Search

Although invasive pulmonary aspergillosis (IPA) is typically described in immunocompromised host, patient with severe influenzae can develop IPA. Similarly, patients with severe COVID-19 complicated with IPA are increasingly reported. Here, we describe a case of invasive aspergillosis with triazole-resistant A. fumigatus (TR34/L98H mutation) in a 56-year-old patient with COVID-19 in intensive care unit. This report highlights the need to define the available tools for diagnosis of invasive aspergillosis in severe COVID-19 patients. • Association between COVID-19 and invasive aspergillosis. • Early screening for aspergillosis should be performed in respiratory specimen. • This case emphasizes the need to screen isolates for pan-azole resistance. [ABSTRACT FROM AUTHOR]

Background: Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs).Objective: To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs.Methods: A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed.Results: Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs.Limitations: Due to the retrospective observational design of the study.Conclusions: Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management. [ABSTRACT FROM AUTHOR]

Objectives: Latent infections are well-known for bacteria such as Mycobacterium tuberculosis and for viruses such as Herpesviridae and parasites like Leishmania spp. or Toxoplasma gondii. However, invasive fungi may also be latent and come to reactivate. The aim of this review is to clarify the reactivation concept in major fungal invasive diseases.Method: We have searched for PUBMED publications from 1980 to 2017 with the keywords "fungi", "reactivation", "latency", "dormancy", "granuloma", "Aspergillus", "Mucorales", "Dimorphic fungi", "Histoplasma", "Cryptococcus", "Pneumocystis", "Yeast", "Candida" and "Mold".Results: After primary infection and immune control of the fungus, reactivation can occur following a period of latency. Two conditions must be present: dormancy/survival of the fungi and immunosuppression of the host. Fungal reactivation is easily demonstrated for dimorphic fungi when patients travelling in endemic areas are no longer exposed to fungi at the time they when develop the disease. For cosmopolitan fungi, such as Cryptococcus neoformans, Aspergillus or some emerging fungi, clinical data and animal models have brought some evidence of reactivation. Survival inside macrophages and granuloma formation appear to be predominant conditions to latency. Although granuloma may act as a reservoir for some fungi like Histoplasma or Cryptococcus, its role in mold reactivation has yet to be fully established.Conclusions: The risk of fungal reactivation should be taken into account in patient management, especially in cases of solid organ transplantation or long-term immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Droplet digital PCR (ddPCR) after DNA digestion yielded a 28S rDNA copy number of 61 to 86 copies/genome when testing 10 unrelated Aspergillus fumigatus isolates, higher than with quantitative PCR. Unfortunately, ddPCR after DNA digestion did not improve the sensitivity of our PCR assay when testing serum patients with invasive aspergillosis. [ABSTRACT FROM AUTHOR]

COVID-19-associated mold infections have been increasingly reported, and the main entity is COVID-19-associated aspergillosis (CAPA). Similarly, COVID-19-associated mucormycosis has been reported in hematology, and its prevalence is high and has been increasing in the diabetic population in India during the third COVID-19 pandemic wave. Simultaneous infection with Mucorales and Aspergillus is rare and even rarer during COVID-19. Here, we report the case of a previously immunocompetent patient with severe SARS-CoV-2 infection complicated with probable CAPA and mucormycosis co-infection. Specific diagnostic tools for mucormycosis are lacking, and this case highlights the advantages of analyzing blood and respiratory samples using the quantitative polymerase chain reaction to detect these fungi. We further reviewed the literature on mixed Aspergillus /Mucorales invasive fungal diseases to provide an overview of patients presenting with both fungi and to identify characteristics of this rare infection. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis. [ABSTRACT FROM AUTHOR]

