Invasive pulmonary aspergillosis (IPA) is a very severe manifestation of Aspergillus disease. Besides well-known risk groups of deeply neutropenic hematologic and solid organ transplant recipients other risk groups among patients treated in ICUs have been recognized. The prevalence of IPA among ICU-patients is not known and it is not known how well IPA is recognized in ICU-settings. The diagnosis of IPA is often difficult to make and non-invasive ways to diagnose IPA reliably are needed. Objectives: In this study we studied the clinical significance of Aspergillus-positive respiratory samples in ICU-patients. Methods: We retrospectively evaluated the ICU-patients (N = 205) who provided Aspergillus-positive respiratory samples in 2007-2020 and classified patients to groups of "colonization", "putative IPA", "proven IPA ", as in AspICU algorithm. Data were collected from laboratory registry and Helsinki University Hospital medical records. Underlying conditions, reasons leading to treatment in ICU, immunosuppression, known risk factors of IA in ICU, signs of infection, results of Aspergillus-specific laboratory testing, use of antifungal treatment, survival, and reason of death were assessed. Results: Majority of the findings (63%) were colonization, 11 (5%) patients had proven IPA, and "putative IPA" 59 (29%) of the patients. All patients with proven IPA died within one year, whereas mortality in putative and colonization groups was 39% and 33% respectively. Difference in mortality during one year between "colonization" and "putative IPA" groups was not statistically significant (p = .244), but when both "proven" and "putative" IPA were included, the difference was statistically significant, p = .019. Overall hospital mortality in the study group was 38%. Mortality in all the groups is higher than overall ICU-patient mortality of non-selected patients in Finland. Conclusions: The overall incidence of Aspergillus-findings in our ICUs was low. Isolation of Aspergillus in critically ill is associated with high mortality irrespective of invasion or colonization.

The incidence rate of COVID-19-associated pulmonary aspergillosis (CAPA) is rising. However, the pathogenesis of CAPA remains unclear. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection disrupts pathways related to type I interferon and Toll-like receptors, key components in innate immunity, thereby elevating the incidence of CAPA. Additionally, SARS-CoV-2 infection results in T and B cell functional deficiencies or exhaustion within adaptive immunity, weakening the defense against invasive Aspergillus. Furthermore, SARS-CoV-2 infection enhances the replication of cytomegalovirus and alters the gut microbiota, factors that may aid in diagnosing CAPA. Immunosuppressive therapy in COVID-19 patients is also believed to heighten the risk of invasive aspergillosis. Therefore, this review, examines the immune response to SARS-CoV-2 infection combined with invasive aspergillosis, and explores the pathogenesis and susceptibility factors of CAPA. We propose that variations in an individual's immune response significantly determine susceptibility to CAPA. The aim of this paper is to deepen clinical understanding of CAPA's pathogenesis, thereby aiding in mitigating susceptibility risk and advancing novel treatment approaches.

Mucorales polymerase chain reaction (PCR) is used to diagnose pulmonary mucormycosis (PM) among neutropenic individuals. However, data on the utility of PCR in patients with diabetes mellitus, another major risk factor for PM, are limited.

The primary objective was to assess the diagnostic performance of a commercial real-time PCR assay (MucorGenius) in plasma and bronchoalveolar lavage fluid (BALF) for diagnosing PM (proven and probable cases only) in patients with suspected invasive mould disease (IMD). For the secondary objective, we evaluated the performance of the MucorGenius assay in all PM (proven, probable, and possible) cases.

We prospectively enrolled patients with suspected IMD and assessed the performance of MucorGenius PCR (index test) in plasma and BALF samples. A multidisciplinary team assigned the final diagnosis of IMD (reference standard) based on microscopy, histopathology, cytology, and culture. We report the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals (CI).

We enrolled 103 patients, of whom 43 (41.7%) were confirmed to have PM. Plasma PCR showed a sensitivity of 18.6% (95% CI: 8.4-33.4), specificity of 90.7% (95% CI:77.9-97.4), PPV of 66.7%, and NPV of 52.7%. Including possible PM/IMD cases improved the plasma PCR sensitivity to 30.0% (95% CI: 18.9-43.2) and retained specificity at 90.7%. BALF PCR had better sensitivity (47.4%) but poorer specificity (69.6%), with a PPV of 56.3% and NPV of 61.5%.

Plasma and BALF MucorGenius PCR have poor diagnostic performance for diagnosing PM among individuals with diabetes mellitus. Further multicenter studies are needed to validate these findings.

Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients and incidences vary in the literature. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker, although the optimal cutoff is unclear.

This was a single-center cohort study of patients requiring mechanical ventilation in the medical intensive care unit (ICU) from June 2018 to March 2023. Demographics, BAL, and outcome data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus from BAL, those who had elevated BAL GM levels (>0.5, >0.8, or >1.0) but did not grow Aspergillus, and those with neither.

Of >1700 BALs from 688 patients, only 18 BALs from 15 patients grew Aspergillus. Patients who grew Aspergillus had more intubated days (29 vs 11, P = .002) and more ICU days (34 vs 15, P = .002). BAL GM level was higher from samples that grew Aspergillus than those that did not (median optical density index: 7.08 vs 0.11, P < .001).

