Phodopus Roborovskii Research Articles

Neural network-assisted humanisation of COVID-19 hamster transcriptomic data reveals matching severity states in human disease

Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Integration of data from patients with COVID-19 with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and patients with severe COVID-19, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Consistently, hamsters' response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species. This work was supported by German Federal Ministry of Education and Research, (BMBF) grant IDs: 01ZX1304B, 01ZX1604B, 01ZX1906A, 01ZX1906B, 01KI2124, 01IS18026B and German Research Foundation (DFG) grant IDs: 14933180,431232613.

Comparative analysis of optional hunting behavior in Cricetinae hamsters using the data compression approach

Research into the hunting behavior in members of the Cricetidae family offers an opportunity to reveal what changes in the predatory behavioral sequences occur when a rodent species shifts from an omnivorous to a predatory lifestyle. The study tests the following hypotheses: are there phylogenetic differences in the divergence of species’ predatory lifestyles in hamsters or do ecological factors lead to shaping their hunting behavior? We applied the data compression approach for performing comparative analysis of hunting patterns as biological “texts.” The study presents a comparative analysis of hunting behaviors in five Cricetinae species, focusing on the new data obtained for the desert hamster Phodopus roborovskii whose behavior has never been studied before. The hunting behavior of P. roborovskii appeared to be the most variable one. In contrast, behavioral sequences in P. campbelli and Allocricetulus curtatus display more significant order and predictability of behavior during hunting. Optional hunting behavior in the most ancient species P. roborovskii displayed similarities with obligate patterns in “young” Allocricetulus species. It thus turned out to be the most advanced hunter among members of the Phodopus genus. Differences in hunting sequences among Phodopus representatives suggest that the hunting behavior of these species, despite its optional mode, was subject to selection during species splitting within the genus. These results did not reveal the role played by phylogenetic differences in the divergence of species’ predatory lifestyles. They suggested that ecological conditions are the main factors in speciation of the hunting behavior in hamsters.

The Spatial Niche and Influencing Factors of Desert Rodents.

Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs in two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model. Dwarf hamsters treated with either drug survive VOC omicron infection with equivalent lung titer reduction. Viral RNA copies in the upper respiratory tract of female ferrets receiving 1.25 mg/kg molnupiravir twice-daily are not significantly reduced, but infectious titers are lowered by >2 log orders and direct-contact transmission is stopped. Female ferrets dosed with 20 or 100 mg/kg nirmatrelvir/ritonavir twice-daily show 1–2 log order reduction of viral RNA copies and infectious titers, which correlates with low nirmatrelvir exposure in nasal turbinates. Virus replication resurges towards nirmatrelvir/ritonavir treatment end and virus transmits efficiently (20 mg/kg group) or partially (100 mg/kg group). Prophylactic treatment with 20 mg/kg nirmatrelvir/ritonavir does not prevent spread from infected ferrets, but prophylactic 5 mg/kg molnupiravir or 100 mg/kg nirmatrelvir/ritonavir block productive transmission. These data confirm reports of similar efficacy in older adults and inform on possible epidemiologic benefit of antiviral treatment.

Early protective effect of a ("pan") coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease. We generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms. Using HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies. PanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo.

Postmortem Diagnostic Imaging to Evaluate Idiopathic Hypertrophic Cardiomyopathy in a Roborovski Hamster

Idiopathic cardiomyopathy in hamsters can cause death due to cardiac failure. The current case study investigated the capability of imaging to reveal possible cardiomyopathy in a dead hamster. To this end, the cadaver of a 6-month-old male Roborovski dwarf hamster, which showed acute respiratory symptoms a few days before its death, was examined by virtopsy to discover the cause of death. Postmortem radiography was not efficient enough to evaluate the heart due to postmortem lung atelectasis that increases lung opacity and diminishes the contrast between lung and heart. Postmortem computed tomography can be helpful for the assessment of cardiac size. Consistent with postmortem echocardiographic studies, an increased thickness of the left ventricular parietal wall and the interventricular septum and dilation of the left atrium were observed. Thus, hypertrophic cardiomyopathy was determined by imaging and confirmed by the conventional necropsy approach. It showed that the cause of death was acute cardiac failure following idiopathic hypertrophic cardiomyopathy.

