Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

Pharmaceuticals, Год журнала: 2023, Номер 16(7), С. 924 - 924

Опубликована: Июнь 25, 2023

Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite World Health Organization’s recommendation against their use at beginning of pandemic, GCs a dose equivalent to dexamethasone 6 mg/day 10 days are now indicated in all COVID-19 cases who require respiratory support. However, intervention depends on timing initiation, dose, other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate presence comorbidities or severity involvement baseline. This prompted us critically review literature rationale, principles, clinical evidence that should guide treatment. Based these data, best treatment protocol probably involves an initial bolus saturate glucocorticoid receptors, followed by continuous infusion maintain constant plasma levels, eventually slow tapering interruption. Methylprednisolone has molecules, most likely thanks its higher ability penetrate lung. Decreased tissue sensitivity is thought be main mechanism accounting lower response some individuals. We readily available test identify resistance; therefore, address inter-individual variability, future research aim investigating clinical, physiological, laboratory markers personalized approach.

Язык: Английский

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Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series

Pathobiology, Год журнала: 2023, Номер 91(2), С. 158 - 168

Опубликована: Июль 25, 2023

<b><i>Background:</i></b> Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce. <b><i>Objectives:</i></b> This case series seeks to characterize the intra-alveolar immunopathology of COVID-19. <b><i>Method:</i></b> BALs were performed 14 (5 COVID-19, which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (<i>n</i> = 1), unremarkable 3), infections with respiratory syncytial virus influenza B other coronaviruses 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while detection pathogens immunofluorescence or multiplex NAT. <b><i>Results:</i></b> Gene expression profiling showed 71 significantly downregulated 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated genes involved macrophage development, polarization, crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), chemokine signaling immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated featured NK-T cell (GZMA, GZMH, GNLY, PRF1, CD3G). Patients a significant upregulation blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), zinc metalloprotease elevated (CPA3) compared asymptomatic cases. In-silico comparison BAL cases published cohort lethal “antigen processing presentation” “lysosome” pathways <b><i>Conclusions:</i></b> These underscore heterogeneity immune Further studies larger dataset required gain better understanding hallmarks immunological response.

Язык: Английский

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Activation of CD3 + TIM3 + T cells contributes to excessive inflammatory response during glucocorticoid treatment

Biochemical Pharmacology, Год журнала: 2023, Номер 212, С. 115551 - 115551

Опубликована: Апрель 10, 2023

Язык: Английский

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Drug-Induced Acute Pancreatitis in Hospitalized COVID-19 Patients

Diagnostics, Год журнала: 2023, Номер 13(8), С. 1398 - 1398

Опубликована: Апрель 12, 2023

Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, is a systemic disease that affects not only the respiratory system, but also other systems, including gastrointestinal. A great number of different drugs have been used on hospitalized patients for management COVID-19, and acute pancreatitis (AP) has reported as complication or side effect these drugs. The development drug-induced (DIAP) follows complex pathophysiological mechanisms, particular risk factors play key role. Diagnosis DIAP depends specific criteria, based these, drug may be characterized having definite, probable possible connection with AP. aim this review to present medications are COVID-19 associated AP in patients. list mainly includes corticosteroids, glucocorticoids, non-steroidal anti-inflammatory (NSAIDs), antiviral agents, antibiotics, monoclonal antibodies, estrogens anesthetic agents. Moreover, prevention vital, especially critically ill who receive multiple non-invasive first step concerns exception suspicious from therapy.

Язык: Английский

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Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury

Science Translational Medicine, Год журнала: 2024, Номер 16(767)

Опубликована: Окт. 2, 2024

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity mortality represents common complication in critically ill patients COVID-19. In AKI, renal tubular epithelial cells (TECs) are primary site of damage, recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation maladaptation TECs remain largely unclear. Here, our study an autopsy cohort COVID-19 provided evidence that by myoglobin, released as consequence rhabdomyolysis, major pathophysiological mechanism for severe Analyses human biopsies, mouse models myoglobinuric gentamicin-induced tubuloids showed resulted activation glucocorticoid receptor endogenous glucocorticoids, which aggravated damage. The detrimental effect glucocorticoids injured was exacerbated administration widely clinically used synthetic glucocorticoid, dexamethasone, indicated experiments myoglobinuric- folic acid–induced tubuloids, slice cultures. Mechanistically, studies cultures demonstrated signaling orchestrated maladaptive transcriptional program to hinder DNA repair, amplify injury-induced double-strand break formation, dampen mTOR activity mitochondrial bioenergetics. This identifies maladaptation, functionally important AKI.

