Research

13 pages, 6094 KiB

Open AccessArticle

Experience of Isavuconazole as a Salvage Therapy in Chronic Pulmonary Fungal Disease

by Lisa Nwankwo, Desmond Gilmartin, Sheila Matharu, Ali Nuh, Jackie Donovan, Darius Armstrong-James and Anand Shah

J. Fungi 2022, 8(4), 362; https://doi.org/10.3390/jof8040362 - 31 Mar 2022

Cited by 6 | Viewed by 2161

Abstract

Background: Instances of resistant fungal infection are rising in pulmonary disease, with limited therapeutic options. Therapeutic drug monitoring of azole antifungals has been necessary to ensure safety and efficacy but is considered unnecessary for the newest triazole isavuconazole. Aims: To characterise the prevalence [...] Read more.

Background: Instances of resistant fungal infection are rising in pulmonary disease, with limited therapeutic options. Therapeutic drug monitoring of azole antifungals has been necessary to ensure safety and efficacy but is considered unnecessary for the newest triazole isavuconazole. Aims: To characterise the prevalence of isavuconazole resistance and use in a tertiary respiratory centre. Methods: A retrospective observational analysis (2016–2021) of adult respiratory patients analysing fungal culture, therapeutic drug monitoring, and outcome post-isavuconazole therapy. Results: During the study period, isavuconazole susceptibility testing was performed on 26 Aspergillus spp. isolates. A total of 80.8% of A. fumigatus isolates had isavuconazole (MIC > 1 mg/L, and 73.0% > 2 mg/L) with a good correlation to voriconazole MIC (r = 0.7, p = 0.0002). A total of 54 patients underwent isavuconazole therapy during the study period (median duration 234 days (IQR: 24–499)). A total of 67% of patients tolerated isavuconazole, despite prior azole toxicity in 61.8%, with increased age (r_pb = 0.31; p = 0.021) and male sex (φ_c = 0.30; p = 0.027) being associated with toxicity. A total of 132 isavuconazole levels were performed with 94.8% > 1 mg/L and 72% > 2 mg/L. Dose change from manufacturer’s recommendation was, however, required in 9.3% to achieve a concentration of >2 mg/L. Conclusion: We describe the use of isavuconazole as a salvage therapy in a chronic pulmonary fungal disease setting with a high prevalence of azole resistance. Therapeutic concentrations at standard dosing were high; however, results reinforce antifungal stewardship for optimization. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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19 pages, 3425 KiB

Open AccessArticle

Integration of In Silico and In Vitro Analysis of Gliotoxin Production Reveals a Narrow Range of Producing Fungal Species

by Sergio Redrado, Patricia Esteban, María Pilar Domingo, Concepción Lopez, Antonio Rezusta, Ariel Ramirez-Labrada, Maykel Arias, Julián Pardo and Eva M. Galvez

J. Fungi 2022, 8(4), 361; https://doi.org/10.3390/jof8040361 - 31 Mar 2022

Cited by 2 | Viewed by 1961

Abstract

Gliotoxin is a fungal secondary metabolite with impact on health and agriculture since it might act as virulence factor and contaminate human and animal food. Homologous gliotoxin (GT) gene clusters are spread across a number of fungal species although if they produce GT [...] Read more.

Gliotoxin is a fungal secondary metabolite with impact on health and agriculture since it might act as virulence factor and contaminate human and animal food. Homologous gliotoxin (GT) gene clusters are spread across a number of fungal species although if they produce GT or other related epipolythiodioxopiperazines (ETPs) remains obscure. Using bioinformatic tools, we have identified homologous gli gene clusters similar to the A. fumigatus GT gene cluster in several fungal species. In silico study led to in vitro confirmation of GT and Bisdethiobis(methylthio)gliotoxin (bmGT) production in fungal strain cultures by HPLC detection. Despite we selected most similar homologous gli gene cluster in 20 different species, GT and bmGT were only detected in section Fumigati species and in a Trichoderma virens Q strain. Our results suggest that in silico gli homology analyses in different fungal strains to predict GT production might be only informative when accompanied by analysis about mycotoxin production in cell cultures. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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10 pages, 235 KiB

Open AccessArticle

Characteristics and Outcomes of Patients with Invasive Pulmonary Aspergillosis and Respiratory Tract Aspergillus Colonization from a Tertiary University Hospital in Thailand

by Pannathat Soontrapa, Piriyaporn Chongtrakool and Methee Chayakulkeeree

J. Fungi 2022, 8(4), 344; https://doi.org/10.3390/jof8040344 - 25 Mar 2022

Cited by 2 | Viewed by 1806

Abstract

Positive culture for Aspergillus spp. from respiratory specimens needs to be interpreted together with relevant clinical conditions/settings to differentiate invasive infection from colonization. In this study, we aimed to investigate the association between positive culture for Aspergillus spp. from respiratory specimens and the [...] Read more.

