Therefore, the effect of aging around the inflammatory responses in the lungs may be minor during the early stage of infection, although acquired immune responses, such as the induction of neutralizing antibodies, may have been influenced by the age as reported in monkey models [11]

Therefore, the effect of aging around the inflammatory responses in the lungs may be minor during the early stage of infection, although acquired immune responses, such as the induction of neutralizing antibodies, may have been influenced by the age as reported in monkey models [11]. Although there was no apparent effect of age on body weight loss after infection as well as virus titers and inflammatory responses in the lungs, prolongation of PT was observed only in the aged hamsters in this study. lungs, suggesting that consumption of coagulation factors causes prothrombin time prolongation. Furthermore, proximal urinary tract damage and mesangial matrix growth were observed in the kidneys of the aged hamsters at early and later disease stages, respectively. Given that the severity and mortality of COVID-19 are higher in elderly human patients, the effect of aging on pathogenesis needs to be understood and should be considered for the selection of animal models. We, thus, propose that the aged hamster is a good small animal model for COVID-19 research. 0.01, two-way analysis of variance Rabbit polyclonal to TP73 (ANOVA)], as shown in Physique 1a. At 6 dpi, the average body weight was 87.2% 0.6% in young and 87.8% 0.6% in aged hamsters. No significant difference in body weight change was observed between young Lu AE58054 (Idalopirdine) and aged hamsters at all the time points. At 6 dpi, the hamsters were sacrificed, and blood, serum, lung, liver, and kidney samples were collected to evaluate the effect of SARS-CoV-2 contamination on the blood parameters and other tissues. Open in a separate window Physique 1 Changes of body weight and blood parameters in young and aged hamsters infected with SARS-CoV-2. Young (9 w) and aged ( 36 w) hamsters were intranasally inoculated with PBS control (mock) or PBS containing SARS-CoV-2 computer virus (CoV2). Body weight was monitored daily until 6 days post contamination (dpi) (a), and the hamsters were euthanized at 6 dpi for the collection of blood samples for measurement of acid-base status parameters BEecf and HCO3? (b), and prothrombin time (c). (a) Symbols indicate the mean body weight SEM represented as a percentage of the original weight [mock (9 w), = 7; CoV2 (9 w), = 12; mock ( 36 w), = 7; CoV2 ( 36 w), = 17]. Circles and triangles indicate data from young and aged hamsters, respectively. Open and closed symbols indicate PBS control and virus-infected hamsters, respectively. ### 0.001, #### 0.0001 (young); ** 0.01, *** 0.001, **** 0.0001 (aged); two-way ANOVA with Tukeys multiple comparison test. No significant difference was detected between young and aged hamsters at each time point. (b,c) White and gray bars indicate data from mock and CoV2-infected hamsters, respectively. Each dot indicates data from each individual. Bars indicate the mean SEM Lu AE58054 (Idalopirdine) [(b) mock (9 w), = 8; CoV2 (9 w), = 6; mock ( 36 w), = 9; CoV2 ( 36 w), = 10] or the median interquartile; (c) 9 w-mock, = 6; 9 w-CoV2, = 12; 36 w-mock, = 7; 36 w-CoV2, = 16]. * 0.05, *** 0.001, **** 0.0001, two-way ANOVA with Sidaks multiple comparison test. BEecf, base extra extracellular fluid; PT-INR, international normalized ratio of prothrombin time; NS, non-significant. An imbalanced acidCbase status was suggested in infected hamsters regardless of age at 6 dpi (Physique 1b). In both young and aged hamsters, base extra extracellular fluid (BEecf) and HCO3? levels, known as metabolic alkalosis indicators, were elevated after computer virus contamination ( 0.0005, two-way ANOVA). With respect to computer virus infection-induced pneumonia, elevated BEecf and HCO3? may have resulted from renal compensation for respiratory acidosis in the infected hamsters. Since coagulopathy has been reported in human patients with severe COVID-19 [2,3], the international normalized ratio of PT (PT-INR), a clinical index of the duration of blood coagulation, was evaluated. Interestingly, the median values of PT-INR of the aged hamsters were 1 in mock and 1.25 in infected animals, and a significant difference was observed despite the large individual variance ( 0.05, Lu AE58054 (Idalopirdine) Lu AE58054 (Idalopirdine) two-way ANOVA; Physique.