Infection with Novel Coronavirus (SARS-CoV-2) Causes Pneumonia in the Rhesus Macaques

Shan, Chao; Yao, Yanfeng; Yang, Xing‐Lou; Zhou, Yiwu; Wu, Jia; Gao, Ge; Peng, Yun; Yang, Lian; Xiong, Ji; Jiang, Ren-Di; Zhang, Huajun; Gao, Xiaoxiao; Cheng, Peng; Min, Juan; Chen, Ying; Si, Hao-Rui; Zhou, Peng; Wang, Yan-Yi; Wei, Hongping; Pang, Wei; Hu, Zheng-Fei; Lv, Lei; Zheng, Yong‐Tang; Z, Shi; Yuan, Zhiming

doi:10.21203/rs.2.25200/v1

Cited by 81 publications

(102 citation statements)

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“…Experimental infection with SARS-CoV-2 in these models provides basic information to address a number of fundamental questions regarding its pathogenicity, the interaction with the different hosts and, hopefully, establishing the criteria for prevention and care. In line with observations in SARS models, non-human primates and wild-type mice infected with SARS-CoV-2 exhibit a relatively mild clinical disease, in spite of the evidence that Quantitative reverse transcription polymerase chain reaction (RT-qPCR) revealed a massive infection of the respiratory tract [44,45] (Table 2). Rhesus macaques infected with bronchoalveolar lavage fluid obtained from an affected patient developed a histopathologically confirmed interstitial pneumonia, associated with a widespread presence of SARS-CoV-2 in the respiratory tract.…”

Section: Organ Tropism and Neuroinfective Routessupporting

confidence: 73%

“…Rhesus macaques infected with bronchoalveolar lavage fluid obtained from an affected patient developed a histopathologically confirmed interstitial pneumonia, associated with a widespread presence of SARS-CoV-2 in the respiratory tract. Clinical signs were mild and no viral RNA was detectable by means of RT-qPCR in the blood of the primates during the whole course of infection (14 days) [44]. These findings demonstrate the causal relationship between SARS-Cov-2 and interstitial pneumonia, reminiscent of COVID-19.…”

Section: Organ Tropism and Neuroinfective Routesmentioning

confidence: 73%

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Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

Natoli

Oliveira

Calabresi

et al. 2020

Euro J of Neurology

238

242

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The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.

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Section: Organ Tropism and Neuroinfective Routessupporting

confidence: 73%

Section: Organ Tropism and Neuroinfective Routesmentioning

confidence: 73%

Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

Natoli

Oliveira

Calabresi

et al. 2020

Euro J of Neurology

238

242

View full text Add to dashboard Cite

show abstract

“…Although the retrospective studies of COVID-19 have given us some answers 23 , further investigation also needs to be performed in various animals. So far, several animal models of COVID-19 have been reported to successfully recapitulate some aspects of this disease [5][6][7][8][9][10][11] and also indicate that these experimental animals are susceptible to SARS-CoV-2 infection.…”

Section: Histopathological Characteristics In Sars-cov-2 Infected Trementioning

confidence: 98%

“…From these points of view, studies of animals become essentially important. In fact, several animal models of COVID-19 have been recently reported in murine 5 , hamster 6 , ferret 7 , and non-human primate [8][9][10][11] , which recapitulate COVID-19 from different aspects. In terms of susceptibility to SARS-CoV-2, in addition to these experimental animals, domestic animals and pets are also investigated 12 .…”

mentioning

confidence: 99%

Susceptibility of tree shrew to SARS-CoV-2 infection

Zhao

Wang

Kuang

et al. 2020

Preprint

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Since SARS-CoV-2 became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health.Many scientific questions about SARS-CoV-2 and COVID-19 were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39 ) particular in female animals during infection. Low levels of virus shedding and replication in tissues occurred in all three age groups, each of which showed his own characteristics. Histopathological examine revealed that pulmonary abnormalities were mild but the main changes although slight lesions were also observed in other tissues. In summary, tree shrew is not susceptible to SARS-CoV-2 infection and may not be a suitable animal for COVID-19 related researches.

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“…and that both viruses may have an extended host range that includes primates and other mammals (1)(2)(3) . However, the immediate source population/species for SARS-CoV and SARS-CoV-2 viruses has not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

Damas¹,

Hughes

Keough³

et al. 2020

Preprint

162

241

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The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low . Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

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Infection with Novel Coronavirus (SARS-CoV-2) Causes Pneumonia in the Rhesus Macaques

Cited by 81 publications

References 0 publications

Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

Susceptibility of tree shrew to SARS-CoV-2 infection

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

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