Introduction
- Dileepan M
- Di D
- Huang Q
- et al.
,
- Račnik J
- Kočevar A
- Slavec B
- et al.
,
- Sit THC
- Brackman CJ
- Ip SM
- et al.
zoo (feline species
- McAloose D
- Laverack M
- Wang L
- et al.
and gorillas), farmed (mink),
- Oude Munnink BB
- Sikkema RS
- Nieuwenhuijse DF
- et al.
and wild (white-tailed deer)
- Hale VL
- Dennis PM
- McBride DS
- et al.
animals. Experimental challenge has identified that non-human primates, hamsters, ferrets, American minks, cats, dogs, raccoon dogs, North American deer mice, Egyptian fruit bats, Asian small clawed otters, and white-tailed deer were highly susceptible to SARS-CoV-2 infection.
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Infection with SARS-CoV-2 in animals.
Animal-to-animal transmission has been observed in hamsters,
- Sia SF
- Yan LM
- Chin AWH
- et al.
ferrets,
- Kim YI
- Kim SG
- Kim SM
- et al.
cats,
- Shi J
- Wen Z
- Zhong G
- et al.
mink,
- Oude Munnink BB
- Sikkema RS
- Nieuwenhuijse DF
- et al.
raccoon dogs,
- Freuling CM
- Breithaupt A
- Müller T
- et al.
fruit bats,
- Schlottau K
- Rissmann M
- Graaf A
- et al.
deer mice,
- Fagre A
- Lewis J
- Eckley M
- et al.
and white-tailed deer.
- Hale VL
- Dennis PM
- McBride DS
- et al.
Sustained transmission and continuous evolution of SARS-CoV-2 in animals have been documented in large mink farm outbreaks
- Oude Munnink BB
- Sikkema RS
- Nieuwenhuijse DF
- et al.
,
- Hammer AS
- Quaade ML
- Rasmussen TB
- et al.
and in white-tailed deer populations.
- Hale VL
- Dennis PM
- McBride DS
- et al.
So far, zoonotic transmission has only been shown for the mink-adapted SARS-CoV-2 variant during mink farm outbreaks in countries where large numbers of infected animals were housed in high density.
- Oude Munnink BB
- Sikkema RS
- Nieuwenhuijse DF
- et al.
,
- Hammer AS
- Quaade ML
- Rasmussen TB
- et al.
- Sia SF
- Yan LM
- Chin AWH
- et al.
Despite their high susceptibility to SARS-CoV-2, hamsters have not yet been reported to be infected outside of experimental settings.
Evidence before this study
We searched PubMed on Jan 24, 2022, with no starting date limitations, using the terms “SARS-CoV-2” and “zoonotic transmission” for articles in English. Transmission of SARS-CoV-2 from humans to different mammalian species, including pet animals, has been reported. However, the only example of such viruses being transmitted back to humans has been from farmed mink. Hamsters can be experimentally infected with SARS-CoV-2 and the virus can transmit between hamsters in experimental settings.
Added value of this study
This study reveals that pet hamsters can naturally acquire SARS-CoV-2 infection and can transmit the virus back to humans. SARS-CoV-2 circulating in hamsters can lead to sustainable virus transmission in humans. Our work highlights that some pet animals can be an additional reservoir of SARS-CoV-2. This study also suggests that the pet animal trade might be a pathway that can facilitate the movement of SARS-CoV-2 across national borders.
Implications of all the available evidence
This study expands our understanding of the animal reservoirs of SARS-CoV-2 in nature. Awareness and appropriate quarantine and control policies are needed to reduce these reverse zoonotic (human to animal) and zoonotic (animal to human) events.
- Gu H
- Chu DKW
- Chang LDJ
- et al.
with no known local circulation of SARS-CoV-2 between Oct 9 and Dec 31, 2021. On Dec 24, 2021, the omicron variant was introduced via returning air crew, which led to multiple chains of local transmission. There were no known locally acquired infections with the delta variant since Oct 9, 2021. In this Article, we report an outbreak of SARS-CoV-2 delta variant first identified in a pet shop worker on Jan 15, 2022. Subsequent investigation identified imported pet hamsters as the viral source. Such virus introduction led to more than one hamster-to-human zoonotic transmission event, resulting in onward human-to-human transmission in Hong Kong.
Results
Table 1Chronology of outbreak investigation
RT-qPCR=quantitative RT-PCR.
FigurePhylogenetic of SARS-CoV-2 delta variant AY.127 virus sequences detected in humans and hamsters
Viral genomes (case number and detection date) detected from the studied local AY.127 human (red) and hamster (green) cases. Representative AY.127 genomes from imported cases in Hong Kong (blue; internal case number and detection date) and overseas cases, and representative genomes from other pangolin lineages are included in the analysis. Only values for highly supported branches (first value is the Shimodaira-Hasegawa approximate likelihood ratio ≥80% and second value is ultrafast bootstrap ≥95%) are shown. Scale bar indicates estimated genetic distance. HK=Hong Kong.
Table 2SARS-CoV-2 RT-qPCR confirmed samples collected in the studied sites
Number of tested samples (number of samples positive for SARS-CoV-2). RT-qPCR=quantitative RT-PCR.
