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Programmed cell death: the pathways to severe COVID-19?
Stefanie M Bader1,2, James P Cooney1,2, Marc Pellegrini1,2
1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Abstract:
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.
Insights
Programmed cell death (PCD) pathways significantly impact severe COVID-19. Understanding these mechanisms and inflammation is crucial for developing new host-directed therapeutics against SARS-CoV-2 variants.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- COVID-19 pathogenesis remains incompletely understood despite extensive research.
- Emerging SARS-CoV-2 variants and uneven vaccine distribution highlight the need for alternative treatments.
- Overt inflammation and programmed cell death (PCD) are implicated in severe COVID-19 pathology.
Purpose of the Study:
- To review current knowledge on the role of diverse PCD pathways in COVID-19.
- To dissect the molecular links between cell death and inflammatory signaling in COVID-19.
- To identify critical unanswered questions and potential therapeutic targets.
Main Methods:
- Literature review of programmed cell death pathways in COVID-19.
- Analysis of cellular and molecular mechanisms connecting inflammation and cell death.
- Evaluation of potential host-directed therapeutic strategies.
Main Results:
- Programmed cell death pathways are integral to COVID-19 disease progression.
- Complex interplay exists between cell death signaling and inflammatory responses.
- Several critical questions regarding PCD in COVID-19 require further investigation.
Conclusions:
- Targeting cell death pathways presents a promising strategy for COVID-19 treatment.
- Further research is needed to elucidate specific PCD mechanisms in COVID-19.
- Existing therapeutics targeting cell death warrant clinical evaluation for COVID-19.
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