In this large cohort of critically ill patients, we found a low rate of Aspergillus growth and variable BAL GM elevation. These data suggest that the pretest probability of IPA should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Elevated BAL GM may not reliably indicate invasive disease, but lack of culture positivity may also miss true infection. Improved scoring systems are needed to enhance pretest probability for diagnostic test stewardship purposes, and tests must be interpreted in their own clinical contexts.

Although coronavirus disease 2019 (COVID-19) is no longer classified as a Public Health Emergency of International Concern by World Health Organization, its global impact persists. Data on its impact in lung transplant recipients (LTRs) from China remain limited. This study aims to share clinical experiences and provide insights into managing LTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

We conducted a study on LTRs with COVID-19 caused by the Omicron variant from November 17, 2022, to May 1, 2023. Clinical information was gathered retrospectively through electronic medical records, questionnaires, or follow-up telephone calls.

A total of 227 LTRs were reviewed for infection with Omicron variant. After excluding 49 cases without confirmed SARS-CoV-2 infection, this left a final cohort of 178 infected LTRs, accounting for an infection rate of 78.4% (178/227). Of the patients, 50% (89/178) required hospitalization, with an average hospital stay of 16 days [interquartile range (IQR): 9.5-25.5 days]. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the severe/critical group (S/C group), while the remaining 58.4% (52/89) had mild or moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher C-reactive protein (CRP) (59.6 vs. 16.8 mg/L, P<0.001), Erythrocyte sedimentation rate (45.5 vs. 22.5 mm/h, P=0.005) and D-dimer level (1.09 vs. 0.65 mg/L, P=0.01), but lower CD4+ T lymphocytes count (217 vs. 427 cells/µL, P=0.004). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P=0.006) and pulmonary fungal infection (73.0% vs. 38.5%, P=0.001) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8 mg/L), combined pulmonary fungal infection, and interstitial lung disease (ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective odds ORs values of 4.23 [95% confidence interval (CI): 1.68-11.23], 4.76 (95% CI: 1.59-15.64), and 5.13 (95% CI: 1.19-29.17). Receiver operating characteristic (ROC) curve analysis showed that CD4+ T lymphocyte count may be a strong marker for predicting death. At a cutoff of 404 cells/µL, sensitivity was 0.509, specificity 0.999, and area under the curve (AUC) was 0.806 (95% CI: 0.678-0.934). Ultimately, 13 recipients succumbed to COVID-19 related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 7.3% (13/178).

LTRs are at high risk of secondary lung infections after Omicron. Key risk factors for severe disease include CRP >41.8 mg/L, ILD as primary disease, and pulmonary fungal infection. CD4+ T lymphocyte count may predict mortality risk in LTRs with COVID-19.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is an established support option for patients with very severe respiratory failure and played an important role during the coronavirus disease 2019 (COVID-19) pandemic. Bacteria and fungi can lead to severe infectious complications in critically ill patients. The aim of this study was to describe the microbiological spectrum of bacteria and fungi detected in patients with COVID-19-associated respiratory failure supported with VV ECMO in our center.

This retrospective single-center analysis included all patients with COVID-19-associated respiratory failure supported with VV ECMO in our center between March 2020 and May 2022. All findings from microbiological samples, taken as part of clinical routine assessment from initiation of VV ECMO until day 30 were included. Samples were described by site and time of detection and microbiological characteristics.

From March 2020 through May 2022, 88 patients with COVID-19-associated respiratory failure received VV ECMO support at our center. In 83/88 patients (94.3%), one or more pathogens were found in microbiological samples. Most pathogens were isolated from samples from the respiratory tract (88.6%). Earliest detection occurred in samples from the respiratory tract with a median time of 5 days to first detection. The most frequently detected pathogens were Staphylococcus spp., Candida spp., Klebsiella spp., Escherichia coli and Enterococcus spp.

In this cohort of severely ill COVID-19 patients receiving VV ECMO support, pathogens were frequently detected.

In the intensive care unit (ICU), invasive aspergillosis (IA) has a poor prognosis. Some studies report a positive association between diabetes mellitus (DM) and IA in critically ill patients, but the relationship between DM and IA in the ICU remains controversial. We aimed to clarify the relationship between DM and IA among patients in the ICU in a systematic review and meta-analysis.

We retrieved all reports published in PubMed, EMBASE, and the Cochrane Library databases before July 12, 2023. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the relationship between DM and IA. Subgroup analyses were conducted to further analyze sources of heterogeneity. Heterogeneity was evaluated using the Cochran's Q test and I2 statistic. Additionally, we evaluated publication bias using funnel plots, Egger's test, and Begg's test. Finally, sensitivity analysis was conducted to evaluate the robustness of the results.

Twenty studies with 6155 participants were included in this meta-analysis. We found a positive association between DM and IA among patients in the ICU (OR = 1.18, 95% CI:1.01 to 1.39; p = 0.04). The heterogeneity was not significant (I² = 5%; p = 0.39) and publication bias was not significant (Egger's test: p = 0.654; Begg's test: p = 0.417). The results of sensitivity analysis supported a stable association between DM and IA. Subgroup analysis indicated that patients' comorbidities might be a potential source of heterogeneity. Additionally, patients with DM had a significantly higher risk of COVID-19-associated pulmonary aspergillosis (CAPA) than those without DM (OR = 1.40, 95% CI: 1.15 to 1.70; p < 0.001). The heterogeneity was not significant (I² = 0%; p = 0.91). In the subgroup with influenza, the OR of the relationship between DM and IA was 0.81 (95% CI: 0.54, 1.23; p = 0.32; heterogeneity: p = 0.36; I² = 8%).