Positive culture for Aspergillus spp. from respiratory specimens needs to be interpreted together with relevant clinical conditions/settings to differentiate invasive infection from colonization. In this study, we aimed to investigate the association between positive culture for Aspergillus spp. from respiratory specimens and the presence of invasive pulmonary aspergillosis. Hospitalized patients with positive culture for Aspergillus spp. from any respiratory sample were retrospectively recruited. Patients were classified into two groups: those with invasive pulmonary aspergillosis and those with non-invasive aspergillosis/colonization. Two hundred and forty-one patients (48.1% male; mean age: 59.8 ± 14.5 years) were included. The most common Aspergillus spp. was A. fumigatus (21.0%). The most common underlying condition was chronic lung disease (23.7%), followed by solid tumor (22.4%). Myeloproliferative disease (aOR: 69.2, 95% CI: 2.4–1991.9), neutropenia ≥ 10 days (aOR: 31.8; 95% CI: 1.10–920.53), and corticosteroid treatment (aOR: 42.8, 95% CI: 6.5–281.3) were independent predictors of the invasive form. Chronic lung disease was independently inversely related to invasive form (OR: 0.04; 95% CI: 0.003–0.49). Serum galactomannan was positive in 69.2% of patients with invasive aspergillosis (OR: 25.9, 95% CI: 5.2–127.8). All inappropriately treated patients with invasive form died. In conclusion, positive culture for Aspergillus spp. from respiratory specimens with coexisting myeloproliferative disease, neutropenia ≥ 10 days, corticosteroid treatment, or positive serum galactomannan is highly suggestive of invasive pulmonary aspergillosis. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

18 pages, 1333 KiB

Open AccessArticle

Routine Surveillance of Healthcare-Associated Infections Misses a Significant Proportion of Invasive Aspergillosis in Patients with Severe COVID-19

by Julia Ebner, Miriam Van den Nest, Lukas Bouvier-Azula, Astrid Füszl, Cornelia Gabler, Birgit Willinger, Magda Diab-Elschahawi and Elisabeth Presterl

J. Fungi 2022, 8(3), 273; https://doi.org/10.3390/jof8030273 - 08 Mar 2022

Cited by 3 | Viewed by 1960

Abstract

Rates of invasive aspergillosis (IA) among COVID-19 ICU patients seem to reach over 30% in certain settings. At Vienna General Hospital (VGH), all rooms in COVID-19 ICUs were put under negative pressure as a protective measure, thus increasing the risk of exposure to [...] Read more.

Rates of invasive aspergillosis (IA) among COVID-19 ICU patients seem to reach over 30% in certain settings. At Vienna General Hospital (VGH), all rooms in COVID-19 ICUs were put under negative pressure as a protective measure, thus increasing the risk of exposure to environmental pathogens for patients. Even though all ICU patients are surveilled for healthcare-associated infections (HAI), there were concerns that the routine protocol might not be sufficient for IA detection. We reviewed the electronic patient charts of all patients with COVID-19 admitted to ICUs between 1 March 2020 and 31 July 2021 for fungal co- or superinfections, comparing four diagnostic algorithms based on different recommendations for the diagnosis of IA (according to EORTC/MSG, BM-AspICU, IAPA and CAPA) to our routine surveillance protocol. We found that out of 252 patients who were admitted to the ICU during the study period, 25 (9.9%) fulfilled the criteria of probable or possible IA of at least one algorithm. The IAPA definitions detected 25 and the CAPA definition 23 probable and 2 possible cases, out of which only 16 were classified as hospital-acquired IA by routine surveillance. In conclusion, adjustment of the routine protocol using a classification system especially designed for respiratory viral illness seems useful for the surveillance of IA in a highly vulnerable patient cohort. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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9 pages, 1816 KiB

Open AccessArticle

A Clustered Case Series of Mucorales Detection in Respiratory Samples from COVID-19 Patients in Intensive Care, France, August to September 2021

by Emilie Guemas, Sophie Cassaing, Sandra Malavaud, Judith Fillaux, Pamela Chauvin, Lucie Lelièvre, Stéphanie Ruiz, Béatrice Riu, Antoine Berry and Xavier Iriart

J. Fungi 2022, 8(3), 258; https://doi.org/10.3390/jof8030258 - 03 Mar 2022

Cited by 10 | Viewed by 1983

Abstract

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) [...] Read more.

