Saturday, March 11, 2023

mBio: SARS-CoV-2 Exposure in Norway Rats (Rattus norvegicus) from New York City

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#17,341

Last November, in SARS-CoV-2 Exposure in Norwegian rats (Rattus norvegicus) from New York City, we looked at a preprint which described evidence of SARS-CoV-2 infection in sewer rats in New York City, and the results of challenge studies using various COVID VOCs on laboratory rats.

Researchers found a relatively high percentage of rats tested had been exposed to the coronavirus, and found that both Delta and Omicron variants can also cause robust infections in Sprague Dawley® rats.

All of this is of concern because NYC is (as are many large cities) home to millions of rats, and any sustained reservoir of SARS-CoV-2 in a non-human host presents the very real risk of seeing a mutated virus evolve and spill back into humans. 

It is not just a theoretical concern, as we've already seen this happen with farmed mink in Denmark in late 2020 (see ECDC Detection of New SARS-CoV-2 Variants Related to Mink), and have seen evidence suggesting both Deer-to-Human and cat-to-human transmission of SARS-CoV-2 virus may have occurred. 

And while unproven, there are some scientists who believe the Omicron Variant may have evolved after the virus jumped to mice or other rodents (see Evidence for a mouse origin of the SARS-CoV-2 Omicron variant), and then spilled back into humans (see also WOAH Statement).

Five months ago, in Preprint: SARS-CoV-2 Infection in Domestic Rats After Transmission From Their Infected Ownerwe saw further evidence of the susceptibility of rodents to COVID, with the author's writing:

We report the transmission of SARS-CoV-2 Omicron variant from a COVID-19 symptomatic individual to two domestic rats, one of which developed severe symptoms. Omicron carries several mutations which permit rodent infection. This report demonstrates that pet, and likely wild, rodents could therefore contribute to SARS-CoV-2 spread and evolution.

Last November's preprint has undergone some minor revisions, and was published late this week by mBio.  You'll find excerpts from the Abstract and study, along with a press release from the American Society For Microbiology below, but you'll want to read the paper in its entirety.   

I'll have a brief postscript after the break.

SARS-CoV-2 Exposure in Norway Rats (Rattus norvegicus) from New York City

Authors: Yang Wang, Julianna Lenoch, Dennis Kohler, Thomas J. DeLiberto, Cynthia Y. Tang , Tao Li, Yizhi Jane Tao , Minhui Guan , Susan Compton, Caroline Zeiss, Jun Hang 5, Xiu-Feng Wan

DOI: https://doi.org/10.1128/mbio.03621-22

ABSTRACT

Millions of Norway rats (Rattus norvegicus) inhabit New York City (NYC), presenting the potential for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to rats. We evaluated SARS-CoV-2 exposure among 79 rats captured from NYC during the fall of 2021. Our results showed that 13 of the 79 rats (16.5%) tested IgG- or IgM-positive, and partial SARS-CoV-2 genomes were recovered from all 4 rats that were qRT-PCR (reverse transcription-quantitative PCR)-positive

Genomic analyses suggest these viruses were associated with genetic lineage B, which was predominant in NYC in the spring of 2020 during the early pandemic period. To further investigate rat susceptibility to SARS-CoV-2 variants, we conducted a virus challenge study and showed that Alpha, Delta, and Omicron variants can cause infections in wild-type Sprague Dawley (SD) rats, including high replication levels in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Additionally, the Delta variant resulted in the highest infectivity.

In summary, our results indicate that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and wild Norway rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the need for further monitoring of SARS-CoV-2 in urban rat populations and for evaluating the potential risk of secondary zoonotic transmission from these rat populations back to humans.

IMPORTANCE 

The host tropism expansion of SARS-CoV-2 raises concern for the potential risk of reverse-zoonotic transmission of emerging variants into rodent species, including wild rat species. In this study, we present both genetic and serological evidence for SARS-CoV-2 exposure to the New York City wild rat population, and these viruses may be linked to the viruses that were circulating during the early stages of the pandemic.
We also demonstrated that rats are susceptible to additional variants (i.e., Alpha, Delta, and Omicron) that have been predominant in humans and that susceptibility to infection varies by variant. Our findings highlight the reverse zoonosis of SARS-CoV-2 to urban rats and the need for further monitoring of SARS-CoV-2 in rat populations for potential secondary zoonotic transmission to humans.

         (SNIP) 

DISCUSSION

Both the serological and molecular data from this study suggest that the rats from NYC were exposed to SARS-CoV-2. Of the tested rats, 16.5% were seropositive, which was higher than the seropositivity rates described in previous reports (11, 12). In addition, 5.1% of these samples were qRT-PCR-positive to SARS-CoV-2, and partial genomes were recovered from all samples which were qRT-PCR-positive for SARS-CoV-2. Genomic analyses suggest that the viruses detected from the collected Norway rats were associated with the B-lineage virus, which was predominant in NYC during the early stages of the pandemic.

