期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：43
DOI：10.1073/pnas.2104847118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
COVID-19 has shown severe pathogenicity in people with underlying diseases and in elderly people. It is necessary to elucidate the pathological conditions in patients with underlying diseases and in elderly patients. The use of appropriate animal models of COVID-19 is required for the development of pharmaceutical products; however, usually healthy young animals are used as experimental animals. Cynomolgus macaques with various clinical conditions and ages were infected with severe acute respiratory syndrome coronavirus 2 and there was a difference in pathological condition between young individuals and old-aged individuals with underlying diseases; therefore, the COVID-19 cynomolgus monkey model reflecting the pathophysiology of humans would be useful for elucidating the pathophysiology and developing therapeutic and prophylactic agents.
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and life. A useful pathological animal model accurately reflecting human pathology is needed to overcome the COVID-19 crisis. In the present study, COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. Cynomolgus macaques with various clinical conditions were intranasally and/or intratracheally inoculated with SARS-CoV-2. Infection with SARS-CoV-2 was found in mucosal swab samples, and a higher level and longer period of viral RNA was detected in elderly monkeys than in young monkeys. Pneumonia was confirmed in all of the monkeys by computed tomography images. When monkeys were readministrated SARS-CoV-2 at 56 d or later after initial infection all of the animals showed inflammatory responses without virus detection in swab samples. Surprisingly, in elderly monkeys reinfection showed transient severe pneumonia with increased levels of various serum cytokines and chemokines compared with those in primary infection. The results of this study indicated that the COVID-19 cynomolgus monkey model reflects the pathophysiology of humans and would be useful for elucidating the pathophysiology and developing therapeutic agents and vaccines.
