key: cord-0982337-k9lcpjyo
authors: Goumenou, Marina; Spandidos, Demetrios A.; Tsatsakis, Aristidis
title: Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy
date: 2020-03-23
journal: Mol Med Rep
DOI: 10.3892/mmr.2020.11037
sha: edd969fc25d588a13278f550d06749713f72aa90
doc_id: 982337
cord_uid: k9lcpjyo

Covid‑19 origin and transmission to humans. Covid‑19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid‑19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS‑CoV‑2 transmission. However, the source(s) and transmission routine(s) of SARS‑CoV‑2 remain elusive' (1).

covid-19 infection began in Wuhan (Hubei, china) in december, 2019. although to date it is considered that covid-19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2) (3) (4) . Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS-CoV-2 transmission. However, the source(s) and transmission routine(s) of SARS-CoV-2 remain elusive' (1) .

In Italy, the first two cases were entered on January, 23 and were identified in January 29, 2020. Until February 24 the positive cases identified were 221. Despite the fact that a number of restrictive measures have been taken for preventing the gathering of individuals, or even preventing their circulation out of the house, at almost 1 month from that time (March 20, 2020), the number of positive cases increased to 37,860 (with 4,035 deaths, more than those occurring in china) and a plateau in the respective curve has not yet been reached (5) (Fig. 1) .

SarS-coV-2 is a β-coronavirus similar to SarS-coV (79.5% shared identity) (4) . Viral infection begins with an initial attachment step, namely the binding of the virus to the respective host cell receptor. SarS-coV has been studied since the outbreak in 2002. it is well known that the virus enters cells through the binding of its spike protein receptor-binding domain (rBd) to the angiotensin-converting enzyme 2 receptor (ace2). although the 2019-ncoV rBd has not yet been fully investigated, it shares same common characteristics with SarS-coV and it has the ability to bind to human ace2 (6) . ace2 receptors exist in a number of animals and this is the reason why inter-species contamination is possible. The efficiency of this binding depends on the affinity between the RBD of the virus and the species-specific ACE2. Although it is already known that rats and mice are not susceptible, the issue of covid-19 rBd recognition of ace2 of dogs remains unresolved.

To our knowledge, the only available information for covid-19 in dogs is derived from Hong Kong. On February 27, a Pomeranian was tested as weak positive for covid-19 from the Agriculture, Fisheries and Conservation Department of Hong Kong (7) . it is believed that dog's infection was possibly due to transmission from his infected owner (a human-to-animal transmission). The dog remained under quarantine and samples taken on February 28 and on March 2, were again weak positive, confirming the case of infection (instead of just mouth and nose contamination from the household). The dog was asymptomatic during the whole period of infection. The AFCD of Hong Kong stated: 'Although there is no evidence yet that pets can transmit the virus to other pets or back to humans, we strongly advise that mammalian pets including dogs and cats from households with persons confirmed as infected with COVID-19 or as close contacts of COVID-19 infected persons should be put under quarantine in AFCD facilities to safeguard public and animal health. We will review this arrangement from time to time taking into account new information that becomes available' (7) .

The right now. It should be discussed, however, if we start seeing more cases like the Hong Kong Pomeranian'. responding in the question if pets can serve as a reservoir of the virus and pass it back to us she responded that 'If pets can become infected -and we don't know if they can -then yes, they could serve as a reservoir. And in that case, we'd need to deal with them the same way we're dealing with human cases. We'd need to figure how to treat them. Like human hospitals, vet hospitals would have to be prepared for a surge in the number of cases' (11) .

it is known that SarS-coV can infect domestic cats and lead to transmission between them, although without manifestation of symptoms (12) . although data for SarS infection to dogs could not be found, there are data available to support that dog ace2 has a 87% nucleotide identity and 81% amino acid identity with human ace2, and also functions as a SarS-coV receptor (13). in addition, it is generally known that various cell lines without ace2 are still permissive for SarS-coV, indicating the existence of more receptors. no data regarding this case in dogs are available.

italy is the second country in europe (after Hungary) in which the possession of a pet is common, with >50% of homes owning one (14) . owning a dog as a pet in italy is extremely common. The available information refers to a total of c.a. 10.000.000 registered dogs (by tattoo or microchip), indicating c.a. 1 dog for every 6 individuals. as regards their distribution, 1.392.197 and 1.079.884, 1.172.344 of these cases are in lombardia, emilia romagna and Veneto, respectively (15) .

To summarise, it is known that: i) Globally, to date, only 4 dogs have been tested for covid-19. These dogs had come into contact with infected individuals; ii) dogs have an ace2 that functions as a SarS-coV receptor; iii) dog ace2 is similar to human ace2; iv) the infection of animals from humans and vice versa is plausible; v) no data are available to confirm or exclude the possibility of such human-to-dog and dog-to-human infection; and vi) precautionary measures for such cases have been proposed from all authorities; however, it is highly questionable whether these are followed by dogs owners.

although >2 weeks have already passed from the time when italian authorities restricted citizen mobility, the exponential increase in the number of positive cases and deaths continues. To date, there is no satisfactory explanation for this phenomenon. exception from the mobility restriction in all territories, is the mobility for taking out dogs. in a number of cases, this exception is over-used. Therefore, further than the every-day contact between dogs and italian families, there is a constant more-than-one, every-day contact between animals and other owners.

all the above facts create the need to reconsider the possibility that dogs are intermediate hosts contributing to the extremely high covid-19 transmission in north italy. Possible actions to this direction could include the biased testing of dogs living in houses with positive cases opposed to home quarantine, and non-experimental studies for the investigation of such transmission, using appropriate methodologies such as in silico docking to evaluate the binding of covid-19 with dogs ace2 (16) and sequence-based computational estimations of hosts susceptibility (17) .

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