Since December 2019, a new virus denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened the entire world. This virus, the causative agent of the disease named COVID-19, is an enveloped single-stranded RNA virus belonging to the Coronaviridae family, Beta genus (1). The viral genome includes 13 open reading frames (ORFs) and four major structural proteins: the surface Spike (S) protein, the envelope (E) protein, the matrix protein (M), and the nucleocapsid (N) protein (2). Following the global spread of SARS-CoV-2, the emergence of new variants of the virus has kept the world on tenterhooks. Among the numerous variants, some of them have been proved to be even more hazardous than the original strain. These variants, denominated as variants of concern (VOCs), present higher transmission rates and a more effective evasion of the host immune system, which makes it more difficult the adequated control of the disease. The first determined VOC was the B.1.1.7 (20I/N501Y.V1), which was identified in England (3). After this event, a second variant with the N501Y mutation was first detected in South Africa, named B.1.351 (20J/N501Y.V2) (4), and lately, the P.1 variant was reported in Brazil (20I/N501Y.V3) (5). Despite their hazardous properties, vaccination implementation helped to control the damages caused by these variants. However, since late March 2021, India started experiencing an increase in the number of COVID-19 cases reaching more than 400,000 cases and 4,000 deaths reported each day in early May 2021 (6). These fatalities were associated with a new lineage, the B.1.617.2 (Delta) variant, that was first detected in India in December 2020 and became the most commonly reported variant in the country by mid-April 2021. The delta variant is characterized by the spike protein mutations T19R, Δ157-158, L452R, T478K, D614G, P681R, and D950N. Several of these mutations may alter host immune response and increase viral replication, leading to higher viral loads and increased transmission rates (7). Currently, the Delta variant has been replaced by a new heavily mutated variant known as B.1.1.529 (BA) (Omicron) (8), first reported in South Africa on November 24, 2021 (9). This new variant has dominated the current epidemiologic scenario, replacing the present Delta prevalence around 4.2% in Spain (10).

Although the concern regarding the delta variant in the human population is widely documented, little is known about the transmission capacity and the effects of this variant in animals. Due to the zoonotic origin of the COVID-19 disease, numerous experimental and field studies have been conducted in order to explore the extent of the infection in animals and to elucidate their role as reservoirs (11–15). Concretely, efficient SARS-CoV-2 transmission between owners and their pets has been demonstrated worldwide (16–18). Among the different animals affected, cats have been shown to be one of the more susceptible species (19). One proof of this is the high number of SARS-CoV-2 sequences retrieved from cats submitted to the GISAID website, which corresponds with 119 sequences from different parts of the world. In addition, several studies have reported natural infection with SARS-CoV-2 in this species (15, 17, 18). We cannot dismiss, therefore, the potential role of cats as intermediate hosts of the virus, which may trigger the development of new mutations in the viral genome. Moreover, genomic surveillance in infected pets has evidenced animal infection with at least one VOC, the B.1.1.7 alpha variant (20–22). These events highlight the importance of performing genetic investigations on samples from infected cats in order to understand the transmission and evolution of the virus in these hosts.

To the best of our knowledge, here, we documented the first human to domestic cat transmission of the SARS-CoV-2 B.1.617.2 (delta) variant in Spain. Although the cat only presented subtle clinical signs, it showed high levels of viral RNA in the oropharyngeal swab taken. These facts suggest an active viral infection and open the question of whether the cat would act as a source of virus.

This is, to our knowledge, the first report of the B.1.617.2 (Delta) VOC in a cat pet worldwide, which confirms the transmission of this variant can occur between infected people and their pets, at least in the case of cats. This variant, which is currently the most prevalent SARS-CoV-2 strain has shown higher transmission rates even in vaccinated people causing a decrease in vaccine effectiveness (30, 31). For these reasons, recent vaccine effectiveness studies now focus on this variant (32, 33). All these facts evidence the importance of exploring the reach of this variant in all the possible scenarios, and, therefore, to know if this VOC can infect pets which may act as a potential source of infection. In addition, the emergence of new variants associated with animal infections cannot be dismissed, as has previously occurred in the case of minks (34, 35).

In this study, we investigated a reverse zoonosis event in a pet cat living with a COVID-19 positive owner. The cat presented light symptoms of the disease (sneezing) and was sampled during the quarantine period of its owner. Molecular analysis was performed in several samples from the cat and SARS-CoV-2 infection was confirmed by RT-qPCR, following a genomic investigation from the positive sample (oropharyngeal swab). Thus, the phylogenetic assay revealed that the sequence from the cat presented the mutations proper of the B.1.617.2 (delta) VOC. It is also noteworthy that transmission between the infected human and the cat occurred despite the owner having a complete vaccination schedule. This finding alerts us about the high transmission capacity of this VOC, which avoided all the boundaries and jumped from the owner to the pet. The animal also developed neutralizing antibodies, which demonstrates that an active infection occurred following an effective immune system response.

Although numerous human-based studies have demonstrated the dramatic consequences associated with infection by this VOC in humans (36, 37), little is known about its impact on animal infection. Several field studies have previously demonstrated the presence of infection with the B.1.1.7 VOC in pets (20–22), observing associated symptoms such as cardiomyopathies in some of these cases (21).

The delta variant has been reported to be even more transmissible than other VOCs previously detected, such as the B.1.1.7 variant (33, 38). In addition, vaccine effectiveness seems to be decreased in the case of infection with this variant, as some reports have evidence (32, 38). This fact may explain that the owner of the infected cat reported in this study was able to transmit the virus to the pet, despite being completely vaccinated. Although the virus was not isolated from the cat sample, a high viral load was detected in the animal's oropharyngeal swab, that allude to an active infection at the time of sampling. In addition, the cat had compatible symptoms with the disease, without any known comorbidities. Taking into account that experimental studies have reflected that cats often do not present clinical signs when become infected (39), the presence of sneezing in this cat, may suggest a higher virulence of the isolate. Under this scenario, the role of the cat as an active source of infection cannot be dismissed, as well as the potential capacity of the virus to mutate into the animal. All these facts together highlight the risk associated with pet delta variant infection and underline the importance of performing active surveillance in pets living with COVID-19 infected people, including genomic investigation in order to detect infections with VOCs or potential mutations associated with animal hosts.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://www.ncbi.nlm.nih.gov/genbank/, OL336792.

The animal study was reviewed and approved by Complutense University of Madrid's Ethics Committee for Animal Experiments (Project License 14/2020). Written informed consent was obtained from the owners for the participation of their animals in this study.

SB-A and LS-M performed the sampling, veterinary inspection, and laboratory analysis and wrote the initial manuscript. LD and JS-V acquired the funds. MP-S, LD, and JS-V reviewed the manuscript. All authors have read and approved the final version of the manuscript.

The Institute of Health Carlos III (ISCIII) was the project Estudio del potencial impacto del COVID19 en mascotas y linces founder (reference: COV20/01385).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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