A Dreadful Loop: Can Reverse Zoonosis of COVID-19 Seed Unrestrained Spread and Mutations in Wild Species and Transmission of Novel Strains to Humans?

Abstract

The disucssion deals with a hypothetical but an emerging scenario: reverse zoonosis and consequences. The infection of SARS-CoV-2 is effectuated by interactions between the SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 (ACE2) receptor proteins. An immense diversity of mammals can be infected by SARS-CoV-2 via their ACE2 proteins, which has been proven on some 30 species. In a pandemic with numerous locations of community-wide spread of the zoonotic agent, human-animal contacts or anthropogenic wastes carrying SARS-CoV-2 allows reverse zoonosis, namely the transmission of the virus from infected persons to wildlife species. Reverse zoonosis of SARS-CoV-2 may seed unrestrained spread and mutations in wildlife and, at some stage, transmission of novel strains back to humans (“reverse anthroponosis”). With no human intervention, spontaneous behaviors of wildlife such as foraging, predation, mating, and defecating enable both in-species and cross-species transmission, facilitating genotype changes and evolution of SARS-CoV-2 in various wildlife reservoirs. Multiple studies showed the complex evolutionary origin of SARS-CoV-2, which is susceptible to further mutations with its transmission between different hosts and species. As of week 21, 2020, a total of 11,627 genomes (34%) of SARS-CoV-2 isolated from humans showed single mutations, and there have been at least six published cases of SARS-CoV-2 reinfections around the globe since the first case appeared in Hong Kong on Aug 24, 2020. In all six cases, viral strains isolated from reinfected individuals showed substantial genetic differences from those causing their first infection. Although there has been no report on mutated SARS-CoV-2 strains from infected animals, COVID-19 is an evolving situation and recent accounts of clustered infections in farmed minks and reports of human-to-animal transmission in a New York zoo and in a Dutch mink farm highlighted these risks. Should reverse zoonosis occur on a considerable scale, mutated viruses may then spillover to humans again through different natural or intermediate hosts, forming a dangerous loop of zoonosis, anthroponosis, and reverse anthroponosis of the evolving virus between humans and other hosts. Once transmitted to humans, those novels strains will pose new challenges for future infection control by causing reinfections, re-emergent outbreaks, and rendering current vaccines less effective. In this article, we present this hypothesis based on emerging evidence on two-way spillover of SARS-CoV-2 between humans and animals, and call for early intervention with strategies proposed to prevent the risks down the road.