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

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.

NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

“…Lung tissues were collected from all animals at 7 days post challenge and sections examined for pathologic changes within the upper and lower airways. Consistent with Rev08 10 previous reports of SARS-CoV-2 infection in rhesus macaques [5][6][7][8][9][10] placebo control animals had moderate to severe inflammation that involved the mucosa of the bronchi, perivascular mononuclear infiltrate with mixed infiltrates of macrophages and neutrophils within the alveoli. In contrast, there was little, or no inflammation observed in the lungs of macaques immunized with NVX-CoV2373 vaccine 7 days post challenge (Figure 2).…”

Structural and functional modelling of SARS-CoV-2 entry in animal models

“…Further validation of our approach comes from the RBD-macACE2 complex (Supplementary Figure S3). The level of sequence identity between hACE and macACE2 is 95.6% (Supplemental Figure S2) and our modelling show that the RBD-hACE2 and RBD macACE2 complexes are overall very similar, in line with experimental data showing that SARS-CoV-2 replication and shedding and disease symptoms are similar in human and macaque 42,43 .…”

SARS-CoV-2 vaccines in development

“…Several animal models for SARS-CoV-2 have been developed including mice expressing human ACE2, either via adenovirus transduction or by genetic engineering 61,62 , mouse models with mouse adapted SARS-CoV-2 strains [63][64][65][66][67] , ferrets [68][69][70] as well as hamsters [71][72][73] and nonhuman primates (especially rhesus macaques) 23,33,[74][75][76][77][78][79][80][81] . The hamster model can mimic severe disease as seen in a proportion of humans while the NHP model more reflects mild to moderate infection.…”