Abstract

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.

Highlights

  • Coronavirus infections are common in humans and other mammals.Coronaviruses belong to the family Coronaviridae and possess a single-stranded, positive-sense RNA genome ranging from 26 to 32 kilobases in length

  • The histopathological changes of heart, liver, kidney, spleen, stomach, ileum, colon and testis were shown in Supplementary information, Fig. S6. Those organs showed varying levels of edema, increase or infiltration of inflammatory cells on day 3 post infection, while the symptom was relieved slightly on day 6 post infection. These results suggested that SARS-CoV-2 could infect the respiratory tract resulting in interstitial pneumonia in Rhesus macaques (RMs)

  • Since the outbreak, establishing the animal model for SARS-CoV-2 to assess the efficacy of medical countermeasures has been ongoing

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Summary

Introduction

Coronavirus infections are common in humans and other mammals.Coronaviruses belong to the family Coronaviridae and possess a single-stranded, positive-sense RNA genome ranging from 26 to 32 kilobases in length. Coronavirus infections are common in humans and other mammals. In December 2019, a cluster of cases of pneumonia were reported in people associated with the Huanan. (SARS-CoV-2) and considered as the pathogen of the current outbreak of coronavirus disease (COVID-19).[1] The common clinical features for COVID-19 include fever, cough, myalgia, fatigue, dyspnea, lymphopenia, and pneumonia; less common symptoms include sputum production, headache, haemoptysis, and diarrhea.[2]. As of May 26, 2020, a total of 5,370,375 cases had been reported in 216 countries, areas or territories with more than 344,454 deaths,[3] whereas a sizable portion of infected but non-symptomatic people with potential of transmissibility was reported.[4,5] Due to the urgency of the situation, World Health Organization declared COVID-

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