- Horiuchi S
- Oishi K
- Carrau L
- et al.
the detection of two animals with viral RNA but without antibodies suggests that infection might be a recent event.
Table 3Detection of SARS-CoV-2 exposed or infected hamsters at the pet shop or at the warehouse
Data are n or n (%). sVNT=surrogate virus neutralisation test.
Hamster swabs positive for SARS-CoV-2 by RT-qPCR with high viral load (cycle threshold values of <30) were cultured for virus isolation and two virus isolates were obtained, one from the warehouse and one from pet shop A.
The hamsters at the affected warehouse were imported from the Netherlands to Hong Kong in two different batches (arrival dates Dec 22, 2021, and Jan 7, 2022). The consignment that arrived on Dec 22, 2021, was transported by Qatar Airways and transited in Doha, Qatar, involving change of aircraft; the transit time was around 15 h. Water was topped up, but no food was provided to the animals. This consignment had 96 rabbits, 990 Phodopus sungorus (white dwarf hamster), and 90 Phodopus roborovskii (Roborovski dwarf hamster). The consignment that arrived on Jan 7, 2022, was transported by KLM, which stopped over in Bangkok, Thailand, but without change of aircraft. The cargo hold was opened for off-loading the cargo designated for Bangkok, but the animals did not leave the aircraft. No additional water or food was provided. The transport cages had a mesh covering, so contamination during transit cannot be excluded. This consignment had 116 rabbits, 720 white dwarf hamsters, 118 Syrian hamsters, 25 guinea pigs, and 30 chinchillas. The hamsters were initially kept in the warehouse on arrival and smaller consignments delivered to the retail shops, meaning that the warehouse did not operate on an all-in all-out basis. Some hamsters arriving on Jan 7, 2022, were transferred to pet shop A on the day of arrival.
At the time of preparing this Article, additional human cases with an epidemiological link to hamsters or hamster-related human cases were detected. As of Feb 3, 2022, there were 82 patients in this hamster-related cluster, all of whom were confirmed positive for SARS-CoV-2 infection by RT-qPCR and tested positive for the Leu452Arg mutation in the spike protein (delta).
- McCallum M
- De Marco A
- Lempp FA
- et al.
and the His49Tyr mutation can enhance viral entry.
- Ozono S
- Zhang Y
- Ode H
- et al.
Asp427Gly is not located in the receptor binding motif that direct interacts with host ACE2,
and its impact on ACE2 receptor binding and other biological functions require further investigation. These three spike mutations can be found in other sequences submitted to GISAID at various frequencies (Leu18Phe 3·31%; His49Tyr 0·17%, and Asp427Gly 0·01%). Whether these three mutations found in the hamster viruses were pre-existing or adaptive mutations requires further investigation.
Table 4Non-silent mutations found in AY.127 genes from infected humans and hamsters.
Discussion
Our findings provide evidence of maintenance of SARS-CoV-2 delta variant (AY.127) by hamster-to-hamster transmission between pet Syrian hamsters, hamster-to-human zoonotic transmission, and further onward spread between humans.
Specifically, we found that Syrian hamsters at a warehouse and two pet shops (A and C) supplied by the same warehouse had evidence of SARS-CoV-2 infection. The viruses in hamsters in these premises were genetically highly similar and they form a unique clade in the phylogenetic tree. However, these viruses were not genetically identical, suggesting that transmission in these hamsters had been ongoing for some time. The evolutionary rate of SARS-CoV-2 in hamsters might differ from that in humans and requires further investigation. Nonetheless, the SARS-CoV-2 infecting patient 1 who worked in pet shop A was highly similar to these hamster viruses, with only one nucleotide difference to viruses in some hamsters. Viral genetic analysis suggests that patient 2 independently acquired infection from other hamsters in pet shop A and did not acquire infection from patient 1. Thus, our findings suggest that there were independent hamster-to-human zoonotic transmission events in this study. Given that viruses in hamsters was similar to the virus sequenced from the warehouse, and because both patients 1 and 2 did not visit either the warehouse or pet shop C, the findings are highly suggestive that infection in Syrian hamsters in the warehouse was the source of infection in pet shops A and C and also of patients 1 and 2. Taken together, the most likely conclusion is that both patient 1 and patient 2 acquired infection directly from infected hamsters in pet shop A. Patients 2 and 4 visited pet shop A on Jan 4, 2022, and again on Jan 8, 2022. The hamster purchased by these two patients on Jan 4, 2022, was negative for SARS-CoV-2 by RT-qPCR. Because patient 2 developed symptoms on Jan 12, 2022, and given the mean incubation period of SARS-CoV-2 is around 5 days, it would be probable that she acquired infection from infected hamsters during her visit to the pet shop on Jan 8, 2022, rather than the previously purchased hamster. The alternative hypothesis that the index case (patient 1) got infected from an undetected human chain of delta virus transmission within Hong Kong and then transmitted infection to hamsters in pet shop A, pet shop C, and the warehouse is implausible, given the genetic diversity in the virus found in hamsters in the pet shop.
