Restoration of Type 17 immune signaling is not sufficient for protection during influenza-associated pulmonary aspergillosis DOI Creative Commons
Aijaz Ahmad, Rupa Singh, Kara L. Nickolich

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Introduction Influenza-associated pulmonary aspergillosis (IAPA) is a severe complication of influenza infection that occurs in critically ill patients and results higher mortality compared to alone. Interleukin-17 (IL-17) the Type 17 immune signaling pathway cytokine family are recognized for their pivotal role fostering protective immunity against various pathogens. In this study, we investigate IL-17 components during IAPA. Methods Wild-type mice were challenged with A H1N1 (flu) then exposed Aspergillus fumigatus ATCC42202 resting conidia on day 6 post-influenza infection, followed by quantification cytokines chemokines at 48 h post-fungal infection. Results discussion The gene protein expression levels revealed antimicrobial peptides downregulated IAPA singularly infected solely A. . Restoration was not sufficient provide protection increased fungal burden observed These findings contrast those bacterial super-infection, which restoration protects exacerbation seen super-infection. Our study highlights need future studies understand mechanisms increase susceptibility

Language: Английский

Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease DOI
Martin Hoenigl, Amir Arastehfar, Maiken Cavling Arendrup

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: April 11, 2024

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, their utility efficacy in antifungal treatment limited one or more of innate acquired resistance some fungi, poor penetration into "sequestered" sites, agent-specific side effect which require frequent patient reassessment monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, fungicidal mechanism(s) urgently needed. Here, we provide comprehensive review agents, both improved known mechanisms actions new currently clinical development for treating invasive yeast, mold (filamentous fungi),

Language: Английский

Citations

33
Risk factors for COVID-19-associated pulmonary aspergillosis: a systematic review and meta-analysis DOI
Francesca Gioia, Laura N. Walti, Ani Orchanian‐Cheff

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(3), P. 207 - 216

Published: Jan. 4, 2024

Language: Английский

Citations

25
Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patients DOI
Simon Feys, Agostinho Carvalho, Cornelius J. Clancy

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(9), P. 728 - 742

Published: July 15, 2024

Language: Английский

Citations

17
Pathogenicity and virulence of Aspergillus fumigatus DOI Creative Commons
Kayleigh Earle, Clara Valero, Daniel P. Conn

et al.

Virulence, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 8, 2023

Pulmonary infections caused by the mould pathogen Aspergillus fumigatus are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral bacterial pulmonary recognised risks factors for development aspergillosis. In this review, we will summarise our current knowledge mechanistic basis aspergillosis with focus on emerging at-risk populations.

Language: Английский

Citations

41
Metagenomic Next-Generation Sequencing of Plasma for Diagnosis of COVID-19-Associated Pulmonary Aspergillosis DOI
Martin Hoenigl, Matthias Egger,

Jessica S. Price

et al.

Journal of Clinical Microbiology, Journal Year: 2023, Volume and Issue: 61(3)

Published: Feb. 21, 2023

Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which its early stages is characterized by tissue-invasive growth of the lungs limited angioinvasion. Currently available mycological tests show sensitivity when testing blood specimens.

Language: Английский

Citations

36
Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading DOI Creative Commons
Johannes Boyer, Simon Feys,

Isabella Zsifkovits

et al.

Mycopathologia, Journal Year: 2023, Volume and Issue: 188(5), P. 667 - 681

Published: April 26, 2023

Abstract Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients hence vulnerable hosts increases, which is paralleled by emergence rise IA cases. Increased frequencies azole-resistant strains are reported from six continents, presenting new challenge for therapeutic management. Treatment options currently consist three classes antifungals (azoles, polyenes, echinocandins) with distinctive advantages shortcomings. Especially settings difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches urgently needed. Promising drugs late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix Gwt1 enzyme ibrexafungerp triterpenoid), opelconazole (an azole optimized inhalation) rezafungin echinocandin long half-life time). Further, insights pathophysiology yielding immunotherapy as potential add-on therapy. Current investigations show encouraging results, so far mostly preclinical settings. In this review we discuss current strategies, give an outlook on possible pharmaceutical options, and, lastly, provide overview ongoing research IA.

Language: Английский

Citations

31
High Burden of COVID-19-Associated Pulmonary Aspergillosis in Severely Immunocompromised Patients Requiring Mechanical Ventilation DOI Creative Commons
Simon Feys, Katrien Lagrou,

Hanne Moon Lauwers

et al.