Patients with DM in the ICU showed a higher risk of developing IA than patients in the ICU without DM. DM was a significant risk factor for IA, with the highest risk observed in critically ill patients diagnosed with CAPA.

The rising incidence of fungal infections coupled with limited treatment options underscores the urgent need for novel antifungal therapies. Riboswitches, particularly thiamin pyrophosphate (TPP) class, have emerged as promising antimicrobial targets. This study presents a comprehensive genome-wide analysis of TPP riboswitches in 156 medically relevant fungi utilizing advanced covariance models (CMs) tailored for fungal sequences. Our investigation identified 378 conserved TPP riboswitch sequences distributed across 140 distinct species, revealing a broader prevalence than that previously recognized. Notably, we provide evidence for a novel putative group of TPP riboswitches, designated TPPswSUGAR, associated with sugar transporters in Mucoromycota and Basidiomycota. This group exhibits distinctive structural features while maintaining key TPP-binding motifs, potentially expanding our understanding of the riboswitch diversity in fungi. Our analysis highlights the impact of P3 stem variability on riboswitch detection and characterization, demonstrating the superiority of fungal-specific CMs over generic models. We observed multiple TPP riboswitches in over 50% of the examined species, including clinically significant pathogens involved in aspergillosis and mucormycosis. Remarkably, Aspergillus latus, a species associated with COVID-19 coinfections, harbors six distinct TPP riboswitch sequences, whereas the extremophilic black fungus Hortaea werneckii possesses nine. These findings not only elucidate the diverse distribution of TPP riboswitches in pathogenic fungi but also emphasize their potential as multifaceted targets for antifungal drug development. By addressing key limitations of previous detection methods and providing insights into riboswitch structural diversity, this study lays a foundation for future investigations into riboswitch-mediated regulation in fungi and the development of novel antifungal strategies.

To assess the prevalence and relevance of invasive fungal disease (IFD) during veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO).

Retrospective analysis from January 2013 to November 2023 of adult V-A ECMO cases at a German University Hospital. Parameters relating to IFD, demographics, length of stay (LoS), days on ECMO and mechanical ventilation, prognostic scores and survival were assessed. Multivariable logistic regression analyses with IFD and death as dependent variables were performed. Outcome was assessed after propensity score matching IFD-patients to non-IFD-controls.

421 patients received V-A ECMO. 392 patients with full electronic datasets were included. The prevalence of IFD, invasive candidiasis and probable invasive pulmonary aspergillosis was 4.6%, 3.8% and 1.0%. Severity of acute disease, pre-existing moderate-to-severe renal disease and continuous kidney replacement therapy were predictive of IFD. In-hospital mortality (94% (17/18) compared to 67% (252/374) in non-IFD patients (p = 0.0156)) was predicted by female sex, SOFA score at admission, SAVE score and IFD (for IFD: OR: 8.31; CI: 1.60-153.18; p: 0.044). There was no difference in outcome after matching IFD-cases to non-IFD-controls.

IFD are detected in about one in 20 patients on V-A ECMO, indicating mortality >90%. However, IFD do not contribute to prognosis in this population.

The coronavirus disease 2019 (COVID-19) pandemic was a cataclysmic event that infected over 772 million and killed over 6.9 million people worldwide. The pandemic pushed hospitals and society to their limits and resulted in incredibly severe respiratory disease in millions of people. This severe respiratory disease often necessitated maximum medical therapy, including the use of extracorporeal membrane oxygenation. While our understanding of COVID-19 and its treatment continue to evolve, we review the current evidence to guide the care of patients with severe COVID-19 infection.

Due to the limitations of traditional laboratory methods (TMs), identification of causative pathogens of numerous pulmonary infections (PIs) remains difficult. This study evaluated the value of metagenomic next generation sequencing (mNGS) in the identification of various respiratory pathogens. A total of 207 patients with TMs and mNGS data were collected for this retrospective study. TMs included sputum culture, blood, and bronchoalveolar lavage fluid (BALF) analysis, or polymerase chain reaction analysis of throat swabs. Otherwise, BALF was collected and analyzed using mNGS. For bacterial pathogens, sensitivities of mNGS as compared to TMs were 76.74 % and 58.14 % (P=0.012). For fungal pathogens, the detection rate of mNGS sensitivity was higher as compared to that of TMs (93.68 % vs 22.11 %; P<0.001). The positive predictive value and negative predictive value were also greater for mNGS. Use of mNGS for BALF analysis offers good specificity and thus facilitates to the clinical diagnosis of PIs.

In a retrospective view, this review examines the impact of mucormycosis on health workers and researchers during the COVID era. The diagnostic and treatment challenges arising from unestablished underlying pathology and limited case studies add strain to healthcare systems. Mucormycosis, caused by environmental molds, poses a significant threat to COVID-19 patients, particularly those with comorbidities and compromised immune systems. Due to a variety of infectious Mucorales causes and regionally related risk factors, the disease's incidence is rising globally. Data on mucormycosis remains scarce in many countries, highlighting the urgent need for more extensive research on its epidemiology and prevalence. This review explores the associations between COVID-19 disease and mucormycosis pathology, shedding light on potential future diagnostic techniques based on the fungal agent's biochemical components. Medications used in ICUs and for life support in ventilated patients have been reported, revealing the challenge of managing this dual onslaught. To develop more effective treatment strategies, it is crucial to identify novel pharmacological targets through "pragmatic" multicenter trials and registries. In the absence of positive mycology culture data, early clinical detection, prompt treatment, and tissue biopsy are essential to confirm the specific morphologic features of the fungal agent. This review delves into the history, pathogens, and pathogenesis of mucormycosis, its opportunistic nature in COVID or immunocompromised individuals, and the latest advancements in therapeutics. Additionally, it offers a forward-looking perspective on potential pharmacological targets for future drug development.

Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest.

This study aimed to provide evidence for the early warning and management of fungal infections.

We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed.

A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy.

The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for CAPA have not been systematically addressed to date.

In this systematic review and meta-analysis to identify factors associated with CAPA, we comprehensively searched five medical databases: Ovid MEDLINE; Ovid Embase; the Cochrane Database of Systematic Reviews; the Cochrane Central Register of Controlled Trials; and the WHO COVID-19 Database. All case-control and cohort studies in adults (aged >18 years) that described at least six cases of CAPA and evaluated any risk factors for CAPA, published from Dec 1, 2019, to July 27, 2023, were screened and assessed for inclusion. Only studies with a control population of COVID-19-positive individuals without aspergillosis were included. Two reviewers independently screened search results and extracted outcome data as summary estimates from eligible studies. The primary outcome was to identify the factors associated with CAPA. Meta-analysis was done with random-effects models, with use of the Mantel-Haenszel method to assess dichotomous outcomes as potential risk factors, or the inverse variance method to assess continuous variables for potential association with CAPA. Publication bias was assessed with funnel plots for factors associated with CAPA. The study is registered with PROSPERO, CRD42022334405.

Of 3561 records identified, 27 articles were included in the meta-analysis. 6848 patients with COVID-19 were included, of whom 1324 (19·3%) were diagnosed with CAPA. Diagnosis rates of CAPA ranged from 2·5% (14 of 566 patients) to 47·2% (58 of 123). We identified eight risk factors for CAPA. These factors included pre-existing comorbidities of chronic liver disease (odds ratio [OR] 2·70 [95% CI 1·21-6·04], p=0·02; I2=53%), haematological malignancies (OR 2·47 [1·27-4·83], p=0·008; I2=50%), chronic obstructive pulmonary disease (OR 2·00 [1·42-2·83], p<0·0001; I2=26%), and cerebrovascular disease (OR 1·31 [1·01-1·71], p=0·05; I2=46%). Use of invasive mechanical ventilation (OR 2·83; 95% CI 1·88-4·24; p<0·0001; I2=69%), use of renal replacement therapy (OR 2·26 [1·76-2·90], p<0·0001; I2=14%), treatment of COVID-19 with interleukin-6 inhibitors (OR 2·88 [1·52-5·43], p=0·001; I2=89%), and treatment of COVID-19 with corticosteroids (OR 1·88 [1·28-2·77], p=0·001; I2=66%) were also associated with CAPA. Patients with CAPA were typically older than those without CAPA (mean age 66·6 years [SD 3·6] vs 63·5 years [5·3]; mean difference 2·90 [1·48-4·33], p<0·0001; I2=86%). The duration of mechanical ventilation in patients with CAPA was longer than in those without CAPA (n=7 studies; mean duration 19·3 days [8·9] vs 13·5 days [6·8]; mean difference 5·53 days [1·30-9·77], p=0·01; I2=88%). In post-hoc analysis, patients with CAPA had higher all-cause mortality than those without CAPA (n=20 studies; OR 2·65 [2·04-3·45], p<0·0001; I2=51%).

The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19.

None.

Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness.

A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection.

The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05).

The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

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.

We performed a retrospective, monocentric, observational study. We collected data from adult patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit (ICU) of University Hospitals Leuven, a tertiary referral center, between 1 March 2020 and 14 November 2022. Probable or proven CAPA was diagnosed according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) criteria.

We included 335 patients. Bronchoalveolar lavage sampling was performed in 300 (90%), and CAPA was diagnosed in 112 (33%). The incidence of CAPA was 62% (50 of 81 patients) in European Organisation for Research and Treatment of Cancer (EORTC)/Mycosis Study Group Education and Research Consortium (MSGERC) host factor-positive patients, compared with 24% (62 of 254) in host factor-negative patients. The incidence of CAPA was significantly higher in the vaccination era, increasing from 24% (57 of 241) in patients admitted to the ICU before October 2021 to 59% (55 of 94) in those admitted since then. Both EORTC/MSGERC host factors and ICU admission in the vaccination era were independently associated with CAPA development. CAPA remained an independent risk factor associated with mortality risk during the vaccination era.

The presence of EORTC/MSGERC host factors for invasive mold disease is associated with increased CAPA incidence and worse outcome parameters, and it is the main driver for the significantly higher incidence of CAPA in the vaccination era. Our findings warrant investigation of antifungal prophylaxis in critically ill patients with COVID-19.

Fungal co-infections increase the incidence and mortality of viral respiratory tract infections. This study systematically reviews and conducts a meta-analysis to evaluate the prevalence of COVID-19 patients with fungal coinfections. The aim is to provide a concise overview of the impact of these infections on patient outcomes especially association with risk of mortality, informing future research and optimizing patient management strategies.

