Abstract
Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease 2019 (COVID-19), which poses an unprecedented worldwide health crisis, and has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The angiotensin converting enzyme 2 (ACE2) has been suggested to be the key protein used by SARS-CoV-2 for host cell entry. In their recent work, Lindskog and colleagues (Hikmet etal, 2020) report that ACE2 is expressed at very low protein levels-if at all-in respiratory epithelial cells. Severe COVID-19, however, is characterized by acute respiratory distress syndrome and extensive damage to the alveoli in the lung parenchyma. Then, what is the role of the airway epithelium in the early stages of COVID-19, and which cells need to be studied to characterize the biological mechanisms responsible for the progression to severe disease after initial infection by the novel coronavirus?
Highlights
To elucidate the pathogenesis of COVID-19, it is of critical importance to identify the cells infected by SARS-CoV-2, as well as the mechanisms of viral entry, replication, and the ensuing cellular damage leading to the induction of innate and adaptive antiviral responses
The authors show that angiotensin converting enzyme 2 (ACE2) expression in the respiratory tract is very limited compared to other barrier tissues, and reproducible staining is observed in nasal epithelial cells with only one of the two antibodies used in this study, prompting the authors to claim that none or only very low levels of ACE2 protein is present in the normal respiratory system
Identification of the entry site of SARSCoV-2 in COVID-19 patients will facilitate focused research efforts to test whether and how the early response to viral infection governs progression to severe and fatal disease. Such insight into the pathogenesis of early stages of COVID-19 might aid the identification of biomarkers for those patients most likely to progress to severe disease, and guide design of therapeutic interventions aiming at preventing severe disease in its variations
Summary
Can ACE2 expression explain SARS-CoV-2 infection of the respiratory epithelia in COVID19? Nawijn, Martijn C; Timens, Wim. Several recent studies report on the expression of ACE2 mRNA in tissues or individual cells, identifying the upper airway epithelium as the most likely site of entry for SARS-CoV-2 (Lukassen et al, 2020; Sungnak et al, 2020). In their recent study, Hikmet et al (2020) present a muchneeded updated systematic evaluation of ACE2 expression in a large range of tissues, at the protein as well as the RNA level, confirming the expression in a number of epithelial barrier tissues. In the normal respiratory system, the authors observe positive staining only with one of two antibodies used, in ciliated cells in the nasal cavity (in all subjects tested), in the bronchus (in a subset of the subjects tested), and in a subset of alveolar type-2 epithelial cells, and conclude that ACE2 protein expression in lung is very limited at best
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