Background Cryptococcosis is an opportunistic infection due to the ubiquitous yeast Cryptococcus neoformans . The pathophysiology of the infection evolves in three steps: primoinfection, dormancy, and reactivation. Dormancy has been evoked based on epidemiological evidence and demonstrated by genotypic data a few years ago. From a biological point of view, little is known about the dormancy itself and on the metabolic state of the yeasts at the single-cell level. Methods Based on CMFDA (glutathione-mediated stress response) and calcofluor (multiplication) stainings, we investigated the metabolism of yeasts (H99 reference strain) using: – our murine model of cryptococcosis (pulmonary resident yeasts 7 days after mouse inoculation); – our model of interaction with murine macrophage (24 hours of internalization). Flow cytometry (MacsQuant analyser) was first used to screen yeasts populations. We confirmed these data using ImageStream X , allowing parallel imaging and cytometry analyses at the single-cell level. We then explored the growth capacities (growth curves) and the transcriptome (real-time quantitative PCR, 37 genes) of the yeasts belonging to different populations after sorting (FacsAria II, BD). Results As soon as thirty hours after inoculation to OF1 outbred mice (MO) and 24 hours of interaction with J774 murine macrophages (MP), we observed the appearance of populations of yeasts with lower CMFDA fluorescence. After sorting yeasts populations (MO and MP) based on the CMFDA fluorescence (CMFDA low, med, high ), we observed that CMFDA low populations were less prone to grow compared to the CMFDA med and CMFDA high populations. The analysis of the transcriptome revealed that MO yeasts activated specific patterns of genes compared to MP yeasts. It also revealed that CMFDA populations had different metabolic characteristics. Finally, 2 genes seemed specifically differentially expressed in the CMFDA low population ( MO and MP ) compared to the other population of yeasts. Conclusion This study provides new data on the physiological adaptation of the yeasts during infection and after macrophage internalization. CMFDA low populations are potentially dormant yeasts and needs to be further explored in terms of cell cycle and basic metabolic activity. [ABSTRACT FROM AUTHOR]

Objectives The increasing reports of outbreaks in renal transplant and pediatric units highlight the need for reliable genotyping methods to characterize nosocomial acquisition of Pneumocystis jirovecii . PCR-based methods, mainly MLST, have been widely used in this setting. Recently, short tandem repeat (STR) typing was suggested to be more sensitive to mixed infection and detect minority genotypes. Till now, no comparison between MLST and STR have been performed. Methods Thirty-seven samples (one per patient) from two hospitals were analysed (Paris hospital, n = 18, Nantes hospital, n = 19). Each sample was analysed by both a STR typing assay using 6 nuclear markers as recently developed with a MLST typing scheme relying on 4 loci (2 nuclear: SOD and ITS1; and 2 mitochondrial genes: mtLSU , Cytb ) as recently proposed. Analyses were performed blindly for the other typing method. Results Thirty-two and 35 different genotypes were observed by MLST and STR typing, respectively. Mixtures of genotypes were detected in 6/37 (16.2%) samples and 20/37 (54.1%) in MLST and STR typing, respectively. One mixed infection out of 6 detected using MLST was not observed using STR typing. Overall, one STR marker tends to differentiate samples between Paris and Nantes hospitals (Chi 2 ; P = 0.003). We then analyzed the 18/37 (48.6%) samples with a unique P. jirovecii genotype. Out of the 18/37 (48.6%) samples with no mixture, 18 and 17 different genotypes were delineated using MLST and STR respectively (one STR genotype was recovered from 2 patients). Conclusion This study provides evidence that STR typing markers compared well to MLST for molecular typing of P. jirovecii from clinical samples. The present STRs is less time-consuming and better discriminated the geographical origin and detection of minority genotypes, which can impact on the interpretation of epidemiological data. [ABSTRACT FROM AUTHOR]

