The following is a summary of “Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2 and Necroptosis, Pyroptosis, and PANoptosis,” published in the June 2023 issue of Infectious Diseases by Schifanella, et al.

For a study, researchers sought to investigate the response of alveolar type II (ATII) pneumocytes, which play a crucial role in lung repair, in the context of coronavirus disease 2019 (COVID-19) pneumonia. 

They hypothesized that the initial proliferation of ATII cells during the reparative process could provide many target cells for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus replication, leading to compromised lung repair and disease progression. 

The findings revealed that both infected and uninfected ATII cells are susceptible to different forms of programmed cell death, including tumor necrosis factor-α (TNF)-induced necroptosis, Bruton tyrosine kinase (BTK)-induced pyroptosis, and a novel form of inflammatory cell death called PANoptotic hybrid cell death. This PANoptotic cell death involves the activation of a PANoptosomal latticework, resulting in distinct pathological changes in contiguous ATII cells. 

By identifying TNF and BTK as key initiators of programmed cell death and the cytopathic effects of SARS-CoV-2, they proposed that early antiviral treatment in combination with inhibitors of TNF and BTK could help preserve ATII cell populations, reduce programmed cell death, alleviate hyperinflammation, and restore normal functioning of the alveoli in COVID-19 pneumonia.

Source: academic.oup.com/jid/article/doi/10.1093/infdis/jiad056/7068922