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Purpose: We evaluated the interest of systematic screening of serum fungal markers in patients hospitalized in a medical ward., Methods: We retrospectively analyzed all patients hospitalized in our infectious disease department from October 1st to October 31st, 2020 for COVID-19 without prior ICU admission, and for whom systematic screening of serum fungal markers was performed., Results: Thirty patients were included. The majority of patients received corticosteroids (96.7%). The galactomannan antigen assay was positive for 1/30 patients at D0, and 0/24, 0/16, 0/13 and 0/2 at D4, D7, D10 and D14 respectively. 1,3-ß-D-glucan was positive for 0/30, 1/24, 1/12, 0/12, 0/2 at D0, D4, D7, D10 and D14 respectively. No Aspergillus fumigatus PCR was positive. No cases of aspergillosis were retained., Conclusion: Our study does not support the interest of systematic screening of fungal markers in immunocompetent patients with COVID-19 in a conventional unit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Invasive pulmonary aspergillosis (IPA) is an important complication of coronavirus disease 2019 (COVID-19), and while there are case reports and epidemiological studies, few studies have isolated Aspergillus strains from patients. Therefore, we analyzed the strains, sensitivities, and genetic homology of Aspergillus spp. Isolated from patients with COVID-19., Methods: We investigated the Aspergillus strains detected from patients with COVID-19 hospitalized in Osaka Metropolitan University Hospital from December 2020 to June 2021. A molecular epidemiological analysis of Aspergillus spp. was performed using drug susceptibility tests and TRESPERG typing, and data on patient characteristics were collected from electronic medical records., Results: Twelve strains of Aspergillus were detected in 11 of the 122 patients (9%) with COVID-19. A. fumigatus was the most common species detected, followed by one strain each of Aspergillus aureolus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus. A. aureolus was resistant to voriconazole, and no resistance was found in other strains. All A. fumigatus strains were genetically distinct strains. Six of the 11 patients that harbored Aspergillus received antifungal drug treatment and tested positive for β-D-glucan and/or Aspergillus galactomannan antigen. The results indicated that Aspergillus infections were acquired from outside the hospital and not from nosocomial infections., Conclusion: Strict surveillance of Aspergillus spp. is beneficial in patients at high-risk for IPA. When Aspergillus is detected, it is important to monitor the onset of IPA carefully and identify the strain, perform drug sensitivity tests, and facilitate early administration of therapeutic agents to patients with IPA., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Coronavirus disease 2019 (COVID‐19)‐associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID‐19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited. Objectives: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID‐19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID‐19. Methods: We investigated the incidence of CAPA in patients with severe and critical COVID‐19 using administrative claims data from acute care hospitals in Japan. We employed multivariable regression models to explore potential risk factors for CAPA and their contribution to mortality in patients with severe and critical COVID‐19. Results: The incidence of CAPA was 0.4%–2.7% in 33,136 patients with severe to critical COVID‐19. Age, male sex, chronic lung disease, steroids, immunosuppressants, intensive care unit admission, blood transfusion and dialysis were potential risk factors for CAPA in patients with severe to critical COVID‐19. CAPA was an independent factor associated with mortality. Conclusions: CAPA is a serious complication in patients with severe and critical COVID‐19 and may increase mortality. [ABSTRACT FROM AUTHOR]

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA–EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60–72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2–5), and the simplified acute physiology score (SAPS)-II score was 42 (31–56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10–21.75) after symptoms onset and 9 days (IQR 3–11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis—in the absence of specific invasive investigations, and with a consequent possible increase in mortality—and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians. [ABSTRACT FROM AUTHOR]

Background: COVID‐19‐associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real‐world insights about the disease. Methods: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non‐CAPA and deceased/survived CAPA patients using univariable and multivariable models. Results: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non‐CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1–2.8]). Diabetes (odds ratio [OR] 1.92 [1.15–3.21]); persistent fever (2.54 [1.17–5.53]); hemoptysis (7.91 [4.45–14.06]); and lung lesions of cavitation (8.78 [2.27–34.03]), consolidation (9.06 [2.03–40.39]), and nodules (8.26 [2.39–28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09–6.55]), a high computed tomography score index (OR 1.18 [1.08–1.29]; p <.001), and pulse glucocorticoid treatment (HR 4.0 [1.3–9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03–1.15] and mortality: 1.17 [1.08–1.28]) and lymphopenia (development: 0.68 [0.51–0.91] and mortality: 0.40 [0.20–0.83]) were associated with the development as well as mortality of CAPA. Conclusion: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality. [ABSTRACT FROM AUTHOR]