While COVID-19-associated pulmonary aspergillosis is now well described in developed countries, COVID-19-associated mucormycosis (CAM) has seemed to remain quite rare in Europe. A retrospective study was performed between March 2020 to September 2021 among COVID-19 adult patients in the intensive care unit (ICU) at Toulouse Hospital (Southern France). PCR screening on respiratory samples, which target Aspergillus or Mucorales DNA, were performed, and the number of fungal detections was evaluated monthly during the study period. During the 19 months of the study, 44 (20.3%) COVID-19 ICU patients had a positive PCR for Aspergillus, an overall rate in keeping with the incidence of ICU COVID-19 patients. Ten patients (7.1%) had a positive Mucorales PCR over the same period. Surprisingly, 9/10 had a positive Mucor/Rhizopus PCR in August-September 2021, during the fourth Delta SARS-CoV-2 variant wave. Epidemic investigations have identified a probable environmental cause linked to construction works in the vicinity of the ICU (high levels of airborne spores due to the mistaken interruption of preventive humidification and summer temperature). Even if CAM are apparently rare in Europe, a cluster can also develop in industrialised countries when environmental conditions (especially during construction work) are associated with a high number of COVID-19 patients in the ICU. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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15 pages, 1331 KiB

Open AccessArticle

Prognostic Scores and Azole-Resistant Aspergillus fumigatus in Invasive Aspergillosis from an Indian Respiratory Medicine ICU (ICU Patients with IA Suspicion)

by Yubhisha Dabas, Anant Mohan and Immaculata Xess

J. Fungi 2021, 7(11), 991; https://doi.org/10.3390/jof7110991 - 20 Nov 2021

Cited by 1 | Viewed by 1653

Abstract

Objective: To assess the effectiveness of three general prognostic models (APACHE II, SAPS II, and SOFA) with serum galactomannan antigen in a clinically suspected invasive aspergillosis (IA) subpopulation admitted to a respiratory medicine ICU and to identify azole-resistant Aspergillus fumigatus (ARAF) cases. Methodology [...] Read more.

Objective: To assess the effectiveness of three general prognostic models (APACHE II, SAPS II, and SOFA) with serum galactomannan antigen in a clinically suspected invasive aspergillosis (IA) subpopulation admitted to a respiratory medicine ICU and to identify azole-resistant Aspergillus fumigatus (ARAF) cases. Methodology and Results: A total of 235 clinically suspected IA patients were prospectively enrolled and observed 30-day mortality was 29.7%. The three general models showed poor discrimination assessed by area under receiver operating characteristic (ROC) curves (AUCs, <0.7) and good calibration (p = 0.92, 0.14, and 0.13 for APACHE II, SAPS II, and SOFA, respectively), evaluated using Hosmer–Lemeshow goodness-of-fit tests. However, discrimination was significantly better with galactomannan values (AUC, 0.924). In-vitro antifungal testing revealed higher minimum inhibitory concentration (MIC) for 12/34 isolates (35.3%) whereas azole resistance was noted in 40% of Aspergillus fumigatus isolates (6/15) with two hotspot cyp51A mutations, G54R and P216L. Conclusions: Patients diagnosed with putative and probable IA (71.4% and 34.6%, respectively), had high mortality. The general prognostic model APACHE II seemed fairly accurate for this subpopulation. However, the use of local GM cut-offs calculated for mortality, may help the intensivists in prompt initiation or change of therapy for better outcome of patients. In addition, the high MICs highlight the need of antifungal surveillance to know the local resistance rate which might aid in patient treatment. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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12 pages, 535 KiB

Open AccessArticle

The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis

by Mahasin Al Shakirchi, Kimmo Sorjonen, Lena Klingspor, Peter Bergman, Lena Hjelte and Isabelle de Monestrol

J. Fungi 2021, 7(11), 944; https://doi.org/10.3390/jof7110944 - 09 Nov 2021

Cited by 5 | Viewed by 1573

Abstract

Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent [...] Read more.

