Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review
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Abstract
Background
Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19.
Methods
We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19.
Result
Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates ( n = 13), mice ( n = 7), ferrets ( n = 4), hamsters ( n = 4), and cats ( n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy.
Conclusions
Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.
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SciScore for 10.1101/2020.04.10.022103: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: This study was approved by the Institutional Review Board on Ethics Committee of BGI (permit no. BGI-IRB19125). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Collection of monkey tissues: A 6-year old female cynomolgus monkey was purchased from Huazhen Laboratory Animal Breeding Centre (Guangzhou, China). Table 2: Resources
Software and Algorithms Sentences Resources Single-cell RNA-seq data processing: Raw sequencing reads from DIPSEQ-T1 were filtered and demultiplexed using PISA (version 0.2) (https://github.com/shiquan/PISA). PISAsuggested: (PISA, RRID:SCR_015749)Reads were aligned to … SciScore for 10.1101/2020.04.10.022103: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics statement: This study was approved by the Institutional Review Board on Ethics Committee of BGI (permit no. BGI-IRB19125). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Collection of monkey tissues: A 6-year old female cynomolgus monkey was purchased from Huazhen Laboratory Animal Breeding Centre (Guangzhou, China). Table 2: Resources
Software and Algorithms Sentences Resources Single-cell RNA-seq data processing: Raw sequencing reads from DIPSEQ-T1 were filtered and demultiplexed using PISA (version 0.2) (https://github.com/shiquan/PISA). PISAsuggested: (PISA, RRID:SCR_015749)Reads were aligned to Macaca_fascicularis_5.0 genome using STAR (version 2.7.4a)46 and sorted by sambamba (version 0.7.0)47. STARsuggested: (STAR, RRID:SCR_015899)Cell clustering and identification of cell types: Clustering analysis of the complete cynomolgus monkey tissue dataset was performed using Scanpy (version 1.4)48 in a Python environment. Pythonsuggested: (IPython, RRID:SCR_001658)Each tissue dataset was portrayed using the Seurat package (version 3.1.1)49 in R environment by default parameters for filtering, data normalization, dimensionality reduction, clustering, and gene differential expression analysis. Seuratsuggested: (SEURAT, RRID:SCR_007322)To infer the biological function of highly correlated genes (cor > 0.6 and adjusted P value < 0.001), we performed gene set enrichment analysis using Metascape ( Metascapesuggested: (Metascape, RRID:SCR_016620)Results from OddPub: Thank you for sharing your code and data.
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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