Introduction Nous avons récemment décrit une méthode utilisant la spectrométrie de masse MALDI-TOF pour détecter, identifier et quantifier un disaccharide (MSDS) dont la présence dans le sérum est associée aux infections fongiques invasives (IFI). Nos premières investigations, portant sur des cas de candidoses et d’aspergilloses invasives (IC et IA) recrutés dans notre CHU, ont montré que les performances diagnostiques de cette méthode étaient comparables à celles des tests Platelia™ et Fungitell ® et qu’en outre elle permettait de diagnostiquer les mucormycoses (MM) pour lesquelles ces tests sérologiques sont en défaut. Cette étude a comme objectif de confirmer ces résultats de manière multicentrique. Patients et méthodes Les patients ont été sélectionnés, par divers centres spécialisés dans la prise en charge d’IFI, sur base de la disponibilité de sérums durant des épisodes infectieux documentés. Les patients atteints de CI, provenaient des centres de Gênes et de Rome (26 patients, 57 sérums). Les patients atteints d’AI provenaient de Strasbourg (19 patients, 52 sérums). Les patients atteints de mucormycoses provenaient de deux centres Paris et Dijon (23 patients, 72 sérums). Des témoins hospitalisés présentant les mêmes facteurs de risque que les patients atteints d’IFI ont également été sélectionnés par des centres extérieurs et testés à l’aveugle parallèlement à ces derniers. Il s’agissait de 20 patients neutropéniques (Gênes) et de 20 patients de réanimation ayant présenté une bactériémie (Lausanne). Pour chaque type d’IFI, les tests préconisés pour leur diagnostic visant à détecter le Mannane (Mnn), le Galactomannane (GM), les b-glucanes (BDG) ou la q-PCR ont été réalisés parallèlement à la détection du MSDS. Résultats L’établissement de courbes ROC pour les IC et les IA a permis de définir un cutoff optimal du MSDS à 290 permettant de différencier au mieux les patients atteints d’IFI des témoins. Les résultats correspondants en termes de sensibilité et de spécificité sont résumés dans le tableau ci-dessous par comparaison aux tests de détection des glycannes actuellement disponibles ( Tableau 1 ). Pour les MM, un certain nombre de résultats en cours d’acquisition seront intégrés à notre communication. Il ressort des résultats préliminaires une cinétique de circulation différente de l’ADN et du MSDS. Bien que la sensibilité de ce dernier soit inférieure à celle de la q-PCR, il permet de diagnostiquer isolément des cas de MM et se révèle complémentaire dans l’évolution de leur suivi. Conclusion Cette étude confirme l’intérêt diagnostique du MSDS, sa précocité, sensibilité et sa spécificité sont comparables à celles de tests recommandés par l’EORTC et l’IDSA. Le caractère panfongique du MSDS permet de le proposer en test de dépistage pour les patients à haut risque. Sa contribution au diagnostic apparaît complémentaire de celle des tests actuels dont aucun n’est adapté, à lui seul, à la détection de l’ensemble des IFI. [ABSTRACT FROM AUTHOR]

Contexte Nous avons observés des cas groupés de mucormycoses invasives cutanées à Mucor circinelloides (identification polyphasique avec séquençage des loci ITS, 28S et RPB1) sur une période de 3 ans impliquant 5 patients dans notre centre de traitement des brûlés (hôpital Saint-Louis). À cette occasion, nous avons étudié : – la valeur de la PCR Mucorales dans le plasma pour le diagnostic de mucormycose cutanée ; – avons séquencé le génome complet de 24 souches pour tenter de comprendre la transmission de cette espèce dans le service. Méthodes (i) Soixante-deux prélèvements sanguins réalisés chez 9 patients brûlés hospitalisés dans des centres spécialisés (5 de l’hôpital Percy et 4 de l’hôpital Saint-Louis) ont été rétrospectivement analysés. Six patients ont présenté une mucormycose cutanée invasive prouvée (due à M. circinelloides et Lichtheimia corymbifera ). Trois n’ont présenté qu’une colonisation (une culture positive sur un prélèvement sans caractère invasif) à M. circinelloides et Rhizopus microsporus . (ii) Nous avons sélectionné des isolats cliniques et environnementaux M. circinelloides provenant de 2 hôpitaux (hôpital Percy et hôpital Saint-Louis) et séquencé le génome complet de 24 souches utilisant le NExtSeq 500 (Illumina), réalisé un assemblage de novo et aligné les génomes au génome de référence ( M. circinelloides , F. circinelloides 1006PhL). Résultats (i) Les prélèvements des patients colonisés étaient tous PCR négatifs dans le sérum contrairement aux patients atteint de mucormycose invasive où au moins un prélèvement était PCR positif. La positivité des PCR sériques était toujours antérieure au diagnostic microbiologique (microscopie ou culture) avec une médiane de 4 jours [1–9]. (ii) Un total de 673 000 positions polymorphiques a été observé sur les 24 souches. Les analyses phylogénétiques ont permis de mettre en évidence trois groupes génétiques hautement divergents. Le groupe 3 contenait au moins un isolat des patients concernés par l’épidémie de l’hôpital Saint-Louis et un couple de souches de l’hôpital Percy. Dans chaque hôpital, deux souches identiques ont été isolées de 2 patients différents. Un patient était infecté par 3 souches appartenant au groupe 3 et un patient par 2 souches du groupe 2 et une du groupe 3. Conclusion Cette épidémie a permis de mettre en évidence que : – la PCR Mucorales sur sérum pouvait permettre d’anticiper le diagnostic microbiologique chez les patients brûlés ; – que la transmission de souche ne concernait que 2 sur les 5 patients et que la source probable était probablement composée d’un mélange de plusieurs souches génétiquement distinctes. La source n’a à ce jour toujours pas été mise en évidence. [ABSTRACT FROM AUTHOR]

