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

PLoS Pathog. 2020 Nov 12;16(11):e1008949. doi: 10.1371/journal.ppat.1008949. eCollection 2020 Nov.

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.

MeSH terms

  • Animals
  • Betacoronavirus / pathogenicity*
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Cytokines / immunology
  • Disease Models, Animal
  • Lung / immunology
  • Lung / pathology
  • Macaca mulatta
  • Pandemics
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Viral Load / methods
  • Virulence
  • Virus Shedding

Substances

  • Cytokines

Grants and funding

The author(s) received no specific funding for this work.