environment - and either adapt or pivot if it is to survive. Hopefully, it will flounder in the face of increasing community immunity and the release of more vaccines, and in time recede. 

But it is far to soon to assume we've seen the last surprise offered up by this pandemic virus.  Making it important to confirm that what we believed was true months ago, remains true today.