To identify relevant studies on COVID-19 patients, we conducted a systematic search of databases from the beginning of the year until July 2023, including fungal co-infections, mortality, and sequelae. Eligibility criteria were developed using the PICO framework, and data extraction was carried out separately by two authors using standard techniques. Statistical analysis was performed using the correlation model and differences between studies were evaluated using the I2 test. R and RStudio were used for statistical analysis and visualization.

We initially identified 6,764 studies, and after checking for equivalence and consistency, 41 studies were included in the final analysis. The overall COVID-19 odds ratio for people who died from fungal infections was 2.65, indicating that patients infected with both COVID-19 and fungal infections had a higher risk of death compared to patients with COVID-19 alone. Specifically, COVID-19-associated pulmonary aspergillosis (CAPA) has a higher odds ratio of 3.36, while COVID-19-associated candidiasis (CAC) has an odds ratio of 1.84, and both are much more associated with death. However, coinfection of the fungus with other fungal species did not show a significant difference in the risk of mortality.

This study identified CAPA and CAC as the most common infections acquired in healthcare settings. Fungal coinfections may be associated with an increased risk of death in COVID-19 patients.

Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker of infection, although the optimal cutoff for IPA is unclear. We aimed to evaluate the BAL fluid GM and fungal culture results, demographics, and outcomes among a large cohort of mechanically ventilated patients with suspected pneumonia.

A single-center cohort study of patients enrolled in the Successful Clinical Response in Pneumonia Therapy (SCRIPT) study from June 2018 to March 2023. Demographics, BAL results, and outcomes data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus on a BAL fluid culture, those who had elevated BAL fluid GM levels (defined as >0.5 or >0.8) but did not grow Aspergillus on BAL fluid culture, and those with neither.

Of over 1700 BAL samples from 688 patients, only 18 BAL samples grew Aspergillus. Patients who had a BAL sample grow Aspergillus (n=15) were older (median 71 vs 62 years, p=0.023), had more days intubated (29 vs 11, p=0.002), and more ICU days (34 vs 15, p=0.002) than patients whose BAL fluid culture was negative for Aspergillus (n=672). The BAL fluid galactomannan level was higher from samples that grew Aspergillus on culture than those that did not (median ODI 7.08 vs 0.11, p<0.001), though the elevation of BAL fluid GM varied across BAL samples for patients who had serial sampling. Patients who grew Aspergillus had a similar proportion of underlying immunocompromise compared with the patients who did not, and while no statistically significant difference in overall unfavorable outcome, had longer duration of ventilation and longer ICU stays.

In this large cohort of critically ill patients with a high number of BAL samples with GM levels, we found a relatively low rate of Aspergillus growth. Patients who eventually grew Aspergillus had inconsistently elevated BAL fluid GM, and many patients with elevated BAL fluid GM did not grow Aspergillus. These data suggest that the pre-test probability of invasive pulmonary aspergillosis should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Improved scoring systems are needed to enhance pre-test probability for diagnostic test stewardship purposes.

The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting of ECMO support, invasive fungal infections are a severe cause of morbidity and mortality. This vulnerable population is at risk of suboptimal antifungal exposure due to an increased volume of distribution (Vd), drug sequestration and decreased clearance. Here, we aimed to summarize ex-vivo and clinical studies on the potential impact of ECMO on the pharmacokinetics (PK) of antifungal agents and dosing requirements.

A systematic search of the literature within electronic databases PubMed and EMBASE was conducted from database inception to 30 April 2023. Inclusion criteria were as follows: critically ill patients receiving ECMO regardless of age and reporting at least one PK parameter.

Thirty-six studies met inclusion criteria, including seven ex-vivo experiments and 29 clinical studies evaluating three classes of antifungals: polyenes, triazoles and echinocandins. Based on the available ex-vivo PK data, we found a significant sequestration of highly lipophilic and protein-bound antifungals within the ECMO circuit such as voriconazole, posaconazole and micafungin but the PK of several antifungals remains to be addressed such as amphotericin B, isavuconazole and anidulafungin. Most clinical studies have shown increased Vd of some antifungals like fluconazole and micafungin, particularly in the pediatric population. Conflicting data exist about caspofungin exposure.

The available literature on the antifungal PK changes in ECMO setting is scarce. Whenever possible, therapeutic drug monitoring is highly advised to personalize antifungal therapy.

Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients.

We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes.

The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0-27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00-1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32-3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay.

Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality.

Mucormycosis and aspergillosis are angioinvasive infections mainly occurring in immunocompromised patients. However, mixed infection with mucormycosis and aspergillosis in post-COVID-19 patients is rare. In this report, we will report four cases and comprehensively review the published literature on COVID-19 associated mixed infection of aspergillosis and mucormycosis.

Besides four of our cases, we searched for published articles using PubMed/MEDLINE, Scopus, and Web of Science databases from the beginning of 2020 until October 2023.

During the COVID-19 pandemic, we analyzed 52 cases (4 from our research and 48 from other studies). The most common underlying disease (59.6%) was diabetes mellitus. However, 19.2% of COVID-19 patients had no underlying condition. Interestingly, rhino-orbital-cerebral mucormycosis featured prominently in India and Iran, while other countries primarily reported a higher prevalence of pulmonary cases.

In conclusion, this study highlights the presence of mixed aspergillosis and mucormycosis in COVID-19 patients who previously had common underlying diseases or even a healthy immune system. Therefore, managing COVID-19 patients should involve screening serum and respiratory samples using biomarkers to detect superinfections.

Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.

From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples.

Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77).

In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables.

People with immune deficiency are at risk of developing infections caused by several bacterial and fungal species. In this work, chitosan-coated miconazole was developed by a simple sol-gel method. Miconazole is considered an effective drug to treat vaginal infection-causing bacteria and fungi. The coating of chitosan with miconazole nitrate showed the highest drug loading efficiency (62.43%) and mean particle size (2 μm). FTIR spectroscopic analysis confirmed the entrapment of miconazole nitrate into chitosan polymer. The antifungal result demonstrated that MN@CS microgel possessed notable anti-Aspergillus fumigatus and Candida albicans activity in lower doses. Antibacterial activity results revealed excellent bacterial growth inhibition of MN@CS microgel towards human skin infectious pathogens Escherichia coli and Staphylococcus aureus. The biocompatibility studies of In vitro cell viability and Artemia salina lethality assay suggested that MN@CS microgel is more biosafe and suitable for human external applications. In the future, it will be an efficient anti-inflammatory agent for the treatment of vaginal infections.

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.

Coronavirus disease 2019 (COVID-19)-associated invasive pulmonary aspergillosis presents a diagnostic challenge due to its non-specific clinical/ imaging features, as well as the fact that the proposed clinically diagnostic algorithms do not necessarily apply to COVID-19 patients. In addition, Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. Disseminated Fusarium infection in an immunocompromised host is intractable, with a high likelihood of resulting mortality. To our knowledge, this is the first case of secondary pulmonary infection by Fusarium solani (F. solani) and Aspergillus niger (A. niger) during systemic steroid treatment for COVID-19.

A 62-year-old male was transported to our hospital by ambulance with a complaint of fever and dyspnea. We established a diagnosis of pneumococcal pneumonia, complicated with COVID-19 and septic shock, together with acute renal failure. He was admitted to the intensive care unit, to be treated with piperacillin/tazobactam, vancomycin, and 6.6 mg per day of dexamethasone sodium phosphate, along with noradrenaline as a vasopressor, ventilator management, and continuous hemodiafiltration. His condition improved, and we finished the vasopressor on the fifth hospital day. We administered dexamethasone for ten days, and finished the course of treatment. On the eleventh day, patient respiratory deterioration was observed, and a computed tomography scan showed an exacerbation of bilateral ground-glass-opacity-like consolidation, together with newly appeared cavitary lesions in the lung. we changed antibiotics to meropenem plus vancomycin. In addition, a fungal infection was considered as a possibility based on microscopic findings of sputum, and we began coadministration of voriconazole. However, the pneumonia worsened, and the patient died on the seventeenth day of illness. Later, F. solani and A. niger were identified from sputum collected on the twelfth day. It was believed that he developed a cell-mediated immune deficiency during COVID-19 treatment, which led to the complication of pneumonia caused by the above-mentioned fungi, contributing to his death.

Because early initiation of intense antifungal therapy offers the best chance for survival in pulmonary fusariosis, computed tomography scans and appropriate microbiologic investigations should be obtained for severely immunocompromised patients.

The SARS-CoV-2 pandemic has resulted in a public health emergency with unique complications such as the development of fungal co-infections. The diagnosis of fungal infections can be challenging due to confounding imaging studies and difficulty obtaining histopathology. In this retrospective study, 173 patients with COVID-19 receiving antifungal therapy due to concern for fungal co-infection were evaluated. Patient characteristics, clinical outcomes, and the utility of fungal biomarkers were then evaluated for continuation of antifungal therapy. Data were collected from the electronic health record (EPIC) and analyzed using SPSS (version. 28, IBM, Inc., Armonk, NY, USA) Data are presented as mean ± SD or percentages. A total of 56 COVID-19 patients were diagnosed with fungal co-infection and 117 COVID-19 + patients had no fungal infection. Significantly fewer female patients were in the fungal+ group compared to COVID-19 control patients (29% in fungal+ compared to 51% in controls p = 0.005). Fungal diagnostics were all significantly higher in fungal+ patients. These include 1,4-beta-D-glucan (BDG), fungal culture, and bronchoalveolar lavage galactomannan (BAL GM). Intensive care unit hospitalization, mechanical ventilation, and mortality in fungal+ patients with COVID-19 were significantly higher than in control patients. Finally, significantly more fungal+ patients received voriconazole, isavuconazonium, or amphotericin B therapies, whereas control patients received significantly more short-course fluconazole. COVID-19+ patients with fungal co-infection were significantly more likely to be in the ICU and mechanically ventilated, and they result in higher mortality compared to control COVID-19 patients. The use of fungal diagnostics markers were helpful for diagnosis.

Renal aspergillosis is a rare condition and this case the first case of Renal aspergillosis reported after COVID-19-associated pulmonary aspergillosis. Renal symptoms should arise clinical suspicion to renal involvement that happened as a result of hematogenous spreading of pulmonary aspergillosis.

