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 ◽  
...  

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.

2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Rajdeep Dalal ◽  
Srikant Sadhu ◽  
Yashwant Kumar ◽  
Tripti Shrivastava ◽  
...  

SummarySevere acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in golden Syrian hamster (GSH) causes lung pathology and resembles human coronavirus disease (Covid-19). However, extra-pulmonary pathologies of SARS-CoV-2 infection that result in long Covid remains undefined in GSH. Here, using in silico modelling we show that hamster angiotensin-converting enzyme-2 (ACE-2) and neuropilin-1 (NRP-1) interaction with SARS-CoV-2 is similar to human. Intranasal SARS-CoV-2 infection in GSH resulted in early onset of lung pathologies marked by aggressive inflammatory response. Remarkably, late phase of SARS-CoV2 infection in GSH showed cardiovascular complications (CVC) characterized by ventricular hypertrophy, ventricular wall thickening, interstitial coronary fibrosis and altered lipidomics with elevated cholesterol, low-density lipoprotein and long chain fatty acid triglycerides. Moreover, serum metabolomics profile of infected GSH correlated with Covid19 patients. Together, we propose GSH as a suitable animal model to study immediate and long Covid19 pathologies that could be extended to therapeutics against Covid19 related CVC.


Author(s):  
Jasper Fuk-Woo Chan ◽  
Anna Jinxia Zhang ◽  
Shuofeng Yuan ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
...  

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.


2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
T IKEGAMI ◽  
P LATHAM ◽  
K KOBAYASHI ◽  
K ARIMORI ◽  
B BOUSCAREL

2022 ◽  
Author(s):  
Shuofeng Yuan ◽  
Zi-Wei Ye ◽  
Ronghui Liang ◽  
Kaiming Tang ◽  
Anna Jinxia Zhang ◽  
...  

The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.


2021 ◽  
Author(s):  
Linqi Zhang ◽  
Mingxi Li ◽  
Jingao Guo ◽  
Shuaiyao Lu ◽  
Runhong Zhou ◽  
...  

Abstract The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


2021 ◽  
Author(s):  
Kelvin Yeung ◽  
Wei Qiao ◽  
Hui En Lau ◽  
Hui Zhi Xie ◽  
Vincent Poon ◽  
...  

Abstract Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.


2020 ◽  
Vol 71 (16) ◽  
pp. 2139-2149 ◽  
Author(s):  
Jasper Fuk-Woo Chan ◽  
Shuofeng Yuan ◽  
Anna Jinxia Zhang ◽  
Vincent Kwok-Man Poon ◽  
Chris Chung-Sing Chan ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium- to large-sized respiratory droplets, although airborne transmission may be possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. Methods We used a well-established golden Syrian hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index hamsters and naive hamsters into closed system units each comprising 2 different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed between the cages was investigated. Besides clinical scoring, hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. Results Noncontact transmission was found in 66.7% (10/15) of exposed naive hamsters. Surgical mask partition for challenged index or naive hamsters significantly reduced transmission to 25% (6/24, P = .018). Surgical mask partition for challenged index hamsters significantly reduced transmission to only 16.7% (2/12, P = .019) of exposed naive hamsters. Unlike the severe manifestations of challenged hamsters, infected naive hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. Conclusions SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei which could be reduced by surgical mask partition in the hamster model. This is the first in vivo experimental evidence to support the possible benefit of surgical mask in prevention of COVID-19 transmission, especially when masks were worn by infected individuals.


2013 ◽  
Vol 61 (24) ◽  
pp. 5772-5782 ◽  
Author(s):  
Haiqiu Huang ◽  
Zhuohong Xie ◽  
Stephen M. Boue ◽  
Deepak Bhatnagar ◽  
Wallace Yokoyama ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2506
Author(s):  
Julia R. Port ◽  
Danielle R. Adney ◽  
Benjamin Schwarz ◽  
Jonathan E. Schulz ◽  
Daniel E. Sturdevant ◽  
...  

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.


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