Objet de l’étude Plusieurs techniques de PCR quantitatives, permettant l’amplification d’ADN spécifiques de certaines espèces fongiques (qPCR spécifiques), ont été développées et évaluées dans le cadre du diagnostic des Aspergilloses et des Mucormycoses. Cependant, au cours de la démarche diagnostique d’une infection fongique invasive (IFI), plusieurs étiologies peuvent être suspectées et l’utilisation d’une PCR pan-fongique, afin d’identifier un plus large panel d’espèces fongiques à partir de prélèvements profonds, apparaît nécessaire. Méthodes Nous avons évalué rétrospectivement la performance d’une puce à ADN pan-fongique, permettant la détection de 25 espèces ou complexes d’espèces fongiques, sur 60 prélèvements profonds congelés (42 biopsies et 18 liquides de ponction), issus de 49 patients chez qui un diagnostic d’IFI avait été documenté. Une PCR (spécifique ou ITS), l’examen direct et/ou la culture étaient positifs dans respectivement 28, 25 et 38 des prélèvements analysés. Pour chacun d’eux, une extraction de l’ADN fongique a été réalisée, puis une cible de l’ADNr a été amplifiée par PCR, enfin les produits de PCR ont été hybridés directement sur la puce. La lecture a été effectuée par un scanner adapté. Résultats obtenus L’hybridation des produits de PCR de 23 biopsies sur 42 (55 %) et de 10 ponctions sur 18 testées (55 %) a permis une identification précise de l’espèce fongique. Le diagnostic étiologique des cas analysés d’Aspergillose, de Candidose, de Cryptococcose, et de Mucormycose a été obtenu respectivement dans 67 % (8/12), 63 % (17/27), 50 % (3/6) et 28 % (4/14). Une infection à Scedosporium prolificans a également été diagnostiquée à partir d’une ponction ganglionnaire. Enfin, cette technique a permis d’identifier la présence de 2 espèces fongiques ( Candida parapsilosis et Aspergillus fumigatus ) au sein d’une même biopsie. Conclusion Cette technique permet la détection dans des prélèvements profonds d’un grand nombre d’espèces fongiques responsables d’IFI selon une procédure rapide et de réalisation facile. Toutefois les performances obtenues pour le diagnostic des infections dues à des Mucorales sont insuffisantes, du fait de l’absence d’hybridation de l’ADN des espèces Lichtheimia ramosa et L. corymbifera . [ABSTRACT FROM AUTHOR]

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified. [ABSTRACT FROM AUTHOR]

To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips. The minimum inhibitory concentrations for amphotericin B, anidulafungin, caspofungin, micafungin, flucytosine, fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole, determined with gradient concentration strips at 35 French microbiology laboratories between 2002 and 2020, were retrospectively collected. Then, the ECVs were calculated using the iterative method and a cut-off value of 97.5%. Minimum inhibitory concentrations were available for 17 653 clinical isolates. In total, 48 ECVs (including 32 new ECVs) were determined: 29 ECVs for frequent yeast species (e.g. Candida albicans and itraconazole/flucytosine, and Candida glabrata species complex [SC] and flucytosine) and rare yeast species (e.g. Candida dubliniensis , Candida inconspicua , Saccharomyces cerevisiae , and Cryptococcus neoformans) and 19 ECVs for Aspergillus flavus SC, Aspergillus fumigatus SC, Aspergillus nidulans SC, Aspergillus niger SC, and Aspergillus terreus SC. These ECVs can be added to the already available gradient concentration strip–specific ECVs to facilitate minimum inhibitory concentration interpretation and streamline the identification of nonwild type isolates. [ABSTRACT FROM AUTHOR]