Secondary fungal infections are among the most significant complications that can arise after COVID-19 and have the potential to lead to a high rate of morbidity and mortality. As COVID-19 primarily involves the airway, the majority of fungal infections reported have been related to the respiratory system. However, renal aspergillosis that we have reported is a rare condition that also can occur. A 67-year-old man was referred to our hospital and admitted as a COVID-19 patient. After the initial recovery, he experienced a recurrence of fever accompanied by a productive cough. The histopathological studies were conducted on the sputum and bronchoalveolar lavage samples, which revealed the presence of Aspergillus flavus. We treated the patient with voriconazole and the patient was discharged after a period of time. However, after approximately 6 months, he returned to the hospital with a fever and abdominal pain. We started a fever workup. Two new hypoechoic abscess-like masses were spotted in the right kidney in the ultrasonography (U/S) and the direct molecular studies of the biopsy sample obtained under U/S guidance identified Aspergillus flavus. Although renal aspergillosis is a rare condition, it should not be overlooked, especially in patients with severe COVID-19 and pulmonary aspergillosis, as these conditions can lead to renal aspergillosis, which may present with symptoms such as abdominal pain with fever. Therefore, it is necessary to perform radiological and histopathological studies when renal aspergillosis is suspected.

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Invasive fungal disease (IFD) is associated with the mortality of patients on extracorporeal membrane oxygenation (ECMO). Several risk factors for IFD have been identified in patients with or without ECMO. Here, we assessed the relevance of coronavirus disease (COVID-19) for the occurrence of IFD in patients on veno-venous (V-V) ECMO for respiratory failure. In a retrospective analysis of all ECMO cases between January 2013 and December 2022 (2020-2022 for COVID-19 patients), active COVID-19 and the type, timing and duration of IFD were investigated. Demographics, hospital, ICU length of stay (LoS), duration of ECMO, days on invasive mechanical ventilation, prognostic scores (Respiratory ECMO Survival Prediction (RESP) score, Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS)-10, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score (SAPS)-II) and length of survival were assessed. The association of COVID-19 with IFD was investigated using propensity score matching and uni- and multivariable logistic regression analyses. We identified 814 patients supported with ECMO, and 452 patients were included in further analyses. The incidence of IFD was 4.8% and 11.0% in patients without and with COVID-19, respectively. COVID-19 status represented an independent risk factor for IFD (OR 4.30; CI 1.72-10.85; p: 0.002; multivariable regression analysis). In patients with COVID-19, 84.6% of IFD was candidemia and 15.4% represented invasive aspergillosis (IA). All of these patients died. In patients on V-V ECMO, we report that COVID-19 is an independent risk factor for IFD, which is associated with a detrimental prognosis. Further studies are needed to investigate strategies of antifungal therapy or prophylaxis in these patients.

COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication affecting patients with severe SARS-CoV-2 infection, and is associated with increased mortality.

The objective of this study was to investigate potential risk factors, and to estimate the incidence and mortality in patients diagnosed with CAPA.

A single-center retrospective observational study was conducted on patients admitted to the intensive care unit (ICU) with severe COVID-19 from October 2020 to May 2022. Patients with deterioration of their clinical status were evaluated with serum galactomannan (GM) for probable CAPA. Baseline demographic patient characteristics, vaccination status, and time period during which each patient was infected with SARS-CoV-2 were obtained, and risk stratification according to underlying comorbidities was performed in an effort to assess various risk factors for CAPA. The incidence of CAPA in the entire cohort was measured, and mortality rates in the CAPA and non-CAPA groups were calculated and compared.

Of 488 patients admitted to the ICU, 95 (19.4%) had deterioration of their clinical status, which prompted testing with serum GM. Positive serum testing was observed in 39/95 patients, with an overall CAPA incidence in the entire study cohort reaching 7.9% (39/488). The mortality rate was 75% (42/56) in the non-CAPA group that was tested for serum GM, and 87.2% (34/39) in the CAPA group (P = 0.041). Multivariable Cox regression hazard models were tested for 28- and 90-day survival from ICU admission. An invasive pulmonary aspergillosis (IPA) risk-stratified cox regression model corrected for the SARS-CoV-2 variant of the patient identified the diagnosis of probable CAPA and elevated procalcitonin (PCT) levels measured at least 10 days after ICU admission, as significantly associated with death in the IPA-risk subgroup only, with hazard ratio (HR): 3.687 (95% confidence interval [CI], 1.030-13.199, P = 0.045) for the diagnosis of probable CAPA, and HR: 1.022 (95% CI, 1.003-1.042, P = 0.026) for every 1 ng/mL rise in PCT.

Patients in the IPA-risk subgroup that were diagnosed with CAPA had a lower 90-day survival when compared to patients in the same group without a CAPA diagnosis.

In 2020, we reported the first patient with concomitant COVID-19 and paracoccidioidomycosis (PCM). Since then, no other cases have been recorded in the literature. We aim to update information on the occurrence of COVID-19 in patients with PCM followed at a reference center for infectious diseases at Rio de Janeiro, Brazil.

We reviewed the medical records from patients diagnosed with PCM who presented with clinical symptoms, radiological findings, and/or laboratory diagnosis of COVID-19 at any time during their acute or follow-up care. The clinical profiles of these patients were described.

Between March 2020 and September 2022, we identified six individuals with COVID-19 among the 117 patients with PCM evaluated. The median age was 38 years and the male to female ratio 2:1. Most patients (n = 5) presented for evaluation due to acute PCM. The severity of COVID-19 ranged from mild to severe in acute PCM and only the single patient with chronic PCM died.

