Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques
Chao Shan1,2, Yan-Feng Yao3, Xing-Lou Yang3
1Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China. shanchao@wh.iov.cn.
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.
Insights
Rhesus macaques are susceptible to SARS-CoV-2 infection, developing interstitial pneumonia. Neutralizing antibodies from primary infection protected against re-challenge, establishing a valuable model for studying the virus and testing interventions.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- The 2019 novel coronavirus (SARS-CoV-2) outbreak poses a significant global public health challenge.
- Understanding the dynamics of SARS-CoV-2 infection, replication, and shedding is crucial but poorly understood.
- A suitable animal model is needed to study pathogenesis and evaluate potential vaccines and therapeutics.
Purpose of the Study:
- To investigate the susceptibility of Rhesus macaques to SARS-CoV-2 infection.
- To characterize the viral dynamics, pathological changes, and immune response in infected Rhesus macaques.
- To establish a non-human primate model for SARS-CoV-2 research.
Main Methods:
- Intratracheal inoculation of Rhesus macaques with SARS-CoV-2.
- Monitoring viral RNA levels in oropharyngeal swabs and respiratory tract tissues.
- Histopathological examination of lung tissues.
- Re-isolation of infectious virus from swabs and tissues.
- Assessing protection against secondary SARS-CoV-2 challenge following primary infection.
Main Results:
- Rhesus macaques were susceptible to SARS-CoV-2 infection, with viral RNA peaking at 1 and 5 days post-infection.
- Infection led to interstitial pneumonia characterized by hyperemia, edema, and inflammatory cell infiltration.
- SARS-CoV-2 RNA was detected in multiple respiratory tract tissues, and infectious virus was re-isolated.
- Neutralizing antibodies generated after primary infection conferred protection against a second SARS-CoV-2 challenge.
Conclusions:
- Rhesus macaques serve as a susceptible model for SARS-CoV-2 infection, mimicking key aspects of human disease.
- The established non-human primate model is valuable for studying SARS-CoV-2 pathogenesis.
- This model provides a platform for evaluating the efficacy of candidate vaccines and therapeutics against SARS-CoV-2.
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