Aspergillus Test Profiles and Mortality in Critically Ill COVID-19 Patients.

The literature regarding COVID-19-associated pulmonary aspergillosis (CAPA) has shown conflicting observations, including survival of CAPA patients not receiving antifungal therapy and discrepancy between CAPA diagnosis and autopsy findings. To gain insight into the pathophysiology of CAPA, we performed a case-control study in which we compared Aspergillus test profiles in CAPA patients and controls in relation to intensive care unit (ICU) mortality. This was a multinational case-control study in which Aspergillus test results, use of antifungal therapy, and mortality were collected from critically ill COVID-19 patients. Patients were classified using the 2020 European Confederation for Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus case definitions. We analyzed 219 critically ill COVID-19 cases, including 1 proven, 38 probable, 19 possible CAPA cases, 21 Aspergillus-colonized patients, 7 patients only positive for serum (1,3)-ß-d-glucan (BDG), and 133 cases with no evidence of CAPA. Mortality was 53.8% in CAPA patients compared to 24.1% in patients without CAPA (P = 0.001). Positive serum galactomannan (GM) and BDG were associated with increased mortality compared to serum biomarker-negative CAPA patients (87.5% versus 41.7%, P = 0.046; 90.0% versus 42.1%, P = 0.029, respectively). For each point increase in GM or 10-point BDG serum concentration, the odds of death increased (GM, odds ratio [OR] 10.208, 95% confidence interval [CI], 1.621 to 64.291, P = 0.013; BDG, OR, 1.247, 95% CI, 1.029 to 1.511, P = 0.024). CAPA is a complex disease, probably involving a continuum of respiratory colonization, tissue invasion, and angioinvasion. Serum biomarkers are useful for staging CAPA disease progression and, if positive, indicate angioinvasion and a high probability of mortality. There is need for a biomarker that distinguishes between respiratory tract colonization and tissue-invasive CAPA disease.

Molecular Diagnosis of Yeast Infections.

PURPOSE OF REVIEW: The use of molecular tests to aid the diagnosis of invasive yeast infection, in particular invasive candidosis, has been described for over two decades, yet widespread application is limited, and diagnosis remains heavily dependent on classical microbiology. This article will review developments from the past decade in attempt to build on existing knowledge. It will highlight clinical performance and limitations while reviewing developments on recognized procedures; it will also provide insight into novel approaches incorporated in response to clinical demand (e.g. C. auris and antifungal resistance) or technological advances (e.g. next-generation sequencing). RECENT FINDINGS: Limited methodological standardization and, until recently, unavailability of commercial options have hindered the integration of molecular diagnostics for yeasts. The development of certain, novel commercial methods has received considerable evaluation allowing a greater understanding of individual assay performance, but widespread multicentre evaluation of most commercial kits is lacking. The detection of emerging pathogens (e.g. C. auris) has been enhanced by the development of molecular tests. Molecular methods are providing a better understanding of the mycobiome, mechanisms of resistance and epidemiology/phylogeny. SUMMARY: Despite over two decades of use, the incorporation of molecular methods to enhance the diagnosis of yeast infections remains limited to certain specialist centres. While the development of commercial tests will provide stimulus for broader application, further validation and reduced costs are required. Over the same period of time, Aspergillus PCR has become more widely accepted driven by international efforts to standardize methodology; it is critical that yeast PCR follows suit. Next-generation sequencing will provide significant information on the mycobiome, antifungal resistance mechanism and even broad-range detection directly from the specimen, which may be critical for the molecular detection of yeasts other than Candida species, which is currently limited.

A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit.

BACKGROUND: Fungal coinfection is a recognized complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in coronavirus disease 2019 (COVID-19) patients with severe respiratory distress are being reported, but comprehensive data are lacking. The aim of this study was to determine the incidence, risk factors, and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. METHODS: An evaluation of a national, multicenter, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. RESULTS: One-hundred and thirty-five adults (median age: 57, M/F: 2.2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P = .0387). The mortality rate was reduced by the use of antifungal therapy (mortality: 38.5% in patients receiving therapy vs 90% in patients not receiving therapy (P = .008). The use of corticosteroids (P = .007) and history of chronic respiratory disease (P = .05) increased the likelihood of aspergillosis. CONCLUSIONS: Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.