ACE2 Expression is elevated in Airway Epithelial Cells from aged and male donors but reduced in asthma (preprint)

Rationale: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter airway epithelial cells (AECs). Objective: To determine what factors are associated with ACE2 expression particularly in patients with asthma and chronic obstructive pulmonary disease (COPD). Methods: We obtained upper and lower AECs from 145 people from two independent cohorts, aged 2-89, Newcastle (n=115), and from Perth (n= 30) Australia. The Newcastle cohort was enriched with people with asthma (n=37) and COPD (n=38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry were assessed by quantitative PCR, protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AECs. Results: Increased gene expression of ACE2 was associated with older age (p=0.02) and male sex (p=0.03), but not pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma (p=0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in asthma (p=0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface was increased (p=0.02). ACE2 protein levels were lower in endobronchial biopsies from asthma patients. Conclusions: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.

Dynamic Changes of Chest CT Follow-up In Coronavirus Disease-19 (COVID-19) Pneumonia: Relationship To Clinical Typing (preprint)

Background: To investigate the CT changes of different clinical types of COVID-19 pneumonia. Methods: : This retrospective study included 50 patients with COVID-19 from 16 January 2020 to 25 February 2020. We analyzed the clinical characteristics, CT characteristics and the pneumonia involvement of the patients between the moderate group and the severe and critical group, and the dynamic changes of severity with the CT follow-up time. Results: : There were differences in the CT severity score of the right lung in the initial CT, and total CT severity score in the initial and follow-up CT between the moderate group and the severe and critical group (all p <0.05). There was a quadratic relationship between total CT severity score and CT follow-up time in the severe and critical group (r 2 =0.137, p=0.008), the total CT severity score peaked at the second follow-up CT. There was no correlation between total CT severity score and CT follow-up time in the moderate group (p >0.05). There were no differences in the occurrence rate of CT characteristics in the initial CT between the two groups (all p >0.05). There were differences in the occurrence rate of ground-glass opacity and crazy-paving pattern in the second follow-up CT, and pleural thickening or adhesion in the third follow-up CT between the two groups (all p <0.05). Conclusions: : The CT changes of COVID-19 pneumonia with different severity were different, and the extent of pneumonia involvement by CT can help to assess the severity of COVID-19 pneumonia rather than the initial CT characteristics.

Dynamic Changes of Chest CT Follow-up In Coronavirus Disease-19 (COVID-19) Pneumonia: Relationship To Clinical Typing (preprint)

ObjectivesTo investigate the  CT changes of  different clinical  types  of  COVID-19 pneumonia.MethodsThis retrospective study included 50 confirmed patients with COVID-19 from 16 January 2020 to 25 February 2020. We analyzed the clinical and CT characteristics of the patients between the moderate group and the severe and critical group, and the dynamic changes of severity with the CT follow-up time.ResultsThere were no differences in the occurrence rate of CT characteristics between the moderate group (n=34) and the severe and critical group (n=16) in the initial CT (all p >0.05). There were differences in the CT score of right lung and total CT score at the initial CT between the two groups (all p <0.05). There was a quadratic relationship between total CT score and CT follow-up time in the severe and critical group (r2=0.137, p=0.008), the total CT severity score peaked at the second follow-up CT. There was no correlation between total CT score and CT follow-up time in the moderate group (p >0.05). The total CT score of the severe and critical group was different between the initial and first follow-up, the second and third follow-ups, the third and fourth follow-ups, and the fourth and fifth follow-ups CT (all p<0.05). The total CT score of the moderate group was different between the second and third follow-ups CT (p<0.05).ConclusionsCOVID-19 pneumonia with the severe and critical types progressed rapidly with the greatest severity at the second follow-up CT, and the moderate type was relatively stable.