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Comparison of SARS-CoV-2 Infections Among Three Species of Non-Human Primates
27 Pages Posted: 8 May 2020More...
Background: COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Remarkable achievements have been made in diagnosis, prevention and treatment of COVID-19 from clinical studies. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines.
Methods: Two families of three species of non-human primates (NHP), old world monkeys (Macaca mulatta, Macaca fascicularis) and new world monkeys (Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and evaluation of host responses to SARS-CoV-2 infection.
Findings: Increased body temperature was observed in M. mulatta and M. fascicularis, but not C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in swab samples and blood from all 3 species of monkeys. Viral shedding from upper respiratory reached the peak between day 6 and day 8 post inoculation. Viruses were mainly detected in lung, weasand, bronchus and spleen of M. mulatta and M. fascicularis, but not C. jacchus. M. mulatta showed stronger cytokine responses to SARS-CoV-2 infection than M. fascicularis. Severe gross lesions and histopathological changes were observed mainly in lung and secondary lymphoid of SARS-CoV-2 infected M. mulatta and M. fascicularis. The susceptibility to SARS-CoV2 infection is M. mulatta > M. fascicularis > C. jacchus.
Interpretations: We have established a NHP model for COVID-19, which recapitulates several important aspects of COVID-19 patients and could be used to evaluate anti-viral drugs and vaccines, and investigate viral pathogenesis.
Funding Statement: This study was supported by 2020YFC0841100 and 2020YFC0846400.
Declaration of Interests: None.
Ethics Approval Statement: All animal procedures were approved by the Institutional Animal Care and Use Committee of Institute of Medical Biology, Chinese Academy of Medical Science (Ethics number: DWSP202002 001), and performed in the ABSL-4 facility of National Kunming High-level Biosafety Primate Research Center, Yunnan China.
Keywords: SARS-CoV-2; COVID-19; non-human primate; animal model; inflammatory cytokines
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