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. 2020 Aug;30(8):670-677.
doi: 10.1038/s41422-020-0364-z. Epub 2020 Jul 7.

Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques

Chao Shan #  1   2 , Yan-Feng Yao #  3 , Xing-Lou Yang #  3 , Yi-Wu Zhou #  4 , Ge Gao  3 , Yun Peng  3 , Lian Yang  5 , Xue Hu  3   6 , Jin Xiong  3 , Ren-Di Jiang  3   7 , Hua-Jun Zhang  3 , Xiao-Xiao Gao  3 , Cheng Peng  3 , Juan Min  3 , Ying Chen  3   7 , Hao-Rui Si  3 , Jia Wu  3 , Peng Zhou  3 , Yan-Yi Wang  3 , Hong-Ping Wei  3 , Wei Pang  8 , Zheng-Fei Hu  9 , Long-Bao Lv  9 , Yong-Tang Zheng  8 , Zheng-Li Shi  10 , Zhi-Ming Yuan  11
Affiliations

Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques

Chao Shan et al. Cell Res. 2020 Aug.

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Experimental scheme, body weight change, body temperature change and viral RNA load dynamics in SARS-CoV-2-infected RMs.
a Experimental scheme and experimental parameters. Six RMs were intratracheally inoculated with 7 × 106 TCID50 of SARS-CoV-2. Mock 1 and Mock 2 were two control animals treated with DMEM. Disease parameters were measured including changes of body weight, body temperature and behaviors at the indicated time points. Viral loads in blood and swabs were monitored to evaluate viral replication kinetics in RMs. Blood and swab sample collection, chest X-ray examination and necropsy with organ pathological examination were performed at the indicated time points. The viral RNA was extracted by Qiagen Viral RNA kit, followed by RT-qPCR to quantify viral RNA. b Body weight changes of RMs after infection with SARS-CoV-2. c Changes of rectal temperature of RMs after infection with SARS-CoV-2. d Viral RNA load in blood. e Viral RNA load in oropharyngeal swabs. f Viral RNA load in nose. g Viral RNA load in rectal tract. L.O.D. limit of detection, 200 copies/mL.
Fig. 2
Fig. 2. Characterization of the respiratory tract changes after SARS-CoV-2 infection.
a Radiographs of the chest of RM before inoculation and on day 3 and day 6 post infection with SARS-CoV-2. The red circled areas are regions of interstitial infiltrates indicative of viral pneumonia. b, c Lesions in the lungs. A view of the ventral lungs of an infected animal obtained at necropsy on day 3 and 6 post infection, showing severe hemorrhage and necrosis of lung (white circles). Scale bar, 5 mm. Viral loads in trachea, bronchus, right and left upper, middle, and lower lung lobes on day 3 (d) and day 6 (e). Red bar, RM2; black bar, RM6; pink bar, RM3; orange bar, RM5. Error bars mean standard deviation from two technical repeats. L.O.D. limit of detection, 103–104 copies/g as the tissue weight varies.
Fig. 3
Fig. 3. Histopathological analysis of lung changes in RMs infected with SARS-CoV-2.
Six RMs were inoculated with SARS-CoV-2. Two animals were euthanized at 3 days post infection, and 2 animals at 6 days post infection. Histological analysis was performed on tissues collected at 3 and 6 days post infection. a HE staining of the lung tissues. b Masson staining of lung tissue. c Immunofluorescence analysis of SARS-CoV-2 in lung tissue. A rabbit polyclonal antibody raised against the SARS-CoV NP protein was used for specific staining of SARS-CoV-2 antigen. Black scale bar, 500 µm; blue scale bar, 50 µm; white scale bar, 50 µm. Blue triangle, pulmonary fibrosis; black triangle, macrophages; yellow triangle, edema; green triangle, pulmonary hyaline membrane formation; pink triangle, neutrophil.
Fig. 4
Fig. 4. Challenge on the infected RMs.
a Experimental scheme and experimental parameters. Two pre-infected and two control (C1 and C2) RMs were intratracheally inoculated with 1 × 106 TCID50 of SARS-CoV-2. Disease parameters were measured including changes of body weight, body temperature and behaviors at the indicated time points. Viral loads in blood and swabs were monitored to evaluate viral replication kinetics in RMs. Body weight (b) and body temperature (c) were monitored at the indicated time points. d Viral load from oropharyngeal swabs were monitored by qRT-PCR. L.O.D. limit of detection, 200 copies/mL.
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References

    1. WHO. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV) (2020).
    1. Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. WHO. Coronavirus disease 2019 (COVID-19) Situation Report—119 (2020).
    1. Xu Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020;8:420–422. doi: 10.1016/S2213-2600(20)30076-X. - DOI - PMC - PubMed
    1. Guan WJ, et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032. - DOI - PMC - PubMed

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