Background: Galactomannan Enzyme Immunoassay (GM‐EIA) is proved to be a cornerstone in the diagnosis of COVID‐19‐associated pulmonary aspergillosis (CAPA), its use is limited in middle and low‐income countries, where the application of simple and rapid test, including Galactomannan Lateral Flow Assay (GM‐LFA), is highly appreciated. Despite such merits, limited studies directly compared GM‐LFA with GM‐EIA. Herein we compared the diagnostic features of GM‐LFA, GM‐EIA and bronchoalveolar lavage (BAL) culture for CAPA diagnosis in Iran, a developing country. Materials/Methods: Diagnostic performances of GM‐LFA and GM‐EIA in BAL (GM indexes ≥1) and serum (GM indexes >0.5), i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and areas under the curve (AUC), were evaluated using BAL (n = 105) and serum (n = 101) samples from mechanically ventilated COVID‐19 patients in intensive care units. Patients were classified based on the presence of host factors, radiological findings and mycological evidences according to 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. Results: The Aspergillus GM‐LFA for serum and BAL samples showed a sensitivity of 56.3% and 60.6%, specificity of 94.2% and 88.9%, PPV of 81.8% and 71.4%, NPV of 82.3% and 83.1%, when compared with BAL culture, respectively. GM‐EIA showed sensitivities of 46.9% and 54.5%, specificities of 100% and 91.7%, PPVs of 100% and 75%, NPVs of 80.2% and 81.5% for serum and BAL samples, respectively. Conclusion: Our study found GM‐LFA as a reliable simple and rapid diagnostic tool, which could circumvent the shortcomings of culture and GM‐EIA and be pivotal in timely initiation of antifungal treatment. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) causes severe pneumonia and acute respiratory distress syndrome. According to the current consensus, immunosuppressants, such as dexamethasone and anti-interleukin-6 receptor monoclonal antibodies, are therapeutic medications in the early stages of infection. However, in critically ill patients, viral, fungal, and bacterial coinfection results in higher mortality. We conducted a single-center, retrospective analysis of 29 mechanically ventilated patients with artificial airways. Patients were adults with confirmed COVID-19 infection and severe pneumonia. Acute respiratory distress syndrome was diagnosed according to the Kigali modification of the Berlin definition. Six patients had invasive pulmonary aspergillosis coinfection based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid. We present two cases with brief histories and available clinical data. We also conducted a literature review to determine whether immunosuppressants, such as tocilizumab, increase infection risk or invasive aspergillosis in patients with COVID-19. There is no conclusive evidence to suggest that tocilizumab increases coinfection risk. However, further studies are needed to determine the optimal dose, between-dose interval, and timing of tocilizumab administration in patients with COVID-19. [ABSTRACT FROM AUTHOR]

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA–EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60–72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2–5), and the simplified acute physiology score (SAPS)-II score was 42 (31–56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10–21.75) after symptoms onset and 9 days (IQR 3–11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis—in the absence of specific invasive investigations, and with a consequent possible increase in mortality—and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians.

Invasive pulmonary aspergillosis (IPA) has always been a challenging diagnosis and risk factors an important guide to investigate specific population, especially in Intensive Care Unit. Traditionally recognized risk factors for IPA have been haematological diseases or condition associated with severe immunosuppression, lately completed by chronic conditions (such as obstructive pulmonary disease, liver cirrhosis, chronic kidney disease and diabetes), influenza infection and Intensive Care Unit (ICU) admission. Recently, a new association with SARS-CoV2 infection, named COVID-19-associated pulmonary aspergillosis (CAPA), has been reported worldwide, even if its basic epidemiological characteristics have not been completely established yet. In this narrative review, we aimed to explore the potential risk factors for the development of CAPA and to evaluate whether previous host factors or therapeutic approaches used in the treatment of COVID-19 critically ill patients (such as mechanical ventilation, intensive care management, corticosteroids, broad-spectrum antibiotics, immunomodulatory agents) may impact this new diagnostic category. Reviewing all English-language articles published from December 2019 to December 2020, we identified 21 papers describing risk factors, concerning host comorbidities, ICU management, and COVID-19 therapies. Although limited by the quality of the available literature, data seem to confirm the role of previous host risk factors, especially respiratory diseases. However, the attention is shifting from patients' related risk factors to factors characterizing the hospital and intensive care course, deeply influenced by specific features of COVID treatment itself. Prolonged invasive or non-invasive respiratory support, as well as the impact of corticosteroids and/or immunobiological therapies seem to play a pivotal role. ICU setting related factors, such as environmental factors, isolation conditions, ventilation systems, building renovation works, and temporal spread with respect to pandemic waves, need to be considered. Large, prospective studies based on new risk factors specific for CAPA are warranted to guide surveillance and decision of when and how to treat this particular population. [ABSTRACT FROM AUTHOR]