{"doi":"10.1093/infdis/jiad056","title":"The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2 and Necroptosis, Pyroptosis, and PANoptosis","abstract":"Alveolar type II (ATII) pneumocytes as defenders of the alveolus are critical to repairing lung injury. We investigated the ATII reparative response in coronavirus disease 2019 (COVID-19) pneumonia, because the initial proliferation of ATII cells in this reparative process should provide large numbers of target cells to amplify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus production and cytopathological effects to compromise lung repair. We show that both infected and uninfected ATII cells succumb to tumor necrosis factor-α (TNF)-induced necroptosis, Bruton tyrosine kinase (BTK)-induced pyroptosis, and a new PANoptotic hybrid form of inflammatory cell death mediated by a PANoptosomal latticework that generates distinctive COVID-19 pathologies in contiguous ATII cells. Identifying TNF and BTK as the initiators of programmed cell death and SARS-CoV-2 cytopathic effects provides a rationale for early antiviral treatment combined with inhibitors of TNF and BTK to preserve ATII cell populations, reduce programmed cell death and associated hyperinflammation, and restore functioning alveoli in COVID-19 pneumonia.","journal":"The Journal of Infectious Diseases","year":2023,"id":331463,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":908669,"name":"Jodi Anderson","orcid":null,"position":1,"is_corresponding":false},{"id":1056841,"name":"Garritt Wieking","orcid":null,"position":2,"is_corresponding":false},{"id":678787,"name":"Peter J. Southern","orcid":"0000-0002-9343-0653","position":3,"is_corresponding":false},{"id":1056423,"name":"Spinello Antinori","orcid":"0000-0003-0569-9407","position":4,"is_corresponding":false},{"id":225093,"name":"Massimo Galli","orcid":"0000-0001-8887-6215","position":5,"is_corresponding":false},{"id":1056424,"name":"Mario Corbellino","orcid":"0000-0002-9524-8564","position":6,"is_corresponding":false},{"id":1056425,"name":"Alessia Lai","orcid":"0000-0002-3174-5721","position":7,"is_corresponding":false},{"id":332551,"name":"Nichole R. Klatt","orcid":"0000-0003-2968-5480","position":8,"is_corresponding":false},{"id":387532,"name":"Timothy W. Schacker","orcid":"0000-0002-2451-9937","position":9,"is_corresponding":false},{"id":548254,"name":"Ashley T. Haase","orcid":"0000-0002-5374-2388","position":10,"is_corresponding":false},{"id":397732,"name":"Luca Schifanella","orcid":"0000-0002-6123-536X","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T01:09:19.317824Z","pmid":"36869698","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}