Alveolar Regeneration in COVID-19 Patients: A Network Perspective

Gupta, Shishir; Srivastava, Mugdha; Minocha, Rashmi; Akash, Aman; Dangwal, Seema; Dandekar, Thomas

doi:10.3390/ijms222011279

Cited by 7 publications

(8 citation statements)

References 155 publications

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“…Lethal pneumonia pathogenesis is usually associated with respiratory failure, resulting from cytokine storm-induced airway obstruction or alveolar epithelial damage [ 65 – 69 ]. We found that upregulated glycolysis, OXPHOS, glutathione metabolism, and sphingolipid metabolism may promote AT1 cell aging.…”

Section: Resultsmentioning

confidence: 99%

Cellular metabolic basis of altered immunity in the lungs of patients with COVID-19

Zhao

et al. 2022

Med Microbiol Immunol

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Metabolic pathways drive cellular behavior. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lung tissue damage directly by targeting cells or indirectly by producing inflammatory cytokines. However, whether functional alterations are related to metabolic changes in lung cells after SARS-CoV-2 infection remains unknown. Here, we analyzed the lung single-nucleus RNA-sequencing (snRNA-seq) data of several deceased COVID-19 patients and focused on changes in transcripts associated with cellular metabolism. We observed upregulated glycolysis and oxidative phosphorylation in alveolar type 2 progenitor cells, which may block alveolar epithelial differentiation and surfactant secretion. Elevated inositol phosphate metabolism in airway progenitor cells may promote neutrophil infiltration and damage the lung barrier. Further, multiple metabolic alterations in the airway goblet cells are associated with impaired muco-ciliary clearance. Increased glycolysis, oxidative phosphorylation, and inositol phosphate metabolism not only enhance macrophage activation but also contribute to SARS-CoV-2 induced lung injury. The cytotoxicity of natural killer cells and CD8 + T cells may be enhanced by glycerolipid and inositol phosphate metabolism. Glycolytic activation in fibroblasts is related to myofibroblast differentiation and fibrogenesis. Glycolysis, oxidative phosphorylation, and glutathione metabolism may also boost the aging, apoptosis and proliferation of vascular smooth muscle cells, resulting in pulmonary arterial hypertension. In conclusion, this preliminary study revealed a possible cellular metabolic basis for the altered innate immunity, adaptive immunity, and niche cell function in the lung after SARS-CoV-2 infection. Therefore, patients with COVID-19 may benefit from therapeutic strategies targeting cellular metabolism in future. Supplementary Information The online version contains supplementary material available at 10.1007/s00430-021-00727-0.

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Section: Resultsmentioning

confidence: 99%

Cellular metabolic basis of altered immunity in the lungs of patients with COVID-19

Zhao

et al. 2022

Med Microbiol Immunol

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“…In the case of viral infection, and inflammatory damage is prominent and fibrosis is the dominant process before regeneration. [10,11] Factors such as the amount and types of cells that are damaged, the disruption of barrier function, the intensity and duration of the local immune response can be a predictor of whether the damaged lung regenerates ad integrum or the formation of fibrous tissue leads to chronic lung disease. [5] Study Se-AOX, in which this patient was also included, pointed out, for example, to a significant improvement of respiratory functions quantified on the basis of Carrico index in early selenium adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Full recovery of lung tissue after severe viral pneumonia H1N1: A case report with 10 years follow-up

Kočan¹,

Firment

Pirníková

et al. 2023

Medicine

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Rationale: World healthcare frequently faced severe viral pneumonia cases in the last decades, due to pandemic situations such as H1N1, MERS-CoV, and SARS-COVID-19. Patient concerns: The impact of viral infection on lung structure, lung function, and overall mortality was significant. The quality of life and assumed life expectancy was decreased with the supposed development of lung fibrosis in involved survived patients. Diagnoses: We described the course and treatment of severe pneumonia H1N1 in a 30-year-old patient. Interventions: Patient was included in a study regarding the therapeutic efficacy of selenium ClinicalTrials.gov ID: NCT02026856 with 10 years follow-up with concurrently documented X-ray lung examinations and final histology of lung tissue after sudden death. Outcomes: All sequential examinations and histological findings show a healing trend with the final full recovery of lung tissue.

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“…Several studies on COVID-19 deceased patients confirmed regeneration of damaged lung epithelium following infection, while others showed extensive alveolar damage and lung fibrosis ( 16 ). That such regeneration may in part at least be actively imposed early on as a virus washout mechanism is suggested by a study that compared asymptomatic cases to patients with symptoms and detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic infection ( 119 ).…”

Section: Inflammation: Sars-cov-2 Infection As a Case Studymentioning

confidence: 99%

“…The modularity need not be entirely physical but rather related to the division of work: the modules are viewed as specialized molecular mini networks that respectively mediate and regulate the activation of specific subsets of network “nodes”: proteins mediating signaling cascades, RNA, genes, transcription factors, environmental factors, etc. With the onset of the COVID-19 pandemic, extensive efforts to apply network and control science methods to the host-pathogen interactions are ongoing [reviewed, e.g., ( 16 ). See also ( 17 )].…”

Section: Introductionmentioning

confidence: 99%

An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart

2023

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The systemic bio-organization of humans and other mammals is essentially “preprogrammed”, and the basic interacting units, the cells, can be crudely mapped into discrete sets of developmental lineages and maturation states. Over several decades, however, and focusing on the immune system, we and others invoked evidence – now overwhelming – suggesting dynamic acquisition of cellular properties and functions, through tuning, re-networking, chromatin remodeling, and adaptive differentiation. The genetically encoded “algorithms” that govern the integration of signals and the computation of new states are not fully understood but are believed to be “smart”, designed to enable the cells and the system to discriminate meaningful perturbations from each other and from “noise”. Cellular sensory and response properties are shaped in part by recurring temporal patterns, or features, of the signaling environment. We compared this phenomenon to associative brain learning. We proposed that interactive cell learning is subject to selective pressures geared to performance, allowing the response of immune cells to injury or infection to be progressively coordinated with that of other cell types across tissues and organs. This in turn is comparable to supervised brain learning. Guided by feedback from both the tissue itself and the neural system, resident or recruited antigen-specific and innate immune cells can eradicate a pathogen while simultaneously sustaining functional homeostasis. As informative memories of immune responses are imprinted both systemically and within the targeted tissues, it is desirable to enhance tissue preparedness by incorporating attenuated-pathogen vaccines and informed choice of tissue-centered immunomodulators in vaccination schemes. Fortunately, much of the “training” that a living system requires to survive and function in the face of disturbances from outside or within is already incorporated into its design, so it does not need to deep-learn how to face a new challenge each time from scratch. Instead, the system learns from experience how to efficiently select a built-in strategy, or a combination of those, and can then use tuning to refine its organization and responses. Efforts to identify and therapeutically augment such strategies can take advantage of existing integrative modeling approaches. One recently explored strategy is boosting the flux of uninfected cells into and throughout an infected tissue to rinse and replace the infected cells.

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Alveolar Regeneration in COVID-19 Patients: A Network Perspective

Cited by 7 publications

References 155 publications

Cellular metabolic basis of altered immunity in the lungs of patients with COVID-19

Cellular metabolic basis of altered immunity in the lungs of patients with COVID-19

Full recovery of lung tissue after severe viral pneumonia H1N1: A case report with 10 years follow-up

An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart

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