Abstract
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.
Highlights
Emiko Uranoa, Tomotaka Okamuraa, Chikako Onob, Shiori Uenoc, Satoshi Nagatad, Haruhiko Kamadae, Mahoko Higuchia, Mugi Furukawaa, Wataru Kamitanic, Yoshiharu Matsuurab, Yoshihiro Kawaokaf,g,h, and Yasuhiro Yasutomia,i,1
Obvious clinical symptoms were not observed in young Cynomolgus monkeys (CMs), but scores for clinical signs in addition to age-related factors increased in the elderly group after SARS-CoV-2 infection (Fig. 1A)
Considering the physical burden for elderly CMs, body temperature was monitored daily by an intraperitoneally embedded data logger in only four young CMs, and all of those four CMs had a fever at day 1 postinfection (p.i.)
Summary
Emiko Uranoa , Tomotaka Okamuraa, Chikako Onob, Shiori Uenoc, Satoshi Nagatad , Haruhiko Kamadae , Mahoko Higuchia, Mugi Furukawaa, Wataru Kamitanic, Yoshiharu Matsuurab , Yoshihiro Kawaokaf,g,h, and Yasuhiro Yasutomia,i,1. COVID-19 cynomolgus monkey models including monkeys with underlying diseases causing severe pathogenicity such as metabolic disease and elderly monkeys were examined. 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. A detailed understanding of pathological conditions and development of effective therapeutic agents are needed to overcome the pandemic of diseases caused by SARS-CoV-2 infection, which has been named COVID-19. COVID-19 model CMs, including healthy young CMs, elderly CMs (23 to 30 y of age, equivalent to 69 to 90 y of age in humans), and CMs with underlying diseases including diabetes and hyperlipidemia were experimentally infected with SARS-CoV-2 as animal models reflecting human pathology
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