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. 2020 Mar 30;3(1):93-97.
doi: 10.1002/ame2.12108. eCollection 2020 Mar.

Age-related rhesus macaque models of COVID-19

Pin Yu  1 , Feifei Qi  1 , Yanfeng Xu  1 , Fengdi Li  1 , Peipei Liu  2 , Jiayi Liu  3 , Linlin Bao  1 , Wei Deng  1 , Hong Gao  1 , Zhiguang Xiang  1 , Chong Xiao  1 , Qi Lv  1 , Shuran Gong  1 , Jiangning Liu  1 , Zhiqi Song  1 , Yajin Qu  1 , Jing Xue  1 , Qiang Wei  1 , Mingya Liu  1 , Guanpeng Wang  1 , Shunyi Wang  1 , Haisheng Yu  1 , Xing Liu  1 , Baoying Huang  2 , Wenling Wang  2 , Li Zhao  2 , Huijuan Wang  2 , Fei Ye  2 , Weimin Zhou  2 , Wei Zhen  2 , Jun Han  2 , Guizhen Wu  2 , Qi Jin  4 , Jianwei Wang  5 , Wenjie Tan  2 , Chuan Qin  1
Affiliations

Age-related rhesus macaque models of COVID-19

Pin Yu et al. Animal Model Exp Med. .

Abstract

Background: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.

Methods: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response.

Results: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages.

Conclusion: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

Keywords: SARS‐CoV‐2; pathogenicity; pneumonia; rhesus macaque model.

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Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
Viral load of the SARS‐CoV‐2‐infected rhesus macaque model. A. Average viral loads of swabs from the younger group (YG, n  = 3, red line) monkeys. B. Average viral load of swabs from the elder group (EG, n  = 2, blue line) monkeys. Viral loads of nasal, throat, and anal swab specimens collected from the inoculated macaques on 0, 3, 5, 7, 9, 11, and 14 dpi. C. Viral loads in varies lobe of lung tissue from YG and EG monkeys at day 7 post‐inoculation. RNA was extracted and viral load was determined by qRT‐PCR. All data are presented as mean ± SEM
FIGURE 2
FIGURE 2
The comparison of lesions in the lung between younger group (YG) and elder group (EG) by radiographic alterations, histopathological and immunohistochemical (IHC) observation of the SARS‐CoV‐2‐inoculated‐rhesus macaque. A. Anterior‐posterior thoracic X‐rays from of rhesus macaque imaged prior to SARS‐CoV‐2 inoculation (day 0) and on 7 dpi of YG and 5 dpi of EG. Areas of interstitial infiltration, indicative of pneumonia, are highlighted (red circle). Positional indicators are included (R = right). B. Histopathological changes in lungs from YG and EG. Lung tissue was collected and stained with hematoxylin and eosin. Black scale bar = 40 µm. IHC staining demonstrated that SARS‐CoV‐2 antigens were mainly in the epithelial cells and macrophages. SARS‐CoV‐2 antigens were indicated by red arrows. Red scale bar = 50 µm
FIGURE 3
FIGURE 3
Hematological analysis in rhesus macaques inoculated with SARS‐CoV‐2. A. The counts of white blood cells (WBC) were analysed. B. The percentage and counts of monocytes were determined. C. The percentage and counts of lymphocytes were detected. D. The percentage and counts of CD3+ CD8+ T cells, CD3+ CD4+ T cells were shown. YG (red line) and EG (blue line) were indicated in the upper right corner of each panel. All data are presented as mean ± SEM
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References

    1. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727‐733. - PMC - PubMed
    1. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus‐infected pneumonia. N Engl J Med. 2020. - PMC - PubMed
    1. WHO . Coronavirus disease 2019 (COVID‐19) Situation Report, 2020; https://www.who.int/docs/default-source/coronaviruse/situation-reports/2...
    1. Yang Y, Lu Q, Liu M, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv . 2020. 10.1101/2020.02.10.20021675 - DOI
    1. Letko M, Munster V. Functional assessment of cell entry and receptor usage for lineage B β‐coronaviruses, including 2019‐nCoV. bioRxiv. 2020. 10.1101/2020.01.22.915660 - DOI - PMC - PubMed