부산대학교 도서관

The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe disease, diminishing their utility for research focusing on severe disease pathogenesis and life-saving medical countermeasures. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species of nonhuman primates (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM). Species-specific cohorts were experimentally infected with SARS-CoV-2 by either direct mucosal (intratracheal + intranasal) instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated analogous viral loads in all compartments by either exposure route although the magnitude and duration of viral loading was marginally greater in AGMs than RMs. Clinical onset was nearly immediate (+1dpi) in the mucosal exposure cohort whereas clinical signs and cytokine responses in aerosol exposure animals began +7dpi. Pathologies conserved in both species and both exposure modalities include pulmonary myeloid cell influx, development of pleuritis, and extended lack of regenerative capacity in the pulmonary compartment. Demonstration of conserved pulmonary pathology regardless of species and exposure route expands our understanding of how SARS-CoV-2 infection may lead to ARDS and/or functional lung damage and demonstrates the near clinical response of the nonhuman primate model for anti-fibrotic therapeutic evaluation studies. Author summary: The advent of COVID-19's quick emergence as a human disease necessitated near immediate development of animal models that would recapitulate the viral syndrome to facilitate study of spread, health effects, and evaluation of medications that could either treat or prevent disease. In this study, we compared the health effects of viral infection in two species of nonhuman primates, using two distinct routes of infection which were aerosol or instillation into the nose and upper lung. The results showed that although not effecting overall response in either species of animal, the route by which the experimental infection was performed effected the movement of infectious virus in the animal's body once infected. These results have implications of what is known about the potential route of transmission of this emerging viral disease. [ABSTRACT FROM AUTHOR]