{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:21:37Z","timestamp":1790727697128,"version":"4.1.0"},"reference-count":194,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,18]]},"abstract":"<jats:p>Two years after the emergence of SARS-CoV-2, our understanding of COVID-19 disease pathogenesis is still incomplete. Despite unprecedented global collaborative scientific efforts and rapid vaccine development, an uneven vaccine roll-out and the emergence of novel variants of concern such as omicron underscore the critical importance of identifying the mechanisms that contribute to this disease. Overt inflammation and cell death have been proposed to be central drivers of severe pathology in COVID-19 patients and their pathways and molecular components therefore present promising targets for host-directed therapeutics. In our review, we summarize the current knowledge on the role and impact of diverse programmed cell death (PCD) pathways on COVID-19 disease. We dissect the complex connection of cell death and inflammatory signaling at the cellular and molecular level and identify a number of critical questions that remain to be addressed. We provide rationale for targeting of cell death as potential COVID-19 treatment and provide an overview of current therapeutics that could potentially enter clinical trials in the near future.<\/jats:p>","DOI":"10.1042\/bcj20210602","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T11:54:42Z","timestamp":1646394882000},"page":"609-628","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Programmed cell death: the pathways to severe COVID-19?"],"prefix":"10.1042","volume":"479","author":[{"given":"Stefanie M.","family":"Bader","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Cooney","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-3021","authenticated-orcid":false,"given":"Marcel","family":"Doerflinger","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"The Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"2022030411541305100_BCJ-2021-0602CC1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7672","article-title":"Novel human virus? 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