Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression

Abstract

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5–7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1β), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1β/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

Development of a coronavirus disease 2019 nonhuman primate model using airborne exposure

“…By Study Day 18, most clinical disease signs (including radiographic findings) had either completely resolved or were resolving, and virus in lung tissue was below the limit of detection by ISH. Prior studies have demonstrated the ability to consistently detect SARS-CoV-2 virus by immunohistochemistry of ISH in formalin-fixed tissues collected prior to Study Day 10 [ 25 – 27 ]. However, similar to the data described herein, assessment of tissues by these methods after Study Day 10 typically leads to negative results.…”

The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18–59 years: A phase I randomized, double-blinded, controlled trial

“…Before this vaccine was released for clinical study by the CFDA under No. 2020L00020, the protective efficacy of the vaccine was tested in the macaque challenge test [11] , [12] , and various toxicity studies, including an acute toxicity test, a long-term toxicity test and an allergic test, demonstrated its safety in nonhuman primates and rodents. The placebo contained only the same amount of Al(OH) 3 in buffer.…”

Animal models for SARS-CoV-2

“…The administration of neutralizing antibodies targeting spike protein was prophylactically and therapeutically effective in NHP models [ 69 , 90 ]. NHP models have an important advantage in preclinical studies in that immune responses following SARS-CoV-2 infection recapitulate crucial aspects of COVID-19 in humans [ 91 , 92 ]. For this reason, researchers evaluating different vaccine platforms including adenovirus vectored [ 46 , 93 , 94 ], DNA [ 95 ], mRNA [ 96 ], inactivated [ 44 ], and subunit vaccines [ 97 ] have applied NHP models for assessing the immunogenicity and protective efficacy.…”