Background Swine are a major source of meat for humans. As such, they can play an important role in the epidemiology of human toxoplasmosis. Therefore, we performed an epidemiological study to determine the prevalence and genotypes of Toxoplasma gondii in Burkina Fasan swine. Methods The prevalence of T. gondii infection was evaluated in a 3-month prospective study at the slaughterhouse of Bobo-Dioulasso, Burkina Faso. Anti- Toxoplasma IgG titers were determined on meat juices from pig diaphragms using a commercially available ELISA assay. The DNA was extracted from 25 mg of heart biopsies of seropositive animals (IgG ≥ 50% of the control) and the presence of T. gondii DNA was detected using a quantitative PCR assay. Genotyping was performed directly on DNA from PCR-positive biopsies using high-resolution melting and minisequencing analyses of the repeated B1 gene. Results The prevalence of carcasses positive for anti- Toxoplasma IgG was 29% (87/300) with no difference according to sex and age in contrast to the village of origin (p = 0.018). Of the 87 seropositive animals, two were PCR positive (parasitic load at 64 and 128 parasites/mg of heart biopsy). Two new genotypes belonging to Type II and Type III and different from the genotypes previously described using minisequencing were identified. Conclusion Our study provides the first T. gondii seroprevalence data in Burkina Fasan swine. In addition, this direct typing method suggests diversity of the T. gondii genotypes circulating in domestic animals in Burkina Faso. This needs to be confirmed on a wider sampling of subjects. [ABSTRACT FROM AUTHOR]

It is becoming increasingly obvious that glycophosphatidylinositol (GPI)-anchored proteins (GAPs) play a prominent role in fungi, a full understanding of GAPs is however lacking especially for the human opportunistic fungus Cryptococcus neoformans. Using online GPI prediction tools, GAPs were identified and subsequently a mutant library for these GAP-encoding genes was developed and a publicly available knock out (KO) mutant library was used. In total, 41 overexpression and 34 KO mutants, representing 47 unique genes, were analyzed. From the analysis of the two libraries, two main gene candidates, a mannoprotein 88 (MP88) (CNAG_00776) and an uncharacterized protein (CNAG_00137) were further investigated by constructing additional independent mutant strains. The CNAG_00776 mutant showed an impaired growth upon plasma membrane stress and significant decreased phagocytosis. The CNAG_00137 mutant showed impaired growth during cell wall stress or increased temperature and significant decreased phagocytosis. By performing a large genetic screen of GAPs in the genome of the human fungal pathogen C. neoformans , we identified two candidate GAP genes involved in C. neoformans /host interaction and stress response. Further research into these two genes could potentially result in new targets for antfungals, treatment strategies or vaccines to manage C. neoformans disease. [ABSTRACT FROM AUTHOR]

Many factors influence the outcome of in vitro antifungal susceptibility testing (AFST), including endpoint definition, inoculum sizes, time and temperature of incubation, and growth medium used. This European Confederation of Medical Mycology (ECMM) Excellence center driven study investigated multiple colony testing (MCT) of five separate colonies to investigate the prevalence of polyresistance (PR), defined as heterogeneous MICs from a same-species Candida culture irrespective of the underlying resistance mechanism. Candida spp. MCT for fluconazole and anidulafungin was performed by Etest prospectively comprising 405 clinical samples. MCT results were compared to the real-life routine MIC data and PR was assessed. Candida colonies displaying strong PR were selected for genotyping using multilocus sequence typing and random amplified polymorphic DNA assays for C. lusitaniae. Candida PR was observed in 33 of 405 samples (8.1%), with higher rates for non- albicans species (26/186, 14%) than for C. albicans (7/219, 3.2%), and for fluconazole than for anidulafungin. MCT detected acquired resistance more often than routine AFST (18/405, 4.5%) and 9 of the 161 investigated blood cultures showed PR (5.6%). Multilocus sequence typing and random amplified polymorphic DNA did not reveal a uniform genetic correlate in strains studied. This study shows that Candida single MIC-values obtained in routine diagnostics may be incidental, as they fail to detect PR and resistant subpopulations reliably. The reasons for PR seem to be manifold and should be regarded as a phenotypical expression of genomic variability irrespective of the underlying resistance mechanism, which may help to interpret ambiguous and non-reproducible AFST results. [ABSTRACT FROM AUTHOR]

The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis. We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise. Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1–8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01). IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA. [ABSTRACT FROM AUTHOR]