Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Harlan Barker; Seppo Parkkila

The predominant pathological features of COVID-19 infection largely mimic those previously reported for SARS-CoV-1 infection. They include dry cough, persistent fever, progressive dyspnea, and in some cases acute exacerbation of lung function with bilateral pneumonia (30). Major lung lesions include several pathological signs, such as diffuse alveolar damage, inflammatory exudation in the alveoli and interstitial tissue, hyperplasia of fibrous tissue, and eventually lung fibrosis (43) (44) (45) . It has been shown by fluorescence in situ hybridization technique that SARS-CoV-1 RNA locates to the alveolar pneumocytes and alveolar space (46, 47) . Considering all these facts, it is not surprising that most histopathological analyses have been focused on distal parts of the respiratory airways, while the regions other than the alveolus have been less systematically studied. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038752 doi: bioRxiv preprint intermediate cells between goblet, ciliated, and club cells. If SARS-coronaviruses predominantly attack these cells, locating along the airway segments including the trachea, bronchi, and bronchioles until the last segment that is the respiratory bronchioles, it would be obvious that physiological protective mechanisms are severely affected. Defective mucosal protection and inefficient removal of pathogens due to viral infection may contribute to onset of severe bilateral pneumonia that is common for SARS-diseases (51) . This pathogenic mechanism is supported by previous findings, showing that early disease is manifested as a bronchiolar disease with respiratory epithelial cell necrosis, loss of cilia, squamous cell metaplasia, and intrabronchiolar fibrin deposits When we initiated the present study, we hypothesized that understanding better the transcriptional regulation of the ACE2 gene might help to explain the peculiar distribution pattern of ACE2 in tissues. Since upregulation of ACE2 would reflect an increased number of SARS-coronavirus receptors on cell surfaces, it could possibly help us to understand the mechanisms why certain patients (males more than females, old more than young, smokers more than non-smokers) are more susceptible for the most detrimental effects of the COVID-19 infection. In our study, the signals for ACE2 mRNA in the lung specimens did not vary much in different age groups nor did they show significant differences between males and females, which is in line with the previous findings (48) .