Similar adaptative mechanism but divergent demographic history of four sympatric desert rodents in Eurasian inland

Phenotypes associated with metabolism and water retention are thought to be key to the adaptation of desert species. However, knowledge on the genetic changes and selective regimes on the similar and divergent ways to desert adaptation in sympatric and phylogenetically close desert organisms remains limited. Here, we generate a chromosome level genome assembly for Northern three-toed jerboa (Dipus sagitta) and three other high-quality genome assemblies for Siberian jerboa (Orientallactaga sibirica), Midday jird (Meriones meridianus), and Desert hamster (Phodopus roborovskii). Genomic analyses unveil that desert adaptation of the four species mainly result from similar metabolic pathways, such as arachidonic acid metabolism, thermogenesis, oxidative phosphorylation, insulin related pathway, DNA repair and protein synthesis and degradation. However, the specific evolved genes in the same adaptative molecular pathway often differ in the four species. We also reveal similar niche selection but different demographic histories and sensitivity to climate changes, which may be related to the diversified genomic adaptative features. In addition, our study suggests that nocturnal rodents have evolved some specific adaptative mechanism to desert environments compared to large desert animals. Our genomic resources will provide an important foundation for further research on desert genetic adaptations.

SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model

SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.

De Novo-Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome: An Animal Model for Severe/Critical COVID-19.

The Roborovski dwarf hamster Phodopus roborovskii belongs to the Phodopus genus, one of the seven within Cricetinae subfamily. Like other rodents such as mice, rats, or ferrets, hamsters can be important animal models for a range of diseases. Whereas the Syrian hamster from the genus Mesocricetus is now widely used as a model for mild-to-moderate coronavirus disease 2019, Roborovski dwarf hamster shows a severe-to-lethal course of disease upon infection with the novel human coronavirus severe acute respiratory syndrome coronavirus 2.

Demography, disorders and mortality of pet hamsters under primary veterinary care in the United Kingdom in 2016.

Hamsters are popular pets worldwide but there is limited evidence on the overall health issues of pet hamsters. This study aimed to characterise the demography, disorder prevalence and mortality of pet hamsters in the United Kingdom. The VetCompass study included anonymised clinical records of 16,605 hamsters. The most common hamster species were Syrian (golden) (Mesocricetus auratus) (n=12,197, 73.45%), Djungarian (winter white dwarf) (Phodopus sungorus) (2286, 13.77%) and Roborovski hamsters (Phodopus roborovskii) (1054, 6.35%). The most prevalent precise-level disorders recorded across all hamsters were a presentation categorised as 'wet tail' (n=293, 7.33%), disorder undiagnosed (292, 7.30%), bite injuries from other hamsters (235, 5.88%), overgrown nail(s) (165, 4.13%), overgrown incisor(s) (159, 3.98%) and traumatic injury (152, 3.80%). The most prevalent disorders groups across all species of hamster were traumatic injury (n=616, 15.41%), enteropathy (450, 11.26%), ophthalmological disorder (445, 11.13%), skin disorder (362, 9.05%) and mass (361, 9.03%). The median age at death across all hamsters was 1.75 years (interquartile range: 0.83 to 2.20, range: 0.01 to 3.65). The most common causes of death at a precise level were wet tail (7.88%, 95% confidence interval: 6.35 to 9.66), abdominal mass (6.40%, 95% confidence interval: 5.01 to 8.03), neoplasia (5.38%, 95% confidence interval: 4.11 to 6.90) and dyspnoea (3.99%, 95% confidence interval: 2.9 to 5.34). This study provides veterinary professionals, educators, welfare scientists and owners with an evidence base on pet hamster health. A greater understanding of the common disorders of pet hamsters can support veterinary professionals to communicate more effectively with owners on key issues and outcomes to expect from hamster ownership.

Ultradian Near 2-4-h Rhythms of Body Temperature in Laboratory Rodents Depend on External Environmental Heliogeophysical Factor Reflected by Neutron Monitor Count Rate.

The study collated oscillations of body temperature of С57BL/6 mice and Roborovski hamsters (Phodopus roborovskii) in the period range of 100-240 min and fluctuations of the secondary cosmic rays reflected by neutron count rate of a neutron monitor at the Earth's surface. Cross-correlation of body temperature and neutron count rate data revealed their strong association only for simultaneous measurements. Collation of the phase of neutron count rate fluctuations with maxima of body temperature oscillations revealed the coincidence of the phases of both processes. There was a temporary connection between the periods of body temperature elevation and neutron count rate rise. Thus, not only the spectral parameters of biological and physical processes, but also their phases coincided, which corroborates the hypothesis on stimulating effect of increasing neutron count rate on activity of the animals.

Hamster models of COVID-19 pneumonia reviewed: How human can they be?

