scholarly journals Isolation of SARS-CoV-2 B.1.1.28.2 P2 variant and pathogenicity comparison with D614G variant in hamster model

2021 ◽  
Author(s):  
Pragya Yadav ◽  
Sreelekshmy Mohandas ◽  
Prasad Sarkale ◽  
Dimpal Nyayanit ◽  
Anita Shete ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Potential Threat ◽  
Hamster Model ◽  
Fold Reduction ◽  
Variant Virus ◽  
Genomic Characterization ◽  
Generation Sequencing ◽  
Severe Lung

Background: Considering the potential threat from emerging SARS-CoV-2 variants and the rising COVID-19 cases, SARS-CoV-2 genomic surveillance is ongoing in India. We report herewith the isolation of the P.2 variant (B.1.1.28.2) from international travelers and further its pathogenicity evaluation and comparison with D614G variant (B.1) in hamster model. Methods: Virus isolation was performed in Vero CCL81 cells and genomic characterization by next generation sequencing. The pathogenicity of the isolate was assessed in Syrian hamster model and compared with B.1 variant. Results: B.1.1.28.2 variant was isolated from nasal/throat swabs of international travelers returned to India from United Kingdom and Brazil. The B.1.1.28.2 variant induced body weight loss, viral replication in the respiratory tract, lung lesions and caused severe lung pathology in infected Syrian hamster model in comparison, with B.1 variant infected hamsters. The sera from B.1.1.28.2 infected hamsters efficiently neutralized the D614G variant virus whereas 6-fold reduction in the neutralization was seen in case of D614G variant infected hamsters sera with the B.1.1.28.2 variant. Conclusions: B.1.1.28.2 lineage variant could be successfully isolated and characterization could be performed. Pathogenicity of the isolate was demonstrated in Syrian hamster model and in comparison, with B.1 variant was found more pathogenic. The findings of increased disease severity and neutralization reduction is of great concern and point towards the need for screening the vaccines for efficacy.

scholarly journals Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory ◽  
Prophylactic Use

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.

scholarly journals Comparison of the pathogenicity and virus shedding of SARS CoV-2 VOC 202012/01 and D614G variant in hamster model

2021 ◽  
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya D Yadav ◽  
Dimpal Nyayanit ◽  
Gururaj Deshpande ◽  
Anita Shete-Aich ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Virus Shedding ◽  
Vaccination Programs

AbstractThe emergence of SARS-CoV-2 variants has posed a serious challenge to public health system and vaccination programs across the globe. We have studied the pathogenicity and virus shedding pattern of the SARS-CoV-2 VOC 202012/01 and compared with D614G variant in Syrian hamsters. VOC 202012/01 could produce disease in hamsters characterized by body weight loss and respiratory tract tropism but mild lung pathology. Further, we also documented that neutralizing antibodies developed against VOC 202012/01 could equally neutralize D614G variant. Higher load of VOC 202012/01 in the nasal wash specimens was observed during the first week of infection outcompeting the D614G variant. The findings suggest increased fitness of VOC 202012/01 to the upper respiratory tract which could lead to higher transmission. Further investigations are needed to understand the transmissibility of new variants.One-Sentence SummarySARS-CoV-2 VOC 202012/01 infected hamsters demonstrated high viral RNA shedding through the nasal secretions and significant body weight loss with mild lung pathology compared to the D614G variant.

scholarly journals Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility

2020 ◽  
Author(s):  
Jasper Fuk-Woo Chan ◽  
Anna Jinxia Zhang ◽  
Shuofeng Yuan ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Viral Load ◽  
Syrian Hamster ◽  
Clinical Signs ◽  
Neutralizing Antibody ◽  
Adaptive Mutation ◽  
Lung Pathology ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Virus Challenge

Abstract Background A physiological small-animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer. Results The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 105 and 107 TCID50/g. Challenged index hamsters consistently infected naive contact hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralizing antibody titers ≥1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected hamsters. Conclusions Besides satisfying Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.

