Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

Li, Xue; Zhang, Ziqi; Wang, Zhenling; Gutiérrez‐Castrellón, Pedro; Shi, Huashan

doi:10.1038/s41392-022-01043-6

Cited by 43 publications

(33 citation statements)

References 325 publications

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“…Most COVID-19 complications occur due to the dysregulated immune response caused by SARS-CoV-2 infection. Inflammation and cell death have been proposed as major mechanisms underlying severe COVID-19 [28][29][30][31]. Our findings indicate that the wild-type and the Delta variant result in a more pronounced upregulation of TLR, cytokine, and chemokine genes compared to the Omicron variant.…”

Section: Discussionmentioning

confidence: 58%

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Kuruppuarachchi¹,

Jang²,

Seo³

2022

Front. Biosci. (Landmark Ed)

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Background:The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 therapeutics. This study aimed to compare the expression patterns of genes involved in immune responses in K18-hACE2 mice infected with the wild-type, Delta, and Omicron SARS-CoV-2 variants. Methods: K18-hACE2 mice were intranasally infected with either wild-type (B.1), Delta (B.1.617.2), or Omicron (B.1.1.529) variants. On day 6 post-infection, lung, brain, and kidney tissues were collected from each variantinfected group. The mRNA expression levels of 39 immune response genes in all three groups were compared by RT-qPCR. Viral titers were measured using the median tissue culture infectious dose (TCID50) assay and expressed as Log10 TCID50/0.1 g. The statistical significance of the differences in gene expression was determined by one-way analysis of variance (ANOVA) (alpha = 0.05). Results: The expression of toll-like receptors (TLRs) was upregulated in the lung and brain tissues of the wild-type-and Delta-infected groups but not in those of the Omicron-infected group. The highest expression of cytokines, including interleukin (IL)-1α, IL-1β, IL-17α, interferon, and tumor necrosis factors, was observed in the lungs of mice infected with the wild-type variant. Additionally, CCL4, CCL11, CXCL9, and CXCL10 were upregulated (>3-fold) in wild-type-infected mice, with markedly higher expressions in the brain than in the lungs. Most of the apoptotic factors were mainly expressed in the brain tissues of Omicron-infected mice (caspase 8, caspase 9, p53, Bax, Bak, BCL-2, and Bcl-XL), whereas neither the lung nor kidney showed more than 3-fold upregulation of these apoptotic factors. Conclusions: Collectively, our findings revealed that the wild-type SARS-CoV-2 variant exhibited the highest pathogenicity, followed by the Delta variant, then the Omicron variant.

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Section: Discussionmentioning

confidence: 58%

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Kuruppuarachchi¹,

Jang²,

Seo³

2022

Front. Biosci. (Landmark Ed)

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“…Interaction of DAMPs with pattern-recognition receptors (PRRs), including Toll-like receptors and NLRP3 inflammasome of the adjacent parenchymal cells or immune cells, promotes the production of various pro-inflammatory cytokines and chemokines [ 31 , 34 , 35 , 36 ]. Of note, cell death pathways (e.g., autophagy, NETosis, pyroptosis, apoptosis, necroptosis, and ferroptosis) in surrounding immune cells and stromal cells are activated, fueling the cytokine storm and cultivating a positive cell death-inflammation feedback loop [ 30 , 37 , 38 ]. In COVID-19, virus particles themselves act as pathogen-associated molecular patterns (PAMPs), which could also be identified by PRRs and activate local inflammation and an innate immune response, evoking the cytokine storm and assembling those induced by DAMPs [ 29 , 39 ].…”

Section: Pathogenesis and Immunopathology In Ap And Covid-19mentioning

confidence: 99%

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19

Liu

Luo

Szatmary

et al. 2023

IJMS

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Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR−/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

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“…There is now growing evidence that ferroptosis is involved in the pathogenesis of COVID-19 ( Li et al, 2022 ). Ferroptosis has been detected in human heart ( Jacobs et al, 2020 ) and hamster lung ( Han et al, 2022 ) samples infected with SARS-CoV-2.…”

Section: Ferroptosis and Infectious Airway Inflammatory Diseasesmentioning

confidence: 99%

The link between ferroptosis and airway inflammatory diseases: A novel target for treatment

Lin

Yang

Guan

et al. 2022

Front. Mol. Biosci.

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Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.

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Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19

Cited by 43 publications

References 325 publications

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19

The link between ferroptosis and airway inflammatory diseases: A novel target for treatment

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