There is a range of disease severity in COVID-19 and PCM co-infection and concomitant disease may represent a severe association, especially in the chronic type of the mycosis with pulmonary involvement. As COVID-19 and chronic PCM share similar clinical aspects and PCM is neglected, it is probable that COVID-19 has been hampering simultaneous PCM diagnosis, which can explain the absence of new co-infection reports. With the continued persistence of COVID-19 globally, these findings further suggest that more attention by providers is necessary to identify co-infections with Paracoccidioides.

Critically ill COVID-19 patients are highly susceptible to opportunistic fungal infection due to many factors, including virus-induced immune dysregulation, host-related comorbidities, overuse and misuse of antibiotics or corticosteroids, immune modulator drugs, and the emergencies caused by the pandemic. This study aimed to assess the incidence, identify the potential risk factors, and examine the impact of fungal coinfection on the outcomes of COVID-19 patients admitted to the intensive care unit (ICU).

A prospective cohort study including 253 critically ill COVID-19 patients aged 18 years or older admitted to the isolation ICU of Zagazig University Hospitals over a 4-month period from May 2021 to August 2021 was conducted. The detection of a fungal infection was carried out.

Eighty-three (83) patients (32.8%) were diagnosed with a fungal coinfection. Candida was the most frequently isolated fungus in 61 (24.1%) of 253 critically ill COVID-19 patients, followed by molds, which included Aspergillus 11 (4.3%) and mucormycosis in five patients (1.97%), and six patients (2.4%) diagnosed with other rare fungi. Poor diabetic control, prolonged or high-dose steroids, and multiple comorbidities were all possible risk factors for fungal coinfection [OR (95% CI) = 10.21 (3.43-30.39), 14.1 (5.67-35.10), 14.57 (5.83-33.78), and 4.57 (1.83-14.88), respectively].

Fungal coinfection is a common complication of critically ill COVID-19 patients admitted to the ICU. Candidiasis, aspergillosis, and mucormycosis are the most common COVID-19-associated fungal infections and have a great impact on mortality rates.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

The incidence and outcome of pulmonary aspergillosis in coronavirus disease (COVID-19) patients on extracorporeal membrane oxygenation (ECMO) are unknown and have not been fully addressed. We investigated the incidence, risk factors and outcome of pulmonary aspergillosis in COVID-19 ECMO patients. In addition, the diagnostic utility of bronchoalveolar lavage fluid and CT scans in this setting were assessed.

We conducted a retrospective study on incidence and outcome of pulmonary aspergillosis in COVID-19 ECMO patients by reviewing clinical, radiological, and mycological evidence. These patients were admitted to a tertiary cardiothoracic centre during the early COVID-19 surge between March 2020 and January 2021. Results and measurements: The study included 88 predominantly male COVID-19 ECMO patients with a median age and a BMI of 48 years and 32 kg/m2, respectively. Pulmonary aspergillosis incidence was 10% and was associated with very high mortality. Patients with an Aspergillus infection were almost eight times more likely to die compared with those without infection in multivariate analysis (OR 7.81, 95% CI: 1.20-50.68). BALF GM correlated well with culture results, with a Kappa value of 0.8 (95% CI: 0.6, 1.0). However, serum galactomannan (GM) and serum (1-3)-β-D-glucan (BDG) lacked sensitivity. Thoracic computed tomography (CT) diagnostic utility was also inconclusive, showing nonspecific ground glass opacities in almost all patients.

In COVID-19 ECMO patients, pulmonary aspergillosis incidence was 10% and associated with very high mortality. Our results support the role of BALF in the diagnosis of pulmonary aspergillosis in COVID-19 ECMO patients. However, the diagnostic utility of BDG, serum GM, and CT scans is unclear.

A 55-year-old man was admitted for coronavirus disease 2019 (COVID-19)-related respiratory failure. He was treated with corticosteroids and tocilizumab in the intensive care unit. Aspergillus fumigatus (A. fumigatus) was isolated from his sputum on admission. However, no radiological findings suggesting pulmonary aspergillosis were seen on chest computed tomography (CT). Since the fungus had merely colonized in airways, antifungal drugs were not administered immediately. On day 19 of hospitalization, a high (1→3)-β-D-glucan (BDG) level was noted. A CT scan on day 22 revealed consolidations with a cavity in the right lung. A. fumigatus was isolated from his sputum again. Thus, we diagnosed the patient with COVID-19-associated pulmonary aspergillosis (CAPA) and started voriconazole. After the treatment, BDG levels and radiological findings were noted to improve. In this case, tocilizumab probably had a critical role in developing the disease. Although antifungal prophylaxis therapy for CAPA is not well established, this case shows that detecting Aspergillus in airway specimens before the disease onset possibly implies a high risk of developing CAPA and is an indicator of antifungal prophylaxis.

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.

The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA.

This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Incidence of CAPA and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor in a logistic regression model.

A total of 278 patients were included (n = 169 for ≤10 days' steroid duration; n = 109 for >10 days). CAPA developed in 20 of 278 (7.2%) patients. Patients treated with >10 days of corticosteroid therapy had significantly higher incidence of CAPA (11.9% vs 4.1%; P = .0156), and steroid duration >10 days was independently associated with CAPA (odds ratio, 3.17 [95% confidence interval, 1.02-9.83]). Secondary outcomes including inpatient mortality (77.1% vs 43.2%; P < .0001), mechanical ventilation-free days at 28 days (0 vs 1.5; P < .0001), and secondary infections (44.9% vs 28.4% P = .0220) were worse in the >10 days cohort.

Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.