SARS-CoV-2 in immunocompromised individuals

Immunity, Journal Year: 2022, Volume and Issue: 55(10), P. 1779 - 1798

Published: Sept. 13, 2022

Language: Английский

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Corticosteroids and superinfections in COVID-19 patients on invasive mechanical ventilation

Journal of Infection, Journal Year: 2022, Volume and Issue: 85(1), P. 57 - 63

Published: May 21, 2022

To determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients, impact dexamethasone as standard therapy.This multicentre, observational, retrospective study included patients ≥ 18 years admitted from March 1st 2020 to January 31st 2021 with infection who received mechanical ventilation. Patient characteristics, clinical therapy survival were examined.155/156 (115 men, mean age 62 years, range 26-84 years) included. 67 (43%) had 90 superinfections, pneumonia dominated (78%). Superinfections associated receiving (66% vs 32%, p<0.0001), autoimmune disease (18% 5.7%, p<0.016) longer ICU stays (26 17 days, p<0,001). Invasive fungal infections reported exclusively dexamethasone-treated [8/67 (12%) 0/88 (0%), p<0.0001]. Unadjusted 90-day did not differ between or without (64% 73%, p=0.25), but was lower versus (58% 78%, p=0.007). In multiple regression analysis, superinfection use [OR 3.7 (1.80-7.61), p<0.001], pre-existing 3.82 (1.13-12.9), p=0.031] length stay 1.05 p<0.001].In critically ill care strongly independently superinfections.

Language: Английский

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Immunity to fungi in the lung

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 66, P. 101728 - 101728

Published: Feb. 24, 2023

Language: Английский

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Prevalence of COVID-19-Associated Pulmonary Aspergillosis: Critical Review and Conclusions

Journal of Fungi, Journal Year: 2022, Volume and Issue: 8(4), P. 390 - 390

Published: April 12, 2022

First reports of cases and case series COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months pandemic. Prevalence rates varied widely due to fact that CAPA was, still remains, challenging diagnose in patients with acute respiratory failure (ARF). The clinical picture radiological findings are unspecific can resemble those severe COVID-19. Hence, mycological evidence became a key component establishing diagnosis. However, blood tests lack sensitivity early treatable phases once positive, mortality has been shown exceed 80% despite systemic antifungal therapy. primarily airway invasive growth non-neutropenic late occurrence angioinvasion course disease may mainly account for these diagnostic obstacles. Testing bronchoalveolar lavage (BAL) is therefore crucial process, but was rarely performed phase pandemic, which potentially interfered accuracy reported prevalence. Current guidelines recommend treatment its phase, result some overtreatment (i.e., not develop angioinvasive infection) adverse drug events, yet there no viable alternative approach. Timely needs be ensured lower tract given independent contribution devastating around 50% have multiple studies. Here, we review evolution prevalence role as an important opportunistic infection affecting COVID-19 intensive care units (ICUs).

Language: Английский

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High Burden of COVID-19-Associated Pulmonary Aspergillosis in Severely Immunocompromised Patients Requiring Mechanical Ventilation

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

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The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4318 - 4335.e20

Published: July 3, 2024

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action unknown, and many patients deteriorate or die despite timely initiation. Here, we identify dexamethasone treatment-induced cellular molecular changes associated with improved survival in COVID-19 patients. We observed reversal transcriptional hallmark signatures monocytes the induction monocyte substate characterized by expression glucocorticoid-response genes. These responses to were detected circulating pulmonary monocytes, they directly linked survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived enriched whole blood transcriptomes fatal outcome two independent cohorts, highlighting potential identifying non-responders refractory dexamethasone. Our findings link effects specific immunomodulation dysregulation, highlight omics monitoring vivo target engagement immunomodulatory drugs patient stratification precision medicine approaches.

Language: Английский

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Update der S3-Leitlinie: Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie

