Animal models for COVID-19: advances, gaps and perspectives

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is the causative agent of the novel coronavirus disease (COVID‐19) pandemic, which has caused serious challenges for public health systems worldwide. Due to the close relationship between animals and humans, confirmed transmission from humans to numerous animal species has been reported. Understanding the cross‐species transmission of SARS‐CoV‐2 and the infection and transmission dynamics of SARS‐CoV‐2 in different animals is crucial to control COVID‐19 and protect animal health. In this review, the possible animal origins of SARS‐CoV‐2 and animal species naturally susceptible to SARS‐CoV‐2 infection are discussed. Furthermore, this review categorizes the SARS‐CoV‐2 susceptible animals by families, so as to better understand the relationship between SARS‐CoV‐2 and animals.

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“…Dogs have low susceptibility to SARS‐CoV‐2, and their usefulness as a natural animal model for SARS‐CoV‐2 is somewhat limited. 94 , 97 …”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 and natural infection in animals

Qiu

Liu

Sha

2022

Journal of Medical Virology

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“…Natural and genetically modified species used to model different aspects of COVID-19 include mice, ferrets, cats, dogs, pigs, and non-human primates. [77][78][79][80][81] The models described for CSS include the Staphylococcal superantigen mutant model in rabbits, 82 the hemolytic transfusion model in mice, 83 and the reactions of dogs to anti-CD28 mAb, 84 or primates to simian immunodeficiency virus, 85 or pigs to a virulent African swine fever virus. 86 .…”

Section: Discussionmentioning

confidence: 99%

Zymosan-induced leukocyte and cytokine changes in pigs: a new model for streamlined drug testing against severe COVID-19

Kökény

Bakos

Barta

et al. 2022

Preprint

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Injection of 0.1 mg/kg zymosan in pigs i.v. elicited transient hemodynamic disturbance within minutes, without major blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This change was followed by a transient granulopenia with a trough at 1 h, and then, up to about 6 h, a major granulocytosis, resulting in a 3-4-fold increase of neutrophil-to-lymphocyte ratio (NLR). In parallel with the changes in WBC differential, qRT-PCR and ELISA analyses showed increased transcription and/or release of inflammatory cytokines and chemokines into blood, including IL-6, TNF-α, CCL-2, CXCL-10, and IL-1RA. The expression of IL-6 peaked at already 1.5-2.5 h, and we observed significant correlation between lymphopenia and IL-6 gene expression. While these changes are consistent with zymosan's known stimulatory effect on both the humoral and cellular arms of the innate immune system, what gives novel clinical relevance to the co-manifestation of above hemodynamic, hematological, and immune changes is that they represent independent bad prognostic indicators in terminal COVID-19 and other diseases involving cytokine storm. Thus, within a 6 h experiment, the model enables consecutive reproduction of a symptom triad that is characteristic of late-stage COVID-19. Given the limitations of modeling cytokine storm in animals and effectively treating severe COVID-19, the presented relatively simple large animal model may advance the R&D of drugs against these conditions. One of these disease markers (NLR), obtained from a routine laboratory endpoint (WBC differential), may also enable streamlining the model for high throughput drug screening.

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“…Proper animal models for coronavirus disease 19 (COVID-19) are crucial to uncover disease mechanisms and develop appropriate vaccines and drugs. To determine the best model for studying COVID-19, a wide range of animals, including captive and wild animals (deer, lions, and gorillas), companion animals (cats and dogs), farm animals (pigs, chickens, ducks, and mink), and experimental animals (nonhuman primates, mice, hamsters, ferrets, and Chinese tree shrews), have been used to study susceptibility to SARS-CoV-2 infection, with each model harboring its own advantages and disadvantages ( Fan et al, 2022 ; Muñoz-Fontela et al, 2020 ). Among these COVID-19 models, rhesus macaques well mimic the pathological characteristics of human patients; hamsters are the most suitable for understanding transmission of SARS-CoV-2; and human angiotensin-converting enzyme 2 ( hACE2 ) transgenic mice are the most widely used for vaccine and drug evaluation ( Fan et al, 2022 ).…”

Section: Dear Editormentioning

confidence: 99%

Infectivity of SARS-CoV-2 and protection against reinfection in rats

Long

et al. 2022

Zoological Research

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A: Schematic of infection experiments. B: Alterations in body weight in rats with (infection group) or without (mock group) SARS-CoV-2 infection. Data are mean±standard error of the mean ( SEM ). C: Viral RNA levels in throat swabs of infected rats at 1 dpi ( n =32), 3 dpi ( n =24), and 5 dpi ( n =16). Each dot indicates log copies of viral genomic N gene (top), E gene (middle), and subgenomic E (sgE) gene (bottom) per swab from an individual rat. D: Viral RNA levels in lungs of infected rats at 1, 3, and 5 dpi. Each red circle (1 dpi, n =8), blue square (3 dpi, n =8), and black triangle (5 dpi, n =8) refers to log viral RNA copies/µg total RNA of lung lobe of an individual rat. E: Gross pathological lung specimens at indicated time points after SARS-CoV-2 infection. F: Hematoxylin/eosin (H&E) staining of the lung sections in SARS-CoV-2-infected rats showing lesions with thickened alveolar septa and infiltration of lymphocytes. Scale bar: 100 µm. G: Immunohistochemical analysis of SARS-CoV-2 N protein in rat lung tissues on 1 dpi. Scale bar: 1 mm for entire lung lobe section (top), 50 µm for enlarged view of boxed areas labeled by numbers in entire section (bottom). H, I: Viral RNA loads in throat swabs (H) and nasal turbinate (I) of rats re-challenged with SARS-CoV-2 for 1 day (1 dpr, n =8) were significantly lower than in initial infection group rats (1 dpi, n =5). * : P <0.05; *** : P <0.001; two-tailed Student’s t -test. J: Viral RNA levels in lungs of infected rats at 1 dpi (initial infection group) and 1 dpr (reinfection group). K: Neutralizing antibody (NAb) titers in SARS-CoV-2-infected rats for protection against re-challenge. Values in D, H, I, and J are presented as mean±standard deviation ( SD ). Dotted lines in C and H represent limit of quantification (250 copies/mL). Dotted lines in D, I, and J represent limit of quantification (8.7 copies/µg total RNA of lung).

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Animal models for COVID-19: advances, gaps and perspectives

Cited by 64 publications

References 342 publications

SARS‐CoV‐2 and natural infection in animals

SARS‐CoV‐2 and natural infection in animals

Zymosan-induced leukocyte and cytokine changes in pigs: a new model for streamlined drug testing against severe COVID-19

Infectivity of SARS-CoV-2 and protection against reinfection in rats

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