Abstract: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… Show more
“…Furthermore, some common COVID-19 signs such as anosmia and ageusia have been reported at markedly lower prevalence (i.e., 8.3% and 9%) compared to pre-Omicron reports (38.2% & 36.6%) (Mutiawati et al ., 2021; Maisa et al ., 2022). Syrian hamsters are a well-established animal model that have proven to be an excellent platform to evaluate efficacy of vaccines and therapeutics for SARS-CoV-2 and mimic many clinicopathologic hallmarks of moderate self-limiting disease in humans (Imai et al ., 2020; Gruber et al ., 2021). However, this model is not without limitations.…”
Coronavirus disease 2019 continues to batter the world with the unceasing introduction of new variants of the causative virus, SARS-CoV-2. In order to understand differences in disease caused by variants of concern and to develop variant-specific vaccines, suitable small animal models are required that mimic disease progression in humans at various stages of life. In this study, we compared the dynamics of infection with two SARS-CoV-2 variants of concern (Delta and Omicron) in aged (>1 year 3 months old) and young (<5 weeks old) Syrian hamsters (Mesocricetus auratus). We show that no weight loss occurred in Omicron infected groups regardless of age, while infection with the Delta variant caused weight loss of up to 10% by day 7 post-infection with slower and incomplete recovery in the aged group. Omicron replicated to similar levels as Delta in the lungs, trachea and nasal turbinates, with no significant differences in the tissue viral loads of aged versus young animals for either variant. In contrast to rare necrosis observed in Omicron-infected animals regardless of age, severe necrosis was observed in the olfactory epithelium in Delta-infected animals. Omicron infection also resulted in mild pulmonary disease in both young and aged animals compared to the moderate acute necrotizing bronchointerstitial pneumonia seen in Delta-infected animals. These results suggest that Omicron infection results in an attenuated clinical disease outlook in Syrian hamsters compared to infection with the Delta variant irrespective of age.
“…Furthermore, some common COVID-19 signs such as anosmia and ageusia have been reported at markedly lower prevalence (i.e., 8.3% and 9%) compared to pre-Omicron reports (38.2% & 36.6%) (Mutiawati et al ., 2021; Maisa et al ., 2022). Syrian hamsters are a well-established animal model that have proven to be an excellent platform to evaluate efficacy of vaccines and therapeutics for SARS-CoV-2 and mimic many clinicopathologic hallmarks of moderate self-limiting disease in humans (Imai et al ., 2020; Gruber et al ., 2021). However, this model is not without limitations.…”
Coronavirus disease 2019 continues to batter the world with the unceasing introduction of new variants of the causative virus, SARS-CoV-2. In order to understand differences in disease caused by variants of concern and to develop variant-specific vaccines, suitable small animal models are required that mimic disease progression in humans at various stages of life. In this study, we compared the dynamics of infection with two SARS-CoV-2 variants of concern (Delta and Omicron) in aged (>1 year 3 months old) and young (<5 weeks old) Syrian hamsters (Mesocricetus auratus). We show that no weight loss occurred in Omicron infected groups regardless of age, while infection with the Delta variant caused weight loss of up to 10% by day 7 post-infection with slower and incomplete recovery in the aged group. Omicron replicated to similar levels as Delta in the lungs, trachea and nasal turbinates, with no significant differences in the tissue viral loads of aged versus young animals for either variant. In contrast to rare necrosis observed in Omicron-infected animals regardless of age, severe necrosis was observed in the olfactory epithelium in Delta-infected animals. Omicron infection also resulted in mild pulmonary disease in both young and aged animals compared to the moderate acute necrotizing bronchointerstitial pneumonia seen in Delta-infected animals. These results suggest that Omicron infection results in an attenuated clinical disease outlook in Syrian hamsters compared to infection with the Delta variant irrespective of age.
“…The Syrian hamster (M. auratus) rapidly developed into a popular model. However, among other hamsters, Roborovski dwarf hamster (P. roborovskii) more closely mimics the disease with frequent lethal outcomes (Gruber et al, 2021). So, different hamster species should be used to study different courses of COVID-19 manifestations.…”
The ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 is associated with high morbidity and mortality. This zoonotic virus has emerged in Wuhan of China in December 2019 from bats and pangolins probably and continuing the human‐to‐human transmission globally since last two years. As there is no efficient approved treatment, a number of vaccines were developed at an unprecedented speed to counter the pandemic. Moreover, vaccine hesitancy is observed that may be another possible reason for this never ending pandemic. In the meantime, several variants and mutations were identified and causing multiple waves globally. Now the safety and efficacy of these vaccines are debatable and recommended to determine whether vaccines are able to interrupt transmission of SARS‐CoV‐2 variant of concern (VOC). Moreover, the VOCs continue to emerge that appear more transmissible and less sensitive to virus‐specific immune responses. In this overview, we have highlighted various drugs and vaccines used to counter this pandemic along with their reported side effects. Moreover, the preliminary data for the novel VOC “Omicron” are discussed with the existing animal models.
“…By contrast, Syrian golden hamsters infected with SARS-CoV-2 develop transient pneumonia but do not recapitulate hallmark features of life-threatening severe COVID-19. Disease typically remains mild-to-asymptomatic in golden hamsters and animals fully recover within two weeks 20 . Lethal disease with severe histopathology affecting lung, liver, and kidney can be induced in transgenic K18-hACE2 mice expressing human ACE2, but organ distribution of the receptor is non-physiological, resulting in rapid neuro-invasion of the virus and the development of acute, lethal viral encephalitis 21 , which is not seen in human patients.…”
SARS-CoV-2 variants of concern (VOC) have triggered distinct infection waves in the coronavirus disease 2019 (COVID-19) pandemic, culminating in currently all-time high incidence rates of VOC omicron. Orally available direct-acting antivirals such as molnupiravir promise to improve disease management and limit SARS-CoV-2 spread. However, molnupiravir efficacy against VOC delta was questioned based on clinical trial results and its potency against omicron is unknown. This study evaluates molnupiravir against a panel of relevant VOC in three efficacy models: primary human airway epithelium organoids, the ferret model of upper respiratory disease, and a lethal Roborovski dwarf hamster efficacy model of severe COVID-19-like acute lung injury. All VOC were equally efficiently inhibited by molnupiravir in cultured cells and organoids. Treatment consistently reduced upper respiratory VOC shedding in ferrets and prevented viral transmission. Pathogenicity in the dwarf hamsters was VOC-dependent and highest for gamma, omicron, and delta with fulminant lung histopathology. Oral molnupiravir started 12 hours after infection resulted in complete survival of treated dwarf hamsters independent of challenge VOC. However, reduction in lung virus differed VOC-dependently, ranging from one (delta) to four (gamma) orders of magnitude compared to vehicle-treated animals. Dwarf hamsters infected with VOC omicron showed significant individual variation in response to treatment. Virus load reduction was significant in treated males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir seen in human trials and alerts that therapeutic benefit of approved antivirals must be continuously reassessed in vivo as new VOC emerge.
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