Pneumologie, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Zusammenfassung Hintergrund Die nosokomiale Pneumonie, die sowohl im Krankenhaus erworbene (HAP) als auch beatmungsassoziierte Pneumonie (VAP) umfasst, ist nach wie vor eine Hauptursache für Morbidität und Mortalität bei hospitalisierten Erwachsenen. Bei sich verändernden Erregerprofilen aufkommenden Resistenzmustern bietet vorliegende aktualisierte S3-Leitlinie (AWMF-Register-Nr. 020-013) evidenzbasierte Empfehlung zur Verbesserung der Diagnose, Risikostratifizierung Behandlung nosokomialen Pneumonie. Methoden Aktualisierung Leitlinie wurde von einem multidisziplinären Gremium entwickelt, in dem wichtigsten deutschen Fachgesellschaften vertreten waren. Es systematische Literaturrecherche mit anschließender kritischer Bewertung GRADE-Methode durchgeführt. Strukturierte Konsensuskonferenzen stellten sicher, dass Empfehlungen klinisch relevant methodisch fundiert sind den aktuellen Grundsätzen des Antibiotic Stewardship entsprechen. Ergebnisse nosokomialer Pneumonien sollten Patienten solche ohne Risikofaktoren multiresistente Erreger und/oder Pseudomonas aeruginosa unterteilt werden. bakterielle Multiplex-Polymerase-Kettenreaktion (PCR) sollte nicht routinemäßig eingesetzt bronchoskopische Diagnose wird Hinblick auf besser angesehen Probenahme. Eine Antibiotika-Kombinationstherapie septischem Schock hohem Risiko vorbehalten, während anderen einer Monotherapie (z. B. Meropenem) behandelt werden können. stabilisierten Antibiotikatherapie deeskaliert fokussiert sowie Dauer 7–8 Tage verkürzt kritisch kranken prolongierte Applikationsdauer geeigneter Betalaktam-Antibiotika bevorzugt Intensivstation (ICU) besteht das invasiven pulmonalen Aspergillose (IPA). Diagnostik Aspergillus Antigentest aus Bronchiallavageflüssigkeit erfolgen. Schlussfolgerung Diese einen umfassenden, Ansatz Durch Integration neuer diagnostischer Verfahren verfeinerter therapeutischer Strategien zielt sie darauf ab, zu standardisieren, antimikrobielle verbessern, um Auftreten resistenter einzudämmen.

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Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: March 3, 2023

Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism long-term consequences. Even underreporting, an accumulated of almost 650 million people have infected and 620 recovered since start pandemic; therefore, impact these consequences in world population could be significant. Recently, World Health Organization recognized post-COVID syndrome a new entity, guidelines are being established manage treat this condition. However, there still uncertainty about molecular mechanisms behind large number symptoms worldwide. Aims Methods: In study we aimed evaluate clinical lipidomic profiles (using non-targeted lipidomics) patients who had mild severe COVID-19 (acute phase, first epidemic wave); assessment was made two years after initial infection. Results: Fatigue (59%) musculoskeletal (50%) most relevant persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, fatty esters were predicted metabolic pathways affected both post-COVID-19 patients. Principal Component Analysis showed differences between groups. Several species phosphatidylcholines sphingomyelins identified expressed higher levels compared controls. The paired analysis (comparing active 2 recovery) show 170 dysregulated features. relationship such dysregulations symptoms, point importance developing diagnostic therapeuthic markers based on cell signaling pathways.

Language: Английский

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Unintended Consequences: Risk of Opportunistic Infections Associated With Long-term Glucocorticoid Therapies in Adults

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 78(4), P. e37 - e56

Published: Sept. 6, 2023

Abstract Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections widely appreciated. However, the dose-dependent model frequently may not accurately predict risk infection all patients treated with long-term glucocorticoids. In this review, we examine risks opportunistic (OIs) requiring glucocorticoid therapy by evaluating influence dose, duration, potency, combined biological host clinical factors concomitant therapy. We propose strategies prevent OIs, which involve screening, antimicrobial prophylaxis, immunizations. While review focuses on autoimmune, inflammatory, or neoplastic diseases, potential preventative likely applicable other populations. Clinicians should actively assess benefit–harm ratios implement preventive efforts decrease their associated complications.

Language: Английский

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COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 16, 2022

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged twelve COVID-19 patients with Aspergillus fumigatus Rhizopus arrhizus antigens studied the expression activation, maturation, exhaustion markers, well cytokine secretion. Compared healthy controls, T-helper cells displayed increased levels marker PD-1 weakened A. fumigatus- R. arrhizus-induced activation. While baseline secretion proinflammatory cytokines was massively elevated, elicited diminished release T-cellular (e.g., IFN-γ, IL-2) innate immune cell-derived CXCL9, CXCL10) in response antigens. Additionally, samples showed deficient granulocyte activation by mold reduced killing capacity neutrophils. These features anti-mold responses were largely decoupled severity, time elapsed since diagnosis COVID-19, recent corticosteroid uptake, suggesting that impaired defense a common denominator underlying SARS-CoV-2 infection. Taken together, these results expand our understanding predisposition post-viral could inform future studies immunotherapeutic strategies prevent treat superinfections patients.

Language: Английский

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