During the COVID-19 pandemic, many patients in intensive care units (ICUs) were affected by invasive fungal infections, including aspergillosis, contributing to a high mortality rate. Diagnosing proven COVID-19-associated pulmonary aspergillosis (CAPA) requires clinical and radiological evaluations, along with laboratory testing of bronchoalveolar lavage samples or lung biopsies. However, these procedures and equipment are often inaccessible in developing countries or regions with limited resources, including Brazil. Consequently, alternative diagnostic methods, such as measuring Aspergillus galactomannan (GM) in tracheal aspirate (TA), have been explored for CAPA diagnosis. Nonetheless, research on the efficacy of TA-based diagnostic tests is limited. This study aimed to assess the performance of the IMMY® Sona Aspergillus lateral flow assay (LFA) for GM detection in TA samples from 60 ICU patients with suspected CAPA at two tertiary hospitals in Campo Grande, Brazil. The ELISA method (Platelia Aspergillus AG, Bio-Rad®) was used to detect Aspergillus GM in TA samples, serving as the microbiological criterion and reference test. Fifteen patients (12.4%) were identified as having possible CAPA. The overall accuracy of LFA was 94%, and the tests demonstrated an agreement of 93.1% (Cohen\'s kappa of 0.83). Based on our findings, the LFA for Aspergillus GM detection in TA samples exhibited excellent performance, proving to be a valuable diagnostic tool for potential CAPA. In a systematic review, two studies were included, and the meta-analysis revealed pooled estimates provided a sensitivity of 86% (95% CI, 80%-91%) and specificity of 93% (95% CI, 86%-97%). The diagnostic odds ratio (DOR) for identification of Aspergillus using LFA was 103.38 (95% CI, 38.03-281.03). Despite its lower sensitivity compared to our study, the LFA appears to be a promising diagnostic option for CAPA, particularly in suspected cases that have not received antifungal therapy. This enables timely antifungal treatment and could reduce mortality rates in regions where bronchoscopy is unavailable or limited.

OBJECTIVE: The number of postanesthesia care unit (PACU) registered nurses (RNs) with a specialty nursing certification at an orthopedic hospital in an academic health system was below the organizational benchmark. A clinical nurse-led process was developed to increase the percentage of PACU RNs with a specialty certification. This article will describe the strategies and interventions identified to support, reward, and recognize nurses who obtain or maintain their specialty certifications.
METHODS: A performance improvement project using the Plan-Do-Study-Act cycle.
METHODS: A gap analysis identified barriers preventing PACU nurses from obtaining specialty certifications in an orthopedic acute care American Nurses Credentialing Center Magnet-designated hospital. An anonymous web-based survey was distributed to 18 nurses who, although eligible, were not certified. The survey assessed common barriers to certification (eg, cost of the examination, comfort level with the testing process, level of access to review courses and study materials, expense to maintain credentials, personal interest in certification, and awareness of qualification information to take the exam). The project team included PACU nurse leaders, certified clinical nurses, nursing professional development specialists, and other interdisciplinary team members (eg, content experts from different departments).
RESULTS: Eighteen RNs completed the anonymous survey. The leading barrier was the expense of the certification exam (73%), while 66% of respondents reported discomfort with the test-taking process. Additionally, 61% of nurses reported that more access to review courses and study materials is needed, 44% responded that the expense of maintaining credentials is a barrier, 39% responded that the additional compensation pay for a specialty certification was considered to be insufficient, 39% agreed there is a lack of information on eligibility criteria, and 6% responded that they have no interest or desire to become certified. The survey results informed implementation strategies to increase certification rates, including initiating peer-to-peer exam groups and ongoing collaboration with nurse leaders on reward and recognition strategies. The removal of known barriers to obtaining specialty certification significantly increased certification rates in the PACU. Over the project period, the percentage of PACU-certified nurses increased to 60%, exceeding the project goal of 51%.
CONCLUSIONS: Peer-to-peer education and collaboration with nursing leadership and other interdisciplinary team members helped increase PACU\'s certification rates in this orthopedic specialty hospital. The informational and recognition strategies were impactful, resulting in additional nurses interested in becoming certified. Newly certified nurses are now motivating others to seek certification. Based on this well-established support system, the PACU certification rate is anticipated to continue to rise.

Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.

