From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8290 - 8290

Опубликована: Май 5, 2023

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given diversity characteristic cellular phenotype, possible cytopathic, and clinical effects are difficult predict, determines heterogeneity COVID-19 symptoms. The purpose this article provide a comprehensive review cytopathic SARS-CoV-2 on cell types, focusing development COVID-19, may lead, some patients, persistence symptoms after recovery disease, condition known as long COVID. We describe mechanisms underlying virus-host interactions, including alterations protein expression, intracellular signaling pathways, immune responses. In particular, highlights potential impact these cytopathies function outcomes, such dysregulation, neuropsychiatric disorders, organ damage. concludes discussing future directions for research implications management treatment

Язык: Английский

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Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation

Science Immunology, Год журнала: 2023, Номер 8(86)

Опубликована: Авг. 4, 2023

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with lung-migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance survival of human-ACE2 transgenic mice challenged SARS-CoV-2 (SCV2). This protection is associated lymphocytic infiltrate, including increased accumulation pulmonary SCV2-specific CD8+ T cells, anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in loads. Pulmonary macrophages type 2 transcriptional epigenetic signature persist lungs brasiliensis-exposed after parasite establish primed environment for cell recruitment activation. Accordingly, ablated augmented cells driven by brasiliensis infection. Together, these findings support concept helminths can limit disease severity during SCV2 through macrophage-dependent enhancement antiviral responses.

Язык: Английский

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Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection

JCI Insight, Год журнала: 2023, Номер 8(1)

Опубликована: Янв. 9, 2023

Substantial clinical evidence supports the notion that ciliary function in airways is important COVID-19 pathogenesis. Although damage has been observed both vitro and vivo models, extent or nature of impairment mucociliary transport (MCT) models remains unknown. We hypothesize SARS-CoV-2 infection results MCT deficiency golden Syrian hamsters precedes pathological injury lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes apparatus. Both genomic subgenomic viral RNA physiological were monitored parallel. show caused a 67% decrease rate as early 2 days postinfection (dpi) hamsters, principally due 79% diminished airway coverage motile cilia. Correlating quantitation physiological, virological, reveals steadily descending from upper lower parenchyma within 7 dpi. Our indicate deficits apparatus are key aspect pathogenesis, may extend retention, could pose risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell disease progression. Therapies directed toward deserve further investigation.

Язык: Английский

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Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells

Journal of Allergy and Clinical Immunology, Год журнала: 2023, Номер 152(1), С. 56 - 67

Опубликована: Март 29, 2023

Язык: Английский

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Chemosensory cells in the respiratory tract as crucial regulators of innate immune responses

The Journal of Physiology, Год журнала: 2023, Номер 601(9), С. 1555 - 1572

Опубликована: Апрель 3, 2023

During recent years chemosensory cells in extraoral tissues have been established as mediators for the detection and regulation of innate immune processes response to pathogens. Under physiological conditions, are present throughout respiratory epithelium upper lower airways well main olfactory epithelium. Additionally, they emerge alveolar region lung upon viral infections. Chemosensory detect signalling molecules from gram-positive gram-negative bacteria aeroallergens fungi. Upon stimulation release multiple molecules, such transmitter acetylcholine, cysteinyl leukotriene E4 cytokine interleukin-25, which act autocrine paracrine signals thereby orchestrate responses system. Activation stimulates various cells, e.g. type 2 lymphoid modulates mucociliary clearance induces a protective neurogenic inflammation. This review compiles discusses findings regarding cell function tract.

Язык: Английский

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Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 268, С. 116263 - 116263

Опубликована: Фев. 24, 2024

Язык: Английский

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Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system

The Lancet Digital Health, Год журнала: 2024, Номер 6(5), С. e309 - e322

Опубликована: Апрель 24, 2024

In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on patient population studied. We aimed to analyse severe investigate effects pandemic time period risks associated with individual IMIDs, classes immunomodulatory medications (IMMs), chronic comorbidities, vaccination status.

Язык: Английский

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Cell Culture Differentiation and Proliferation Conditions Influence the In Vitro Regeneration of the Human Airway Epithelium

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2024, Номер 71(3), С. 267 - 281

Опубликована: Июнь 6, 2024

The human airway mucociliary epithelium can be recapitulated

Язык: Английский

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Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial

Open Forum Infectious Diseases, Год журнала: 2022, Номер 9(8)

Опубликована: Июль 27, 2022

Abstract Background Based on studies implicating the type 2 cytokine interleukin 13 (IL-13) as a potential contributor to critical coronavirus disease 2019 (COVID-19), this trial was designed an early phase study assess dupilumab, monoclonal antibody that blocks IL-13 and 4 signaling, for treatment of inpatients with COVID-19. Methods We conducted 2a randomized, double-blind, placebo-controlled (NCT04920916) safety efficacy dupilumab plus standard care vs placebo in mitigating respiratory failure death those hospitalized Results Forty eligible subjects were enrolled from June November 2021. There no statistically significant difference adverse events nor primary endpoint ventilator-free survival at day 28 between arms. However, secondary mortality 60, there deaths group compared 5 (60-day survival: 89.5% 76.2%; adjusted hazard ratio [HR], 0.05 [95% confidence interval {CI}, .004–.72]; P = .03). Among who not intensive unit (ICU) randomization, 3 arm admitted ICU 6 (17.7% 37.5%; HR, 0.44 CI, .09–2.09]; .30). Last, we found evidence signaling blockade through analysis immune biomarkers over time. Conclusions Although outcome reached, observed higher by 60. Clinical Trials Registration NCT04920916.

Язык: Английский

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NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 4, 2024

Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response arising viral variants are needed. Here we describe an adult stem cell-derived human organoid model overexpressing ACE2 receptor (ACE2-OE) supports robust replication while maintaining 3D architecture and cellular diversity of epithelium. ACE2-OE organoids were infected with subjected single-cell RNA-sequencing. Interferon-lambda was upregulated in cells low-level infection NF-kB inhibitor alpha gene (encoding IkBa) consistently cells, its expression positively correlated levels. Confocal microscopy showed more IkBa than bystander but found concurrent nuclear translocation usually prevents. Overexpressing a nondegradable mutant reduced increased infection. These data demonstrate functionality research underscore strength feedback loop controls replication.

Язык: Английский

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