Язык: Английский

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Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID‐19 Outcomes: A Population‐Based Cohort Study

ACR Open Rheumatology, Год журнала: 2023, Номер 5(12), С. 685 - 693

Опубликована: Окт. 11, 2023

We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure severe COVID-19 outcomes in a population-based cohort study.Participants were 18 years or older, tested positive for SARS-CoV-2 February 6, 2020, August 15, 2021, from administrative health data entire province of British Columbia, Canada. IIA use within 3 months prior to test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, non-TNFi targeted synthetic (tsDMARDs) (rituximab separately abatacept, anakinra, secukinumab, tocilizumab, tofacitinib ustekinumab glucocorticoids. Severe hospitalizations COVID-19, ICU admissions, deaths 60 days test. Exposure score-overlap weighting was used balance baseline characteristics participants with compared nonuse that IIA. Logistic regression measured outcomes.From 147,301 participants, we identified 515 antimalarial, 573 72 180 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other biologic tsDMARD, 1348 glucocorticoid prescriptions. Risk significantly greater MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], glucocorticoids: 1.63 [1.36-1.96], relative nonuse. Similar seen admission MMF: 2.52 [1.34-4.74], 2.88 [1.73-4.78], 1.86 [1.37-2.54]. Only glucocorticoids associated significant increase 60-day mortality: 1.58 [1.21-2.06]. No IIAs displayed statistically associations outcomes.Current an increased risk These results emphasize variety circumstances patients taking IIAs.

Язык: Английский

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A Neonate With Cytokine Storm Managed With Steroids, Therapeutic Plasma Exchange, and Tocilizumab

Cureus, Год журнала: 2023, Номер unknown

Опубликована: Сен. 12, 2023

Neonatal cytokine storms, though rare, can induce hyperinflammation due to elevated interleukin-6 (IL-6), triggering multiorgan failure. We present the case of a term male neonate necessitating extracorporeal membrane oxygenation (ECMO) post-birth for persistent pulmonary hypertension meconium aspiration syndrome. Three days after weaning from ECMO support, steroids and therapeutic plasma exchange were initiated deteriorating thrombocytopenia, oxygenation, hemodynamic instability, increased C-reactive protein (CRP) ferritin levels. Elevated IL-6 prompted tocilizumab administration four daily plasmapheresis. Post-tocilizumab infusion, notable enhancements in platelet counts, indices, CRP observed, resulting stable discharge child. Comprehensive evaluations infections, including coronavirus disease 2019, as well genetic metabolic disorders, yielded negative results.

Язык: Английский

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Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 25, 2023

Abstract Cis-regulatory elements (CREs) control gene transcription dynamics across cell types and in response to the environment. In asthma, multiple immune play an important role inflammatory process. Genetic variants CREs can also affect expression contribute asthma risk. However, regulatory mechanisms underlying of transcriptional different environmental contexts cell-types at single resolution remains be elucidated. To resolve this question, we performed scATAC-seq activated peripheral blood mononuclear cells (PBMC) from 16 children with phytohemagglutinin (PHA) or lipopolysaccharide (LPS), treated dexamethasone (DEX), antiinflammatory glucocorticoid. We analyzed changes chromatin accessibility, measured factor motif activity, identified treatment cell-type specific factors that drive both mean variability. observed strong positive linear dependence between their target changes, but negative variability changes. This result suggests increase binding tightens around mean. then annotated genetic accessibility peaks motifs followed by computational fine-mapping eQTL signals a pediatric cohort. found eQTLs were 5-fold enriched refined credible set for 410 risk genes, 191 having causal variant motifs. conclusion, enhances understanding molecular mediated expression.

Язык: Английский

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Steroid hormones and infection and immunity

Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 79 - 105

Опубликована: Янв. 1, 2024

Язык: Английский

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Wedge Resection and Optimal Solutions for Invasive Pulmonary Fungal Infection and Long COVID Syndrome—A Case Report and Brief Literature Review

Reports — Medical Cases Images and Videos, Год журнала: 2024, Номер 7(2), С. 25 - 25

Опубликована: Апрель 5, 2024

A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by new coronavirus pandemic. 62-year-old female patient was admitted a form Coronavirus disease 2019 (COVID-19) and spent four weeks intensive care unit (ICU) requiring mechanical ventilation support before being moved to tertiary for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., positive bacteriology multidrug-resistant Klebsiella pneumoniae Proteus mirabilis were identified bronchial aspirate cultures. The patient’s progress gradually encouraging while receiving oral antifungal broad-spectrum antibiotic therapy along respiratory physical therapy; but ultimately, thoracic surgery necessary. Long-lasting tissue damage severe, persistent inflammatory syndrome two main pathophysiological mechanisms that led significant outcomes regarding lung lesions rapidly colonized fungi resistant flora, cardiac sinus tachycardia at slightest effort, chronic syndrome, which characterized marked asthenia, myalgias, exercise intolerance.

Язык: Английский

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