Aspergillus fumigatus is commonly isolated from CF airways. However, the impact on CF lung progression is not completely understood. In this study, using a 16-year retrospective observational cohort study (2000–2015) that included 132 patients, we determined the annual lung function, measured as percent predicted forced expiratory volume in the first second (ppFEV1), decline before and after the first colonization with A. fumigatus. Further, in the same individual, the ratios of lung function when patients were colonized with A. fumigatus and when they were not were calculated. The impact of eradication, with antifungal treatment or spontaneously, was assessed. The annual ppFEV1 was significantly lower after the first colonization with A. fumigatus. Furthermore, within the same individual, colonization with A. fumigatus for two and three years in a row was associated with 4.3% and 7.9% lower ppFEV1, respectively, compared to when not colonized. Finally, patients who eradicated A. fumigatus the following two years after colonization exhibited 9.9% and 14.5% higher ppFEV1 compared to patients who continued to produce cultures with A. fumigatus for two and three years. Our study demonstrated that A. fumigatus colonization was associated with a negative impact on lung function in the long term and eradication, spontaneously or with treatment, was associated with a better pulmonary outcome. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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6 pages, 393 KiB

Open AccessCommunication

COVID-19-Associated Pulmonary Aspergillosis in Patients with Acute Leukemia: A Single-Center Study

by Jovan Rajic, Ivana Gmizic, Tara Gunjak, Violeta Milosevic, Nikola Pantic, Nikica Sabljic, Mirjana Mitrovic, Aleksandra Djuric Stefanovic, Ljubica Lazic, Snezana Jovanovic, Ivana Milošević, Aleksandra Barac and Ana Vidovic

J. Fungi 2021, 7(11), 890; https://doi.org/10.3390/jof7110890 - 21 Oct 2021

Cited by 7 | Viewed by 2278

Abstract

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study [...] Read more.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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14 pages, 880 KiB

Open AccessArticle

Chronic Pulmonary Aspergillosis: Disease Severity Using Image Analysis and Correlation with Systemic Proinflammation and Predictors of Clinical Outcome

by Shiang-Fen Huang, Chia-Chang Huang, Kun-Ta Chou, Yu-Jiun Chan, Ying-Ying Yang and Fu-Der Wang

J. Fungi 2021, 7(10), 842; https://doi.org/10.3390/jof7100842 - 07 Oct 2021

Cited by 5 | Viewed by 1862

Abstract

(1) Background: The presentation of chronic pulmonary aspergillosis (CPA) ranges from single granuloma to fibrosis in the affected lung. CPA can be divided into five categories according to European Respirology Society (ERS) guidance but is usually assessed by clinical physicians. Computer-based quantitative lung [...] Read more.

(1) Background: The presentation of chronic pulmonary aspergillosis (CPA) ranges from single granuloma to fibrosis in the affected lung. CPA can be divided into five categories according to European Respirology Society (ERS) guidance but is usually assessed by clinical physicians. Computer-based quantitative lung parenchyma analysis in CPA and its correlation with clinical manifestations, systemic inflammation, and angiogenesis have never been investigated. (2) Method: Forty-nine patients with CPA and 36 controls were prospectively enrolled. Pulmonary function tests (forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV₁/FCV) and biomarkers in the peripheral blood (the chemokines interleukin (IL)-1B, IL-6, IL-10, IL-8, CRP, ESR, MMP1, MMP7, MMP8, TNF-α, calprotectin, SDF-1α, and VEGFA) were measured before antifungal treatment. The disease severity was categorized into mild, moderate, and severe based on chest computed tomography (CT) images. The oxygen demand and overall mortality until the end of the study were recorded. Quantitative parenchyma analysis was performed using the free software 3Dslicer. (3) Results: The results of quantitative parenchyma analysis concorded with the visual severity from the chest CT, oxygen demand, FVC, and FEV₁ in the study subjects. The decrease in kurtosis and skewness of the lung density histograms on CT, increase in high attenuation area (HAA), and reduced lung volume were significantly correlated with increases in the PMN %, CRP, IL-1B, SDF-1α, MMP1, and Calprotectin in peripheral blood in the multivariable regression analysis. TNF-α and IL-1B at study entry and the CPA severity from either a visual method or computer-based evaluation were predictors of long-term mortality. (4) Conclusion: The computer-based parenchyma analysis in CPA agreed with the categorization on a visual basis and was associated with the clinical outcomes, chemokines, and systemic proinflammation profiles. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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9 pages, 246 KiB

Open AccessArticle

Predictors of Early and Late Mortality for Patients with Hematologic Malignancy and Invasive Mold Disease

by Eva L. Yashphe, Ron Ram, Irit Avivi and Ronen Ben-Ami

J. Fungi 2021, 7(9), 697; https://doi.org/10.3390/jof7090697 - 27 Aug 2021

Cited by 1 | Viewed by 1382

Abstract

Background: Invasive mold infections (IMI) are leading infectious causes of mortality among patients with hematological malignancies. Objectives: To determine the relative contribution of host, disease, and treatment-related factors to patient survival. Methods: An observational, retrospective cohort study reviewing the medical records of patients [...] Read more.