We speculate that these B-lineage viruses are enzootic in rat populations after being introduced to the NYC rat populations during the early stages of the pandemic, or that rats could have been exposed to the B-lineage viruses present in unknown sources. This is supported by a recent study reporting that the Wuhan-Hu-1-like virus can infect SD rats (17), although an earlier study showed that the prototype Wuhan-Hu-1-like SARS-CoV-2 could not infect SD rats (6). Such a discrepancy may be due to additional mutations in the challenge Wuhan-Hu-1-like strains or genetic variations in the SD rats used in these studies.

Thus, further surveillance is needed to understand the virological prevalence in NYC rats, particularly for several emerging variants with high infectivity among rats, including those that circulated in NYC during the past 2 years of the COVID-19 pandemic.

          (Continue . . . ) 

The accompanying news release from the ASM follows:

Study shows New York City rats carry SARS-CoV-2
Peer-Reviewed Publication

AMERICAN SOCIETY FOR MICROBIOLOGY

Washington, DC -- A new study has demonstrated that rats are susceptible to infection with Alpha, Delta and Omicron variants of SARS-CoV-2 and wild rats in the New York City municipal sewer systems and elsewhere in the city have been exposed to SARS-CoV-2. The study was published in mBio, an open-access journal of the American Society for Microbiology. 

“Our findings highlight the need for further monitoring of SARS-CoV-2 in rat populations for potential secondary zoonotic transmission to humans,” said study principal investigator Henry Wan, Ph.D., Professor and Director of the Center for Influenza and Emerging Infectious Diseases at the University of Missouri. “Overall, our work in this space shows that animals can play a role in pandemics that impact humans, and it’s important that we continue to increase our understanding so we can protect both human and animal health.” 

Rats are widely distributed in urban communities in the United States. For example, New York City alone has approximately eight million wild rats. These wild rats have ample opportunities to interact with humans. Two previous studies suggested that rats in Asia (Hong Kong) and Europe (Belgium) were exposed to SARS-CoV-2; however, it is unknown which SARS-CoV-2 variant these rats were exposed to in both studies. 

In the new study, the researchers set out to determine whether the SARS-CoV-2 virus in humans has been transmitted to the rat population in urban areas of the United States, specifically New York City, and if so, which SARS-CoV-2 variant caused those infections. The researchers also set out to determine whether (and which) SARS-CoV-2 variants in NYC can cause infections in rats. 

“In Fall of 2021, U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) sampled Norway rats (Rattus norvegicus) in New York City to look for evidence of SARS-CoV-2 infection,” said study coauthor Tom DeLiberto, D.V.M., Ph.D., SARS-CoV-2 Coordinator at USDA APHIS Wildlife Services. “Two trapping efforts were conducted during September and November with permission from the NYC Department of Parks and Recreation in and around locations surrounding wastewater systems. Most of the rats were trapped in city parks within Brooklyn, although some were captured near buildings outside of park boundaries.” 

Biologists collected and processed samples from 79 rats for virological studies and genomic sequencing. The researchers found that the rats were exposed to SARS-CoV-2 and showed a possible link to the viruses that were circulating in humans during the early stages of the COVID-19 pandemic. Specifically, 13 of 79 rats (16.5%) tested positive. “To the best of our knowledge, this is one of the first studies to show SARS-CoV-2 variants can cause infections in the wild rat populations in a major U.S. urban area,” Dr. Wan said. 

To further investigate rat susceptibility to SARS-CoV-2 variants, the researchers conducted a virus challenge study and showed that Alpha, Delta and Omicron variants (variants found in humans) can cause infections in rats (wild-type Sprague Dawley rats), including high replication levels in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Susceptibility to infection varied by type of variant. 

“Our findings highlight the need for further monitoring of SARS-CoV-2 in rat populations to determine if the virus is circulating in the animals and evolving into new strains that could pose a risk to humans,” Dr. Wan said. “SARS-CoV-2 virus presents a typical one-health challenge which requires collaborative, multisectoral and transdisciplinary approaches to fully understand such challenges.”

While farmed mink, deer, and rats have taken center stage, we recently looked at the growing list of susceptible non-human hosts in Nature: Comparative Susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV Across Mammals.


How often SARS-CoV-2 infects animals in the wild is largely unknown, but the USDA has confirmed over 400 instances across a wide variety of mammals. 

Spillover of the virus into other species is increasingly viewed as a serious threat (see WHO/FAO/OIE Joint Statement On Monitoring SARS-CoV-2 In Wildlife & Preventing Formation of Reservoirs). 

While we appear to be tantalizingly close to moving into a post-pandemic phase with COVID, the emergence of a new, more dangerous variant from a non-human reservoir could prove to be a serious setback for the world.