The following is a summary of “Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages” published in the December 2022 issue of Respiratory by Hönzke et al.


The transmembrane peptidase angiotensin-converting enzyme 2 (ACE2) is used by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an entrance receptor into cells. It is unclear, however, whether SARS-CoV-2 in the alveolar compartment is exclusively ACE2-dependent, and whether virus-induced tissue damage and/or direct immune activation largely influence early pathogenesis.  Human lung explants and adult stem cell derived human lung organoids were infected with SARS-CoV-2 and then analyzed using spectral microscopy. 

Single-cell/-nucleus Ribonucleic acid(RNA) sequencing, or ACE2 “gain-of-function” experiments to determine the relationship between ACE2 and other host factors and SARS-CoV-2 tropism, propagation, virulence, and immune activation Middle East respiratory syndrome coronavirus(MERS-CoV). The ex vivo results of coronavirus disease 2019 (COVID-19) were verified using autopsy tissue. Researchers present evidence that suggests SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus are restricted by low levels of alveolar ACE2 expression. In contrast, alveolar macrophages were commonly SARS-CoV-2 positive in ex vivo infected human lungs and COVID-19 autopsy tissues. 

Further investigation with single-cell/-nucleus transcriptomics revealed nonproductive virus uptake and related inflammatory and anti-viral activation, particularly in “inflammatory alveolar macrophages,” similar to that induced by SARS-CoV and MERS-CoV but distinct from that induced by NL63 or influenza virus infection. Overall, their results suggest that the substantial lung injury observed in COVID-19 is not due to direct viral destruction of the alveolar compartment but rather to an immunological activation triggered by macrophages.

Source: erj.ersjournals.com/content/60/6/2102725