Background: Invasive mold infections (IMI) are leading infectious causes of mortality among patients with hematological malignancies. Objectives: To determine the relative contribution of host, disease, and treatment-related factors to patient survival. Methods: An observational, retrospective cohort study reviewing the medical records of patients with hematological malignancy and IMI (2006–2016). Causes of death were classified up to 90 days after diagnosis. Kaplan–Meier and Cox regression analyses were used to determine risk factors for early, late, and overall mortality. Results: Eighty-six patients with IMI were included; 29 (34%) and 41 (47%) died within 6 and 12 weeks of diagnosis, respectively. Death was attributed to IMI in 22 (53.6%) patients, all of whom died within 45 days of diagnosis. Risk factors for early mortality were elevated serum galactomannan, treatment with amphotericin B, IMI progression 3 weeks after diagnosis, and lymphoma undergoing HCT. Late mortality was associated with relapsed/refractory malignancy and elevated serum galactomannan. Conclusions: In this single-center study of patients with IMI, infections were the most frequent causes of death, and time-dependent risk factors for death were identified. These results may help direct risk-assessment and monitoring of patients undergoing treatment of IMI. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

13 pages, 1413 KiB

Open AccessArticle

Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis: Multicenter Prospective Cohort Study

by Meng-Rui Lee, Hung-Ling Huang, Li-Ta Keng, Hsu-Liang Chang, Chau-Chyun Sheu, Pin-Kuei Fu, Jann-Yuan Wang, Inn-Wen Chong, Jin-Yuan Shih and Chong-Jen Yu

J. Fungi 2021, 7(6), 480; https://doi.org/10.3390/jof7060480 - 12 Jun 2021

Cited by 6 | Viewed by 3092

Abstract

Objectives: Aspergillus-specific IgG (Asp-IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus-specific IgG [...] Read more.

Objectives: Aspergillus-specific IgG (Asp-IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus-specific IgG (Asp-IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden’s index and validated. Results: A total of 373 participants were recruited. In the derivation cohort (n = 262), Asp-IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort (n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort. Conclusions: Serum Asp-IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L). Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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11 pages, 1445 KiB

Open AccessArticle

Detection of Candida albicans-Specific CD4+ and CD8+ T Cells in the Blood and Nasal Mucosa of Patients with Chronic Rhinosinusitis

by Pascal Ickrath, Lisa Sprügel, Niklas Beyersdorf, Agmal Scherzad, Rudolf Hagen and Stephan Hackenberg

J. Fungi 2021, 7(6), 403; https://doi.org/10.3390/jof7060403 - 21 May 2021

Cited by 2 | Viewed by 1833

Abstract

Candida albicans is ubiquitously present, and colonization in the nose and oral cavity is common. In healthy patients, it usually does not act as a pathogen, but in some cases can cause diseases. The influence of C. albicans as a trigger of T [...] Read more.

Candida albicans is ubiquitously present, and colonization in the nose and oral cavity is common. In healthy patients, it usually does not act as a pathogen, but in some cases can cause diseases. The influence of C. albicans as a trigger of T cell activation on the pathogenesis of chronic rhinosinusitis (CRS) is controversial, and its exact role is not clear to date. The aim of the present study was to detect and characterize C. albicans-specific CD4+ and CD8+ T cells in patients with CRS, with and without nasal polyps. Tissue and blood samples were collected from patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP), and from healthy controls. A peptide pool derived from C. albicans antigen was added to tissue and blood samples. After 6 days, lymphocytes were analyzed by multicolor flow cytometry. Activation was assessed by the intracellular marker Ki-67, and the cytokine secretion was measured. Tissue CD8+ T cells of CRSsNP patients showed a significantly higher proportion of Ki-67+ cells after activation with C. albicans antigen compared to peripheral blood CD8+ T cells. Cytokine secretion in response to C. albicans antigen was similar for all study groups. In this study, C. albicans-specific CD4+ and CD8+ T cells were detected in peripheral blood and mucosal tissue in all study groups. In patients suffering from CRSsNP, C. albicans-specific CD8+ T cells were relatively enriched in the nasal mucosa, suggesting that they might play a role in the pathogenesis of CRSsNP. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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Review

Jump to: Research, Other

13 pages, 972 KiB

Open AccessReview

Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections

by Bianca C. S. C. Barros, Bruna R. Almeida, Debora T. L. Barros, Marcos S. Toledo and Erika Suzuki

J. Fungi 2022, 8(6), 548; https://doi.org/10.3390/jof8060548 - 24 May 2022

Cited by 4 | Viewed by 2804

Abstract

The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell [...] Read more.

