Researchers from MRC-University of Glasgow Centre for Virus Research – Scotland and the School of Biodiversity at the University of Glasgow – Scotland are warning based on their study findings that domestic cats are increasing contracting circulating SARS-CoV-2 variants from human and that they could end up being viral reservoirs that can also lead to the emergence of more worrisome variants or recombinant variants that could be disastrous for humans.
The study findings were published on a preprint server and are currently being peer reviewed.
Throughout the COVID-19 pandemic, there have been sporadic cases of SARS-CoV-2 infection detected in felids, particularly in domestic cats (1, 2, 3, 4, 5). SARS-CoV-2 infections in domestic cats have been reported in the UK (6, 7) and over 20 other countries worldwide, with global spread likely to be considerably greater.
Infections have also been reported in several other felids including snow leopards, lions, tigers and fishing cats (4, 8). The ACE2 receptor molecule that facilitates SARS-CoV-2 cell entry is well conserved across many mammalian species (9, 10). The amino acid sequence of the ACE2 protein of Felis catus, is highly similar to human ACE2 and this may contribute to the high susceptibility of felids to SARS-CoV-2 infection (3).
Despite current evidence showing most cases of SARS-CoV-2 in felids are spillover infections resulting from close contact with infected humans (11), SARS-CoV-2-specific antibodies have been found in stray cats in Rio De Janeiro (12), and in abandoned cats in Wuhan, indicating cats might be infected from other sources (13). Similarly, cat-to-cat transmission has been demonstrated experimentally (14, 15, 16).
Given that domestic cats are frequently in close contact with humans, if they become a reservoir for the virus, they could initiate new outbreaks or re-introduce SARS-CoV-2 into humans (18). Moreover, if SARS-CoV-2 adapts to replicate more efficiently in cats, they could contribute to the emergence of novel variants.
It has been suggested that the Omicron variant might have emerged from a cross-species transmission of SARS-CoV-2 into an animal reservoir, in which mutations accumulated, then spilled back to humans (19). This pattern of variant emergence was observed during the 2020 outbreak of SARS-CoV-2 on Dutch mink farms (20). Infection of stray cats living on a mink farm, suggestive of mink-to-cat transmission, has also been reported (21, 22).
Several clinical outcomes of feline SARS-CoV-2 infection have been documented (23), from asymptomatic infections (24) to mild respiratory signs (25). More severe sequelae include myocarditis (26, 27), which can be severe and lead to death or necessitate euthanasia.
Estimating the frequency of asymptomatic infections by RT-qPCR is technically challenging as there is a narrow window of positivity (28). Cui et al (2020) suggested cats might be less likely to display signs than humans as two key sensory components of the inflammasome pathway, Aim2 and NLRP1, are absent in both domestic cats and tigers (29).
It was hypothesized that this might confer an evolutionary advantage of a reduction in excessive cytokine release, resulting in less host tissue damage and milder inflammatory symptoms during SARS-CoV-2 infection in these animals.
Despite the potential impact of SARS-CoV-2 on feline health, there is currently no official surveillance program for monitoring SARS-CoV-2 infection or exposure in UK cats. Diagnostic RT-qPCR testing has primarily been undertaken by researchers and has been constrained by a narrow case definition by the UK’s competent authority(30).
It has been demonstrated experimentally that domestic cats mount a neutralizing antibody response against SARS-CoV-2 that prevents re-infection from a second viral challenge (16) and a feline IgG response has been detected against both the nucleocapsid and spike proteins via ELISA (31, 32).
Cats have also been found to produce a neutralizing antibody response against multiple SARS-CoV-2 variants (33).
The antibody response to both SARS-CoV-2 infection and vaccination in humans wanes over time, more rapidly than for other human coronavirus infections, allowing for re-infection with SARS- CoV-2 (34, 35).
It has also been found that less severe clinical outcomes (36) and longer-lived immunity is exhibited by children than adults in response to SARS-CoV-2 infection (37). However, it is unknown if feline SARS-CoV-2 immunity is transient or if age-dependent immune longevity and clinical outcomes are also a feature of feline infections.
In humans, virus neutralizing antibodies generated in response to SARS-CoV-2 vaccines, currently based on the ancestral Wuhan-Hu-1 strain, are less effective against the Delta and Omicron variants (38, 39, 40, 41, 42). A cat that has been infected with one variant might resist re-infection with the same variant but remain susceptible to infection with a different variant, similar to the phenomenon observed in humans (43).
There are many breeds of domesticated cat, and it is possible genetic differences generated by selective breeding could have an impact on immunity (44), susceptibility to infection or the severity of clinical signs, whether by selection for a genetic defect or narrowing of major histocompatibility complex (MHC) diversity.
For example, pedigree cats are more likely to develop feline infectious peritonitis following feline coronavirus infection than non-pedigree cats (45).
However, it should be appreciated that the breeding of pedigree cats is often associated with other risk factors such as multi-cat households and being kept indoors, and the actual genetic basis for susceptibility has not been quantified.
The aim of the present study was to assess the seroprevalence of SARS-CoV-2 infection in UK cats during the COVID-19 pandemic, using an ELISA to measure antibodies recognizing the receptor binding domain of the SARS-CoV-2 S-protein and a pseudotype-based neutralization assay to measure titers of virus neutralizing antibodies.
Neutralizing titers were measured against a panel of HIV (SARS-CoV-2) pseudotypes bearing the S protein of the predominant circulating variants in the UK to investigate the specificity of the neutralizing response and whether it correlated with the variants likely to have been circulating at the time of infection.