Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extrapulmonary 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 (CVCs) 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, 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.
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SciScore for 10.1101/2021.01.11.426080: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The plates were incubated at room temperature (RT) for 1 h and then washed three times with washing buffer (PBS + 0.05 % tween 20), the ELISA plates with N protein coating was washed additionally once with high salt PBST (Phosphate buffer with 500 mM NaCl and 0.05 % Tween 20) and incubated with biotinylated anti-hamster IgG antibody (Sigma) for another 1 h and washed subsequently with the washing buffer and incubated further with Avidin-HRP (Sigma) for 45 min at RT. anti-hamster IgGsuggested: NoneAvidin-HRPsuggested: (Thermo Fisher Scientific Cat# ICN55898, RRID:AB_2334691)… SciScore for 10.1101/2021.01.11.426080: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The plates were incubated at room temperature (RT) for 1 h and then washed three times with washing buffer (PBS + 0.05 % tween 20), the ELISA plates with N protein coating was washed additionally once with high salt PBST (Phosphate buffer with 500 mM NaCl and 0.05 % Tween 20) and incubated with biotinylated anti-hamster IgG antibody (Sigma) for another 1 h and washed subsequently with the washing buffer and incubated further with Avidin-HRP (Sigma) for 45 min at RT. anti-hamster IgGsuggested: NoneAvidin-HRPsuggested: (Thermo Fisher Scientific Cat# ICN55898, RRID:AB_2334691)Experimental Models: Cell Lines Sentences Resources Briefly, serial dilutions of 10-folds from each sample were added to the wells containing Vero-E6 cells monolayer in DMEM media in quadruplicate. Vero-E6suggested: NoneThe tissue samples from 2 to 14 dpi were used to infect Vero E6 cell monolayers in 48-plates as described previously. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources Intracellular anti-mouse IFN-γ (XMG1.2) (BioLegend) staining was then carried out after fixing the cells in Cytofix solution and permeabilization with 1X Perm/Wash Buffer using kit (BD Biosciences; #554714) for 20 min in dark at RT. BD Biosciencessuggested: (BD Biosciences, RRID:SCR_013311)Cells were then washed and acquired on FACS Canto II and were analyzed with FlowJo software (Tree star) as previously described (Malik et al., 2017) FlowJosuggested: (FlowJo, RRID:SCR_008520)The web-based tool ClustVis was used to create the sample PCA plots to check the clustering of biological samples (ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap) (Metsalu and Vilo, 2015). ClustVissuggested: (ClustVis, RRID:SCR_017133)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2021.01.11.426080: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The plates were incubated at room temperature (RT) for 1 h and then washed three times with washing buffer (PBS + 0.05 % tween 20), the ELISA plates with N protein coating were washed additionally once with high salt PBST (Phosphate buffer with 500 mM NaCl and 0.05 % Tween 20) and incubated with biotinylated anti-hamster IgG antibody (Sigma) for another 1 h and washed subsequently with the washing buffer and incubated further with Avidin-HRP (Sigma) for 45 min at RT. …anti-hamster IgGsuggested: NoneSciScore for 10.1101/2021.01.11.426080: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources The plates were incubated at room temperature (RT) for 1 h and then washed three times with washing buffer (PBS + 0.05 % tween 20), the ELISA plates with N protein coating were washed additionally once with high salt PBST (Phosphate buffer with 500 mM NaCl and 0.05 % Tween 20) and incubated with biotinylated anti-hamster IgG antibody (Sigma) for another 1 h and washed subsequently with the washing buffer and incubated further with Avidin-HRP (Sigma) for 45 min at RT. anti-hamster IgGsuggested: NoneAvidin-HRPsuggested: (R and D Systems Cat# A-115, RRID:AB_10992927)Experimental Models: Cell Lines Sentences Resources Virus preparation and determination of viral titers SARS-Related Coronavirus 2, Isolate USA-WA1/2020 virus was used as challenge strain, which was grown and titrated in Vero E6 cell line grown in Dulbecco’s Modified Eagle Medium (DMEM) complete media containing 4.5 g/L D-glucose, 100,000 U/L Penicillin- Vero E6suggested: NoneTCID50 For TCID50 determination, 50 µl of homogenized lung supernatant samples were incubated with confluent Vero-E6 cells in 96-well plates as described previously (Chan et al., 2020). Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Intracelluar anti-mouse IFN-γ (XMG1.2) (BioLegend) staining was then carried out after fixing the cells in Cytofix solution and permeabilization with 1X Perm/Wash Buffer using kit (BD Biosciences; # 554714) for 20 min in dark at RT. BD Biosciencessuggested: (BD Biosciences, RRID:SCR_013311)Cells were then washed and acquired on FACS Canto II and were analysed with FlowJo software (Tree star) as previously described (Malik et al., 2017) FlowJosuggested: (FlowJo, RRID:SCR_008520)The web-based tool ClustVis was used to create the sample PCA plots to check the clustering of biological samples (ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap) (Metsalu and Vilo, 2015). ClustVissuggested: (ClustVis, RRID:SCR_017133)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap used on pages 6, 8, 12, 36, 47, 48, 49, 50 and 52. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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