Viral reactivations and fungal infections in nonresolving acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a condition affecting 10% of patients requiring admission to the intensive care unit and results from endothelial dysfunction, alveolar epithelial injury and unbalanced inflammation, leading to exudative pulmonary oedema. A significant portion of these patients experience a lung injury that fails to resolve. Persistent or worsening respiratory failure beyond 5 days after the initiation of mechanical ventilation is referred to as nonresolving ARDS.

The effect of rewarming ischemia on tissue transcriptome and metabolome signatures: A clinical observational study in lung transplantation.

Background: In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction.

Damping excessive viral-induced IFN-γ rescues the impaired anti-Aspergillus host immune response in influenza-associated pulmonary aspergillosis.

Background: Influenza-associated pulmonary aspergillosis (IAPA) is a severe fungal superinfection in critically ill influenza patients that is of incompletely understood pathogenesis. Despite the use of contemporary therapies with antifungal and antivirals, mortality rates remain unacceptably high. We aimed to unravel the IAPA immunopathogenesis as a means to develop adjunctive immunomodulatory therapies.

Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patients.

Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are increasingly recognised as important complications in patients requiring intensive care for severe viral pneumonia. The diagnosis can typically be made in 10-20% of patients with severe influenza or COVID-19, but only when appropriate diagnostic tools are used. Bronchoalveolar lavage sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis, whereas visual examination of the tracheobronchial tract during bronchoscopy is required to detect invasive Aspergillus tracheobronchitis.

Profiling Bacteria in the Lungs of Patients with Severe Influenza Versus COVID-19 with or without Aspergillosis.

The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) has yet to be explored. To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission.

Integrating genetic and immune factors to uncover pathogenetic mechanisms of viral-associated pulmonary aspergillosis.

Invasive pulmonary aspergillosis is a severe fungal infection primarily affecting immunocompromised patients. Individuals with severe viral infections have recently been identified as vulnerable to developing invasive fungal infections. Both influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are linked to high mortality rates, emphasizing the urgent need for an improved understanding of disease pathogenesis to unveil new molecular targets with diagnostic and therapeutic potential.

Lower respiratory tract single-cell RNA sequencing and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis: a single centre, retrospective, observational study.

Background: COVID-19-associated pulmonary aspergillosis (CAPA) is a severe superinfection with the fungus Aspergillus affecting patients who are critically ill with COVID-19. The pathophysiology and the role of neutrophil extracellular traps (NETs) in this infection are largely unknown. We aimed to characterise the immune profile, with a focus on neutrophils and NET concentrations, of critically ill patients with COVID-19, with or without CAPA.

Microbiological Diagnosis of Pulmonary Aspergillus Infections.

As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided.

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

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era.

Methods: We performed a retrospective, monocentric, observational study.

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated. We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 ICU fatalities in a tertiary care center. In this monocentric, descriptive, retrospective case series, we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure who underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021.

Visualising SARS-CoV-2 infection of the lung in deceased COVID-19 patients.

Background: SARS-CoV-2 is a single-stranded positive-sense RNA virus. Several negative-sense SARS-CoV-2 RNA species, both full-length genomic and subgenomic, are produced transiently during viral replication. Methodologies for rigorously characterising cell tropism and visualising ongoing viral replication at single-cell resolution in histological sections are needed to assess the virological and pathological phenotypes of future SARS-CoV-2 variants.

C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions and plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill patients with COVID-19 compared with patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2.

Treatment of Invasive Aspergillosis: How It's Going, Where It's Heading.

Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management.

Successful Multimodal Therapy with Intracerebral Liposomal Amphotericin B and Systemic High-Dose Isavuconazole in Proven Disseminated Aspergillosis.

We report the case of a 32-year-old man receiving chemotherapeutics for an acute B-lymphoblastic leukemia who developed proven cerebral and pulmonary aspergillosis with . Because of progressive fungal disease with neurological deterioration despite adequate systemic antifungal therapy and surgical debridement, intracerebral administration of liposomal amphotericin B was initiated at 5 mg twice weekly. This led to improvement of the cerebral infection.

Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia.

Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study.

Background: Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) affect about 15% of critically ill patients with influenza or COVID-19, respectively. These viral-fungal coinfections are difficult to diagnose and are associated with increased mortality, but data on their pathophysiology are scarce. We aimed to explore the role of lung epithelial and myeloid innate immunity in patients with IAPA or CAPA.

The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution.

Aims: Severe acute respiratory syndrome coronavirus-2 infection causes COVID-19, which in severe cases evokes life-threatening acute respiratory distress syndrome (ARDS). Transcriptome signatures and the functional relevance of non-vascular cell types (e.g.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA).

Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a severe fungal infection complicating critically ill COVID-19 patients. Numerous retrospective and prospective studies have been performed to get a better grasp on this lethal co-infection. We performed a qualitative review and summarized data from 48 studies in which 7047 patients had been included, of whom 820 had CAPA.

Multinational Observational Cohort Study of COVID-19-Associated Pulmonary Aspergillosis.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.