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 78(2), P. 361 - 370

Published: Sept. 11, 2023

Abstract Background Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and associated increased mortality rates. The increasing proportion of severely immunocompromised who require mechanical ventilation warrants research into the incidence impact CAPA during vaccination era. Methods We performed retrospective, monocentric, observational study. collected data from adult severe requiring were admitted to intensive care unit (ICU) University Hospitals Leuven, tertiary referral center, between 1 March 2020 14 November 2022. Probable or proven was diagnosed according European Confederation for Medical Mycology/International Society Human Animal Mycology (ECMM/ISHAM) criteria. Results included 335 patients. Bronchoalveolar lavage sampling 300 (90%), 112 (33%). 62% (50 81 patients) Organisation Research Treatment Cancer (EORTC)/Mycosis Study Group Education Consortium (MSGERC) host factor–positive patients, compared 24% (62 254) factor–negative significantly higher era, (57 241) ICU before October 2021 59% (55 94) those since then. Both EORTC/MSGERC factors admission era independently development. remained an independent risk factor Conclusions presence invasive mold worse outcome parameters, it main driver Our findings warrant investigation antifungal prophylaxis COVID-19.

Language: Английский

Citations

25
Lower respiratory tract single-cell RNA sequencing and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis: a single centre, retrospective, observational study DOI Creative Commons
Simon Feys, Sam Vanmassenhove, Sirima Kraisin

et al.

The Lancet Microbe, Journal Year: 2024, Volume and Issue: 5(3), P. e247 - e260

Published: Jan. 24, 2024

BackgroundCOVID-19-associated pulmonary aspergillosis (CAPA) is a severe superinfection with the fungus Aspergillus affecting patients who are critically ill COVID-19. The pathophysiology and role of neutrophil extracellular traps (NETs) in this infection largely unknown. We aimed to characterise immune profile, focus on neutrophils NET concentrations, COVID-19, or without CAPA.MethodsWe conducted single-centre, retrospective, observational study two patient cohorts, both recruited at University Hospitals Leuven, Belgium. included adults aged 18 years older were admitted intensive care unit because COVID-19 between March 31, 2020, May 18, 2021, previous Contagious trial (NCT04327570). investigated cellular landscape CAPA versus only by performing single-cell RNA sequencing (scRNA-seq) bronchoalveolar lavage fluid. Bronchoalveolar cell fractions compared only. Additionally, we determined lower respiratory tract concentrations using biochemical assays 15, Dec for whom was available hospital biobank. integrated existing data mediators 90-day mortality.FindingsWe performed scRNA-seq 43 samples from 39 patients, 36 (30 male six female; 14 CAPA) downstream analyses. analyses 59 (46 13 female), 26 had CAPA. By scRNA-seq, significantly than (16% vs 33%; p=0·0020). remaining preferentially followed hybrid maturation trajectory characterised expression genes linked antigen presentation, enhanced transcription antifungal effector pathways. Patients also showed depletion mucosal-associated invariant T cells, reduced helper 1 17 differentiation, transcriptional defects specific aspects immunity macrophages monocytes. observed increased formation NETs (DNA complexed citrullinated histone H3 median 15 898 ng/mL [IQR 4588–86 419] 7062 [775–14 088]; p=0·042), thereby explaining decreased scRNA-seq. Low associated mortality CAPA.InterpretationQualitative quantitative disturbances monocyte, macrophage, B-cell, T-cell populations could predispose develop Hybrid form specialised response CAPA, an adequate major determinant survival these patients. Therefore, measuring have diagnostic prognostic value Clinicians should be wary when immunomodulatory therapy that might inhibit NETosis treat COVID-19.FundingResearch Foundation Flanders, KU UZ VIB, Fundação para Ciência e Tecnologia, European Regional Development Fund, la Caixa Foundation, Flemish Government, Horizon 2020.

Language: Английский

Citations

13
A multivariable prediction model for invasive pulmonary aspergillosis in immunocompromised patients with acute respiratory failure (IPA-GRRR-OH score) DOI

Alice Friol,

Guillaume Dumas, Frédéric Pène

et al.

Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Language: Английский

Citations

1
Recent developments in Aspergillus fumigatus research: diversity, drugs, and disease DOI
Nicole Kordana, Angus Johnson, Karen Quinn

et al.

Microbiology and Molecular Biology Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

SUMMARY Advances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infections caused by the environmental mold Aspergillus fumigatus . As contemporary antifungal not experienced same robust advances as other therapies, defining mechanisms of A. initiation and progression remains a critical research priority. To this end, World Health Organization recently identified priority pathogen Centers Disease Control has highlighted emergence triazole-resistant isolates. The expansion diversity host populations susceptible aspergillosis complex dynamic genotypic phenotypic call reinvigorated assessment pathobiological drug-susceptibility mechanisms. Here, we summarize recent advancements field discuss challenges our understanding heterogeneity its pathogenesis diverse populations.

Language: Английский

Citations

1