The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Syrian hamster (Mesocricetus auratus) rapidly developed into a popular model. It recapitulates many characteristic features as seen in patients with a moderate, self-limiting course of the disease such as specific patterns of respiratory tract inflammation, vascular endothelialitis, and age dependence. Among 4 other hamster species examined, the Roborovski dwarf hamster (Phodopus roborovskii) more closely mimics the disease in highly susceptible patients with frequent lethal outcome, including devastating diffuse alveolar damage and coagulopathy. Thus, different hamster species are available to mimic different courses of the wide spectrum of COVID-19 manifestations in humans. On the other hand, fewer diagnostic tools and information on immune functions and molecular pathways are available than in mice, which limits mechanistic studies and inference to humans in several aspects. Still, under pandemic conditions with high pressure on progress in both basic and clinically oriented research, the Syrian hamster has turned into the leading non-transgenic model at an unprecedented pace, currently used in innumerable studies that all aim to combat the impact of the virus with its new variants of concern. As in other models, its strength rests upon a solid understanding of its similarities to and differences from the human disease, which we review here.

Roborovski hamster (Phodopus roborovskii) strain SH101 as a systemic infection model of SARS-CoV-2

ABSTRACT Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 representing most aspects of the clinical manifestations of COVID-19 with systemic symptoms. Here we report that a Roborovski hamster strain SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection upon SARS-CoV-2 infection as in the case of the human counterpart, unlike current COVID-19 animal models. Roborovski hamster strain SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, labored breathing, dyspnea, cough, hunched posture, progressive weight loss, ruffled fur, and high fever following shaking chills. Histological examinations also revealed initial right-predominated pneumonia as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection in human, this hamster model seems to provide an ideal tool to investigate COVID-19.

Spermatogenesis in the Roborovski hamster (Phodopus roborovskii) and the Chinese hamster (Cricetulus griseus).

Spermatogenesis is an elaborately organized and tightly regulated differentiation process. The spermatogenesis duration is stable within a certain species but highly variable between species of the same family. In this study, the spermatogenesis duration of the Roborovski hamster was measured for the first time, and the spermatogenesis duration of the Chinese hamster was re-assessed. Stage classification and cycle length measurement were carried out by labeling the dividing cells with bromodeoxyuridine and an antibody-based chromogen as well as with the periodic acid-Schiff/hematoxylin stain. Analysis was conducted using reference calculation and linear regression. Morphological measurements completed our set of methods. The mean duration of one seminiferous epithelium cycle was 8.58±0.34days (mean±SEM; Phodopus roborovskii) and 16.59±0.47days (Cricetulus griseus) based on the reference calculation. Slightly higher results were obtained using linear regression analysis: 9.72±0.41days for P.roborovskii and 17.64±0.61days for C.griseus. Additionally, a newly developed exemplary flowchart was proposed for the Roborovski hamster to facilitate spermatogenesis stage classification also in other species. The Chinese hamster presented an unexpectedly high paired epididymides weight of 1.701±0.046g (mean±SEM) although having a body weight of only 40.5±0.7g. However, no significant correlation between the relative epididymis weight and spermatogenesis duration in mammals (Spearman rank correlation: r=-0.119, p=0.607, n=21) or rodents could be found (r=0.045, p=0.903, n=11). Our data emphasize the stability of the spermatogenesis duration within species and its remarkable variability between species. Further research is needed to identify the principal mechanisms and selection drivers that are responsible for such stability within species and the variability between species.

First Report of Phodopus sungorus Papillomavirus Type 1 Infection in Roborovski Hamsters (Phodopus roborovskii).

Papillomaviruses (PVs) are considered highly species-specific with cospeciation as the main driving force in their evolution. However, a recent increase in the available PV genome sequences has revealed inconsistencies in virus–host phylogenies, which could be explained by adaptive radiation, recombination, host-switching events and a broad PV host range. Unfortunately, with a relatively low number of animal PVs characterized, understanding these incongruities remains elusive. To improve knowledge of biology and the spread of animal PV, we collected 60 swabs of the anogenital and head and neck regions from a healthy colony of 30 Roborovski hamsters (Phodopus roborovskii) and detected PVs in 44/60 (73.3%) hamster samples. This is the first report of PV infection in Roborovski hamsters. Moreover, Phodopus sungorus papillomavirus type 1 (PsuPV1), previously characterized in Siberian hamsters (Phodopus sungorus), was the only PV detected in Roborovski hamsters. In addition, after a detailed literature search, review and summary of published evidence and construction of a tanglegram linking the cladograms of PVs and their hosts, our findings were discussed in the context of available knowledge on PVs described in at least two different host species.

