key: cord-0871106-kro7y310 authors: Rabalski, Lukasz; Kosinski, Maciej; Mazur-Panasiuk, Natalia; Szewczyk, Boguslaw; Bienkowska-Szewczyk, Krystyna; Kant, Ravi; Sironen, Tarja; Pyrc, Krzysztof; Grzybek, Maciej title: Zoonotic spillover of SARS-CoV-2: mink-adapted virus in humans date: 2021-12-15 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2021.12.001 sha: b8989dab2b0189ca4f5725385b77f118dbf2db1f doc_id: 871106 cord_uid: kro7y310 OBJECTIVES: This work aimed to analyse possible zoonotic spillover of SARS-CoV-2. We report the spillover of mink-adapted SARS-CoV-2 from farmed mink to humans after adaptation that lasted at least three months. METHODS: Next –Generation Sequencing and bioinformatic approach were applied to analyse the data. RESULTS: In an isolate obtained from an asymptomatic patient testing positive for SARS-CoV-2, we found four distinguishing mutations in the S gene that gave rise to the mink-adapted variant (G75V, M177T, Y453F, and C1247F) and others. CONCLUSIONS: Zoonotic spillover of SARS-CoV-2 can occur from mink to human. Coronaviruses are potential zoonotic pathogens, and severe acute respiratory syndrome 28 (SARS) coronavirus 2 (SARS-CoV-2) is the third highly pathogenic member of this 29 family to emerge in the 21 st century (1). Although mass vaccinations are currently 30 underway, the fate of the virus remains unclear. Herd immunity and eradication are 31 somewhat unrealistic given its prevalence, genetic diversity, and existing animal 32 reservoirs. Thus far, SARS-CoV-2 infections have been reported in different 33 mammalian species worldwide, including dogs, domestic cats, tigers, lions, ferrets, 34 minks, deer and maintained in rodents (2-5). SARS-CoV-2 infections in farmed mink 35 have recently been confirmed in Europe (6), and transmission of the virus from infected 36 mink to humans has been reported in Denmark and the Netherlands (7-9). After 37 Denmark, Poland species remain puzzling, but one obvious possibility is that, as with SARS-CoV-2, these 49 viruses spread between humans and companion and farmed animals (13). Recently, we and others have detected SARS-CoV-2 infection in farmed minks in Northern Poland 51 (14,15). The first report identified SARS-CoV-2 in samples collected from minks in 52 mid-November 2020. Even though the prevalence of the virus was low and cases most 53 likely were isolated, we have sequenced the isolates and shown that the positive signal 54 did not originate from contamination. The aim of this study was to detect possible 55 zoonotic spillover of SARS-CoV-2 from minks to farm workers. We report a SARS-CoV-2 zoonotic spillover from farmed mink to a farm worker. In an 114 isolate obtained from an asymptomatic farm employee testing positive for SARS-CoV-115 2, we found four distinguishing mutations in the S gene that gave rise to the mink-116 adapted variant (G75V, M177T, Y453F, and C1247F) and others. These new changes 117 include the Y453F mutation, which was previously reported to have emerged in minks 118 during serial passages (e.g., in Denmark and recently Lithuania) (17), and a novel 119 mutation that is not present in any global SARS-CoV-2 isolate, which truncates ORF 7b 120 at position L22. Considering all of the data, we speculate that the virus already was 121 present in the mink population in November 2020, presumably after a single 122 introduction during the late summer or fall season. 1218 nsp2: S138L C T T T 1630 nsp2: Q275H A T T T 2426 nsp2: V541I G A A A 3373 nsp3: D218E C A A A 5326 nsp3: E869D G T T T 12795 nsp9: G37E G G A G 12854 nsp9: P57S C C T C 14408 nsp12: P323L C T T T 18186 nsp14: M49I G T T G 18859 nsp14: A274S G T T T 20273 nsp15: M218T T C C C 21786 S: G75V G T T T 22092 S: M177T T T C T 22920 S: Y453F A A T A 25302 S: C1247F G T T G 27820 ORF 7b: L22* T T A T 28881/2 N: R203K GG AA AA AA 28884 N: G204L G T T G 29300 N: D343Y G T T WHO Declares COVID-19 a Pandemic Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2. 178 bioRxiv Evidence for SARS-CoV-2 Infection of 180 CoV-2 infection and transmission in the North American deer mouse Assessing the SARS-CoV-2 threat 186 to wildlife: Potential risk to a broad range of mammals World Organisation for Animal Health. World Organisation for Animal Health Transmission of SARS-CoV-2 on mink farms between 197 humans and mink and back to humans Fur Association. EU Fur Association. 2020 SARS and MERS: recent 200 insights into emerging coronaviruses History and Recent Advances in Coronavirus Discovery Canine Respiratory Coronavirus, Bovine Coronavirus, and Human Coronavirus 205 OC43: Receptors and Attachment Factors Acute Respiratory Syndrome Coronavirus 2 in Farmed Mink Nextstrain: real-time tracking of pathogen evolution The SARS-CoV-2 Y453F mink variant displays a pronounced 216 increase in ACE-2 affinity but does not challenge antibody neutralization The Potential Intermediate Hosts for SARS-CoV-2. Front 219 19 Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid 222 host-adaptation Effect of RBD mutation (Y453F) in spike 224 glycoprotein of SARS-CoV-2 on neutralizing antibody affinity J o u r n a l P r e -p r o o f G T T T 12795 nsp9: G37E G G A G 12854 nsp9: P57S C C T C 14408 nsp12: P323L C T T T 18186 nsp14: M49I G T T G 18859 nsp14: A274S G T T T 20273 nsp15: M218T T C C C 21786 S: G75V G T T T 22092 S: M177T T T C T 22920 S: Y453F A A T A 25302 S: C1247F G T T G 27820 ORF 7b: L22* T T A T 28881/2 N: R203K GG AA AA AA 28884 N: G204L G T T G 29300 N: D343Y G T T G