- O’Toole Á
- Scher E
- Rambaut A
There were two shipments arriving at the warehouse, but the shipment on Dec 22, 2021, had only dwarf hamsters and the shipment on Jan 7, 2022, had only Syrian hamsters. Thus, the Jan 7, 2022 shipment was a probable source of SARS-CoV-2 delta AY.127 introduction. It was established that hamsters arriving on this shipment to the warehouse were supplied the same day to pet shop A. This further corroborated the animal-to-human transmission risk at pet shop A.
This study has some limitations. Not all the hamsters in the concerned pet shops and warehouse were studied. Imported hamsters sold before this investigation cannot be tested. Information about the pet trading practices and these animal facilities is scarce. Thus, this study might underappreciate the virus diversity found in the affected hamster population. Although unlikely, the possibility of an undetected local chain of transmission of SARS-CoV-2 delta AY.127 leading to infection of hamsters in the warehouse cannot be excluded.
- Oude Munnink BB
- Sikkema RS
- Nieuwenhuijse DF
- et al.
,
- Hammer AS
- Quaade ML
- Rasmussen TB
- et al.
Pet dogs and cats have been reported to acquire SARS-CoV-2 infection from infected humans within the household but there is no evidence of transmission of virus back to humans.
- Sit THC
- Brackman CJ
- Ip SM
- et al.
,
- Barrs VR
- Peiris M
- Tam KWS
- et al.
This case report is evidence of zoonotic transmission of SARS-CoV-2 from pets to humans and also of pet hamsters being infected naturally. Most importantly, the SARS-CoV-2 that circulated in hamsters, which is still genetically highly similar to human SARS-CoV-2, can lead to human-to-human transmission. This incident demonstrates that SARS-CoV-2 can be transferred across international borders via the pet animal trade. There are other examples of viruses being moved across international borders via the pet trade, such as an outbreak of monkey pox in the USA attributed to importation of exotic animals from Africa.
- Reed KD
- Melski JW
- Graham MB
- et al.
Multiple reports, including this one, have suggested the ease with which SARS-CoV-2 can spill-back from humans to pets (eg, dogs, cats, hamsters), farmed animals (eg, mink), and wildlife (eg, white-tailed deer). Although many of these spillovers do not result in maintenance of the virus in the animal species, it has been shown to occur in mink, white-tailed deer, and hamsters. Because surveillance at the animal–human interface is so sparse, it is probable that these examples are part of a wider problem. Such events provide opportunity for the virus to evolve in unsuspected and in unpredictable ways, with possibility of future zoonotic transmission events leading to novel variants in the human population. There might also be unpredictable adverse outcomes in wildlife. Our findings, together with those from others, highlight the need of systematic surveillance of SARS-CoV-2 in both wild and domesticated animals. Mammals known to transmit SARS-CoV-2 should also be monitored on a regular basis. For human COVID-19 cases with atypical SARS-CoV-2 sequence features, additional testing on animals in affected sites and investigation into their animal contact history should be considered. The present study has also highlighted the possibility of viruses being moved across international boundaries via the pet trade.
In summary, we provide evidence of pet hamsters naturally acquiring SARS-CoV-2 delta variant and being the source of human infection. We also provide evidence suggesting the possibility of international movement of SARS-CoV-2 via the pet trade. The relatively low level of SARS-CoV-2 transmission in Hong Kong at the beginning of this outbreak and the application of the One Health approach in this investigation probably allowed the detection and investigation of this zoonotic incidence. Similar events might be occurring, unsuspected, in many other parts of the world. These findings highlight that SARS-CoV-2 may be spilling over to other animal species unsuspected and providing an additional reservoir for the virus for further adaptation and zoonotic spillover back to humans. The findings highlight the need for awareness, surveillance, and for appropriate quarantine and control policies for the pet animal trade. Additional control measures that prevent reverse zoonosis of SARS-CoV-2 from humans to animals might help to reduce these undesirable animal-to-human transmission events.
Samuel M S Cheng, Lydia D J Chang, Pavithra Krishnan, Daisy Y M Ng, Gigi Y Z Liu, Mani M Y Hui, Sin Ying Ho, Wen Su, Sin Fun Sia, Ka-Tim Choy, Sammi S Y Cheuk, Sylvia P N Lau, Amy W Y Tang, Joe C T Koo, Louise Yung (all members are from the School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China).
THCS, H-LY, GML, MP, and LLMP conceptualised the study and provided supervision. SSYC (Government Agriculture, Fisheries and Conservation Department [AFCD]), KWST, WS, SFS, and K-TC facilitated or conducted field investigations; CJB, PYTL, SMSC, and HG curated the data; SSYC (The University of Hong Kong), LDJC, DYMN, PK, GYZL, MMYH, SYH, SPNL, AWYT, JCTK, and LY did the laboratory work; H-LY, GML, MP, and LLMP acquired funding; H-LY, GML, MP, and LLMP wrote, reviewed, and edited the manuscript. All authors critically reviewed and approved the final version. All authors confirm that they had full access to all the data in the study and accept responsibility to submit for publication.