A morphometric comparison of the cranial shapes of Asian dwarf hamsters (Phodopus, Cricetinae, Rodentia)

Phodopus is the smallest cricetine genus, consisting of the dwarf hamsters (Phodopus sungorus, Phodopus campbelli, and Phodopus roborovskii) of arid central and east Asia. Persistent taxonomic issues in this genus include (1) whether P. sungorus and P. campbelli are con- or heterospecific and (2) whether P. roborovskii is con- or heterogeneric with the aforementioned species. To shed new light on these questions, the crania of Phodopus species were compared to each other using geometric morphometrics. Furthermore, to determine what cranial traits are shared by Phodopus crania, they were compared to the more ‘typical’ small hamster Nothocricetulus migratorius. The three Phodopus species significantly differed in cranial size and shape from each other and from N. migratorius. A large part of shape variation was allometric with only weak evidence for unique allometries. All four species lacked sexual dimorphism in cranial size and shape. As a genus, Phodopus is characterized by small-sized crania, that are broad, short, and with flaring zygomatic arches. They also have reduced rostra and enlarged foramina magna. P. roborovskii was the most distinct Phodopus, characterized by its smaller-sized cranium, with greater breadth, a rounder braincase and orbit, a shorter incisive foramen and rostrum, a larger foramen magnum, and smaller bulla with a longer eustachian tube. The crania of P. sungorus and P. campbelli are very similar, but they do diverge in relatively minor (statistically nonsignificant) features, such as cranial roundness, as well as the size of the molar row, bulla, zygomatic arch, and incisive foramen. Shape differences conformed to phylogenetic distance and with habitat differences.

<i>Phodopus roborovskii </i>SH101 as a Systemic Infection Model of SARS-CoV-2

SARS-CoV-2 frequently causes systemic infection by breaking the bounds of the respiratory systems. Although the development of animal models recapitulating the clinical manifestations of systemic COVID-19 is of utmost importance to understand its pathogenesis, there has not been developed an animal model for systemic infection of SARS-CoV-2. Here we report that Phodopus roborovskii SH101, a laboratory inbred hamster strain of P. roborovskii, infected with SARS-CoV-2 breached the bounds of the respiratory system infection causing systemic infection as in the case of the human counterpart. P. roborovskii SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, dyspnea, cough, labored breathing, hunched posture, progressive weight loss, and ruffled fur, in addition to high fever accompanied by shaking chills. Histological examinations also revealed a serious right-predominated pneumonia as well as slight organ damages in the brain and liver as in the case of human systemic COVID-19 cases. Funding Statement: This research was supported by JINIS BDRD Research Institute of JINIS Biopharmaceuticals Inc. (Korea). Declaration of Interests: Authors declare no competing interests. Ethics Approval Statement: All procedures involving the mice and hamsters were accredited with the approval of the Institutional Animal Care and Use Committee (IACUC), in compliance with the guidelines of the Ethics Committee of Jeonbuk National University Laboratory Animal Center Guidelines on the Care and Use of Animals for Scientific Purposes. All animal experiments in this study were in accordance with the ARRIVE guidelines and checklist. All the animals used in this research were handled in a manner consistent with CDC/ABSA/WHO guidelines for the prevention of human infection with the SARS-CoV-2 virus.

Animal models of COVID-19 hyper-inflammation.

Animal models of COVID-19 hyper-inflammation.

The Roborovski Dwarf Hamster Is A Highly Susceptible Model for a Rapid and Fatal Course of SARS-CoV-2 Infection

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated an unprecedented and yet-unresolved health crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, few species examined so far develop robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, we compare the susceptibilities of three dwarf hamster species (Phodopus spp.) to SARS-CoV-2 and introduce the Roborovski dwarf hamster (P. roborovskii) as a highly susceptible COVID-19 model with consistent and fulminant clinical signs. Particularly, only this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection but not reproduced in any experimentally infected animal. Based on our findings, we propose the Roborovski dwarf hamster as a valuable model to examine the efficacy and safety of vaccine candidates and therapeutics, particularly for use in highly susceptible individuals.

The Roborovski Dwarf Hamster – A Highly Susceptible Model for a Rapid and Fatal Course of SARS-CoV-2 Infection

The COVID-19 pandemic caused by SARS-CoV-2 has precipitated an unprecedented and yet unresolved crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, no species examined so far develops robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, we compare the susceptibility of three dwarf hamster species (Phodopus spp.) to SARS-CoV-2 and introduce the Roborovski dwarf hamster (P. roborovskii) as a highly susceptible COVID-19 model with consistent and fulminant clinical signs. Particularly, this species shows SARS-CoV-2-induced severe acute diffuse alveolar damage and hyaline microthrombi in the lungs, changes described in patients who succumbed to the infection, but so far not reproduced in any experimentally infected animal. We therefore propose the Roborovski dwarf hamster as an ideal model to examine the efficacy and safety of live attenuated vaccine candidates and novel therapeutics, particularly for their use in highly susceptible individuals.