ABSTRACT
Objective To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. Methods The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. Results The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. Conclusions At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.
ABSTRACT
Objectives: To analyze follow-up CTs of patients recovering from COVID-19 in Wuhan, focusing on fibrotic change and its relevant risk factors. Methods: From January 13 to February 27, 2020, 166 hospitalized patients meeting our criteria were included. The scores of fibrotic patterns on follow-up CT were evaluated. Patients were designated as group 1 (with CT evidence of fibrotic pattern) and group 2 (without CT evidence of fibrotic pattern). Multivariate logistic regression was performed to explore risk factors for fibrotic change in patients with COVID-19. Results: The follow-up CTs were obtained on 56 days (median, IQR 51-63 days) after symptom onset. Of the 166 patients (mean age, 57 ± 15 years; 69/166 male), 46% (76/166) had CT evidence of fibrotic change and 77% (127/166) were severe or critical cases. Among patients with fibrotic change on CT, 84% (64/76) got a minimal or mild score of fibrosis. The high total score on peak CT, peak eosinophils, erythrocyte sedimentation rate (ESR) and advancing age were related to lung fibrotic change in patients with COVID-19. Conclusion: Forty six percentages of patients (mainly severe or critical cases) with COVID-19 showed fibrotic change on follow-up CT at early recovery phase, while the extent of fibrosis was not large. The advancing age, high total score on peak CT, peak eosinophils and ESR were associated with fibrotic change depicted by CT in patients recovering from COVID-19. An extended follow up by CT imaging and pulmonary function testing is necessary to fully assess the sequela of COVID-19.