scholarly journals Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 824
Author(s):  
Nora M. Gerhards ◽  
Jan B. W. J. Cornelissen ◽  
Lucien J. M. van Keulen ◽  
José Harders-Westerveen ◽  
Rianka Vloet ◽  
...  
Keyword(s):  
Animal Species ◽  
Body Weight Loss ◽  
Activity Wheel ◽  
Lung Pathology ◽  
Research Groups ◽  
Hamster Model ◽  
Single Experiment ◽  
Administration Routes ◽  
Precision Cut Lung Slices

In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment.

scholarly journals High-Fat High-Sugar Diet-Induced Changes in the Lipid Metabolism Are Associated with Mildly Increased COVID-19 Severity and Delayed Recovery in the Syrian Hamster

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2506
Author(s):  
Julia R. Port ◽  
Danielle R. Adney ◽  
Benjamin Schwarz ◽  
Jonathan E. Schulz ◽  
Daniel E. Sturdevant ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Metabolic Diseases ◽  
Lung Pathology ◽  
High Fat ◽  
Hamster Model ◽  
Viral Shedding ◽  
High Sugar ◽  
Lipid Response ◽  
Unhealthy Diet ◽  
Induced Changes

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.

scholarly journals Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19

2021 ◽  
Author(s):  
Thomas J Esparza ◽  
Yaozong Chen ◽  
Negin P Martin ◽  
Helle Bielefeldt-Ohmann ◽  
Richard A Bowen ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Low Cost ◽  
Unmet Need ◽  
Lung Pathology ◽  
Hamster Model ◽  
Angiotensin Converting Enzyme 2 ◽  
In Vitro Characterization ◽  
Pathological Disease

There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and in vitro characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad in vitro neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses, including the currently dominant Delta variant. The structure of NIH-CoVnb-112 bound to SARS-CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an in vivo pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection.

scholarly journals Western diet increases COVID-19 disease severity in the Syrian hamster

2021 ◽  
Author(s):  
Julia R Port ◽  
Danielle R Adney ◽  
Benjamin Schwarz ◽  
Jonathan Schulz ◽  
Daniel E Sturdevant ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Metabolic Diseases ◽  
Western Diet ◽  
Lung Pathology ◽  
Hamster Model ◽  
Viral Shedding ◽  
Lipid Response ◽  
Unhealthy Diet ◽  
Immunomodulatory Therapies ◽  
First Time

Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an increased trend of systemic IL-10 and IL-6, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.

scholarly journals Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Rajdeep Dalal ◽  
Srikanth Sadhu ◽  
Akshay Binayke ◽  
Jyotsna Dandotiya ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Troponin I ◽  
Late Phase ◽  
Cardiovascular Complications ◽  
Therapeutic Interventions ◽  
Wall Thickening ◽  
Lung Pathology ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Metabolic Marker

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.

scholarly journals Effect of Prophylactic Use of Intranasal Oil Formulations in the Hamster Model of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Histopathological Analysis ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in the upper respiratory tract, leading to coronavirus disease 2019 (COVID-19). Severe COVID-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting the entry of the virus or its internalization in the upper respiratory tract are of interest. Herein, we report the prophylactic application of two intranasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and til tailya, in the hamster model of SARS-CoV-2 infection. Prophylactic intra-nasal instillation of these oil formulations exhibited reduced viral load in lungs and resulted in reduced body weight loss and lung-pneumonitis. In line with reduced viral load, histopathological analysis revealed a reduction in lung pathology in the Anu oil group as compared to the control infected group. However, the til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokine genes, including Th1 and Th17 cytokines for both the intranasal formulations as a result of decreased viral load. Together, the prophylactic intranasal application of Anu oil seems to be useful in limiting both viral load and severity in SARS-CoV2 infection in the hamster model.

scholarly journals Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

2021 ◽  
Vol 17 (3) ◽  
pp. e1009383
Author(s):  
Drishya Kurup ◽  
Delphine C. Malherbe ◽  
Christoph Wirblich ◽  
Rachael Lambert ◽  
Adam J. Ronk ◽  
...  
Keyword(s):  
Immune Response ◽  
Weight Loss ◽  
Respiratory Failure ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Lung Pathology ◽  
Hamster Model ◽  
Rapid Spread ◽  
Asymptomatic Infections ◽  
Efficacious Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

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