The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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17 pages, 500 KiB

Open AccessReview

Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients

by Francesca Raffaelli, Eloisa Sofia Tanzarella, Gennaro De Pascale and Mario Tumbarello

J. Fungi 2022, 8(4), 415; https://doi.org/10.3390/jof8040415 - 17 Apr 2022

Cited by 9 | Viewed by 3432

Abstract

Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly [...] Read more.

Patients with coronavirus disease 19 (COVID-19) admitted to the intensive care unit (ICU) often develop respiratory fungal infections. The most frequent diseases are the COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated pulmonary mucormycosis (CAPM) and the Pneumocystis jirovecii pneumonia (PCP), the latter mostly found in patients with both COVID-19 and underlying HIV infection. Furthermore, co-infections due to less common mold pathogens have been also described. Respiratory fungal infections in critically ill patients are promoted by multiple risk factors, including epithelial damage caused by COVID-19 infection, mechanical ventilation and immunosuppression, mainly induced by corticosteroids and immunomodulators. In COVID-19 patients, a correct discrimination between fungal colonization and infection is challenging, further hampered by sampling difficulties and by the low reliability of diagnostic approaches, frequently needing an integration of clinical, radiological and microbiological features. Several antifungal drugs are currently available, but the development of new molecules with reduced toxicity, less drug-interactions and potentially active on difficult to treat strains, is highly warranted. Finally, the role of prophylaxis in certain COVID-19 populations is still controversial and must be further investigated. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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Other

Jump to: Research, Review

6 pages, 689 KiB

Open AccessCase Report

A Clinical Case of COVID-19-Associated Pulmonary Aspergillosis (CAPA), Illustrating the Challenges in Diagnosis (Despite Overwhelming Mycological Evidence)

by P. Lewis White, Jan Springer, Matt P. Wise, Hermann Einsele, Claudia Löffler, Michelle Seif, Sabrina Prommersberger, Matthijs Backx and Jürgen Löffler

J. Fungi 2022, 8(1), 81; https://doi.org/10.3390/jof8010081 - 14 Jan 2022

Cited by 5 | Viewed by 2003

Abstract

The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential [...] Read more.

The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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11 pages, 1818 KiB

Open AccessCase Report

Mixed Etiology COVID-19 Associated Pulmonary Aspergillosis (CAPA)—A Case Report and Brief Review of the Literature

by Dan Alexandru Toc, Carmen Costache, Alexandru Botan, Razvan Marian Mihaila, Ioana Alina Colosi, Sandor Botond Buksa and Roxana Mihaela Chiorescu

J. Fungi 2021, 7(10), 877; https://doi.org/10.3390/jof7100877 - 18 Oct 2021

Cited by 10 | Viewed by 2867

Abstract

The SARS-CoV-2 pandemic has proved to be a significant risk addition for invasive infections with Aspergillus. Even though there are plenty of data about the COVID-19-associated pulmonary aspergillosis (CAPA), especially involving Aspergillus fumigatus, recent studies are presenting cases of CAPA involving more [...] Read more.

The SARS-CoV-2 pandemic has proved to be a significant risk addition for invasive infections with Aspergillus. Even though there are plenty of data about the COVID-19-associated pulmonary aspergillosis (CAPA), especially involving Aspergillus fumigatus, recent studies are presenting cases of CAPA involving more than one species of Aspergillus. We report the first case of a SARS-CoV-2 patient associating co-infection with, most likely, Aspergillus section Fumigati and Aspergillus section Flavi from Romania, and we review the existing medical literature in order to shed light upon mixed etiology cases of CAPA. Since mortality remains high in these cases, there is an acute need for more information about the interaction between SARS-CoV-2 and Aspergillus spp., and the therapies for CAPA. The emerging number of cases and the high mortality rate must be considered an incentive for future research. Full article

(This article belongs to the Special Issue Respiratory Fungal Infections)

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