UNASSIGNED: During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, those with severe COVID-19 infection were at risk for a number of opportunistic infections including COVID-19-associated pulmonary aspergillosis (CAPA). We initiated a randomized clinical trial to evaluate whether isavuconazole, a triazole antifungal, could prevent CAPA and improve survival in patients admitted to the ICU with severe COVID-19 infection.
UNASSIGNED: We designed a phase III/IV randomized, double-blind, two-arm, placebo-controlled trial evaluating standard of care (SOC) plus isavuconazole versus SOC plus placebo and were to enroll participants admitted to the ICU with severe COVID-19 infection at three medical centers in California, United States. The projected sample size was 162 participants.
UNASSIGNED: Due to poor enrollment and the declining number of COVID-19 cases over time, the study was terminated after 7 participants were enrolled, all enrolled at one study site (UC San Diego Health). CAPA was suspected in two participants and they were started on open-label isavuconazole. One was withdrawn due to possible isavuconazole-related adverse side effects.
UNASSIGNED: Enrollment was slower-than-expected due to multiple factors, including competing COVID-19-related studies and hesitancy from potential study participants or their families to join the study. Our experience highlights some of the difficulties in planning and running a clinical trial focused on fungal superinfections involving severely ill patients during the height of the COVID-19 pandemic. Lessons learned from this study will help in the design of proposed studies examining antifungal prophylaxis against aspergillosis following other severe respiratory viral infections.

The objective of this study was to investigate the risk factors and diagnosis measure of COVID-19-associated pulmonary aspergillosis (CAPA). This study included 201 COVID-19 patients from December 1, 2022, to January 31, 2023; 7 (3.5%) were diagnosed with CAPA. The main risk factors were age, MV, ICU admission and COPD, and the presence of comorbidities such as ARDS and hypoproteinemia in COVID-19 patients, more susceptible to Aspergillus infection. In addition to specimen culture in the lower respiratory tract, the 1,3-β-D-glucan antigen test can serve as an important screening indicator for early CAPA diagnosis in non-granulocytopenia patients.

The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.
[Box: see text].

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients.
METHODS: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients.
RESULTS: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort.
CONCLUSIONS: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

OBJECTIVE: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021.
METHODS: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded.
RESULTS: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole.
CONCLUSIONS: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.

UNASSIGNED: Fungal co-infection is prevalent in critically ill patients with COVID-19. The conventional approach applied to fungal identification has relatively low sensitivity and is time-consuming. The metagenomic next-generation sequencing (mNGS) technology can simultaneously detect a variety of microorganisms, and is increasingly being used for the rapid detection and diagnosis of pathogens.
UNASSIGNED: In this single-center retrospective study, we described the clinical presentation and outcomes of COVID-19 and mNGS positive for fungi in pulmonary critically ill patients during the outbreak of Omicron infection from December 2022 to January 2023.
UNASSIGNED: Among 43 COVID-19 patients with acute respiratory distress syndrome (ARDS) on a single intensive care unit (ICU), 10 were reported to be fungal positive using the mNGS test. The number of pathogenic microorganisms detected by mNGS was significantly higher than that via traditional methods, especially in the detection of fungi and viruses. Aspergillus infection was dominant, and most of these patients also had concurrent bacterial or viral infections. Probable or possible COVID-19-associated pulmonary aspergillosis (CAPA) was diagnosed in all 10 patients, and the prognosis was poor.
UNASSIGNED: Patients with COVID-19 may be at increased risk of developing fungal infections as well as concurrent bacterial or viral infections, and mNGS can be a powerful tool in identifying these infections. Clinicians should be aware of the increased risk of fungal infections in COVID-19 patients, particularly those who have underlying immunocompromising conditions, and should monitor for early signs of infection.

Several criteria exist to diagnose pulmonary aspergillosis with varying degrees of certainty in specific populations, including oncohaematological patients (EORTC/MSG), ICU patients (mAspICU) and COVID-19 patients (ECMM). At the beginning of the pandemic, however, the diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA) could not be performed easily, and the decision to treat (DTT) was empirical. In this cross-sectional retrospective study including patients with SARS-CoV-2 infection and suspicion of CAPA, we studied the concordance between the DTT and the three diagnostic criteria using Cohen\'s coefficient, and then we identified the factors associated with the DTT and corrected them by treatment to study the influence of the diagnostic criteria on survival. We showed good concordance of the DTT and mAspICU and ECMM criteria, with \"compatible signs\", \"positive culture\" and \"positive galactomannan\" influencing the DTT. Treatment also showed a positive effect on survival once corrected for a putative, possible or probable diagnosis of CAPA using mAspICU and ECMM criteria. We conclude that EORTC/MSGERC are not considered applicable in clinical practice due to the lack of inclusion of signs and symptoms and do not lead to improved survival. mAspICU and ECMM criteria showed a good degree of agreement with the DTT and a positive correlation with patient recovery.