COVID-19-associated aspergillosis in a Brazilian referral centre: Diagnosis, risk factors and outcomes.

BACKGROUND: COVID-19 patients on mechanical ventilation are at risk to develop invasive aspergillosis. To provide additional data regarding this intriguing entity, we conducted a retrospective study describing risk factors, radiology and prognosis of this emerging entity in a Brazilian referral centre. METHODS: This retrospective study included intubated (≥18 years) patients with COVID-19 admitted from April 2020 until July 2021 that had bronchoscopy to investigate pulmonary co-infections. COVID-19-associated aspergillosis (CAPA) was defined according to the 2020 European Confederation of Medical Mycology/International Society of Human and Animal Mycosis consensus criteria. The performance of tracheal aspirate (TA) cultures to diagnose CAPA were described, as well as the radiological findings, risk factors and outcomes. RESULTS: Fourteen patients (14/87, 16%) had probable CAPA (0.9 cases per 100 ICU admissions). The sensitivity, specificity, positive predictive value and negative predictive value of TA for the diagnosis of CAPA were 85.7%, 73.1%, 46.2% and 95% respectively. Most of the radiological findings of CAPA were classified as typical of invasive pulmonary aspergillosis (64.3%). The overall mortality rate of probable CAPA was 71.4%. Age was the only independent risk factor for CAPA [p = .03; odds ratio (OR) 1.072]. CAPA patients under renal replacement therapy (RRT) may have a higher risk for a fatal outcome (p = .053, hazard ratio 8.047). CONCLUSIONS: CAPA was a prevalent co-infection in our cohort of patients under mechanical ventilation. Older patients had a higher risk to develop CAPA, and a poor prognosis may be associated with RRT.

Invasive pulmonary aspergillosis associated with viral pneumonitis.

The occurrence of invasive pulmonary aspergillosis (IPA) in critically ill patients with viral pneumonitis has increasingly been reported in recent years. Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are the two most common forms of this fungal infection. These diseases cause high mortality in patients, most of whom were previously immunocompetent. The pathogenesis of IAPA and CAPA is still not fully understood, but involves viral, fungal and host factors. In this article, we discuss several aspects regarding IAPA and CAPA, including their possible pathogenesis, the use of immunotherapy, and future challenges.

Incidence, diagnosis and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA): a systematic review.

COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. The purpose of this review was to discuss the incidence, characteristics, diagnostic criteria, biomarkers, and outcomes of hospitalized patients diagnosed with CAPA. A literature search was performed through Pubmed and Web of Science databases for articles published up to 20th March 2021. In 1421 COVID-19 patients, the overall CAPA incidence was 13.5% (range 2.5-35.0%). The majority required invasive mechanical ventilation (IMV). The time to CAPA diagnosis from illness onset varied between 8.0 and 16.0 days. However, the time to CAPA diagnosis from intensive care unit (ICU) admission and IMV initiation ranged between 4.0-15.0 days and 3.0-8.0 days. The most common diagnostic criteria were the modified AspICU-Dutch/Belgian Mycosis Study Group and IAPA-Verweij et al. A total of 77.6% of patients had positive lower respiratory tract cultures, other fungal biomarkers of bronchoalveolar lavage and serum galactomannan were positive in 45.3% and 18.2% of patients. The CAPA mortality rate was high at 48.4%, despite the widespread use of antifungals. Lengthy hospital and ICU stays ranging between 16.0-37.5 days and 10.5-37.0 days were observed. CAPA patients had prolonged IMV duration of 13.0-20.0 days. The true incidence of CAPA likely remains unknown as the diagnosis is limited by the lack of standardized diagnostic criteria that rely solely on microbiological data with direct or indirect detection of Aspergillus in respiratory specimens, particularly in clinical conditions with a low pretest probability. A well-designed, multi-centre study to determine the optimal diagnostic approach for CAPA is required.

[Invasive fungal infections in ICU patients - What's New?] / Invasive Pilzinfektionen bei Intensivpatienten ­ Was gibt es Neues?

Invasive fungal infections are gaining increasing importance in intensive care medicine. The aim of this article is to present an update on recent developments in the field of invasive fungal infection in critically ill patients. Particular emphasis is placed on the recently described invasive mold infections in patients with acute respiratory distress syndrome due to influenza or COVID-19. Detecting high-risk patients and the optimal diagnostic and therapeutic strategies play a decisive role to improve outcome.

COVID-19-associated invasive pulmonary aspergillosis in a tertiary care center in Mexico City.

Invasive pulmonary aspergillosis (IPA) is a severe infection caused by aspergillus sp. that usually develops in patients with severe immunosuppression. IPA has been recently described in critically ill COVID-19 patients (termed as COVID-associated pulmonary aspergillosis, or CAPA) that are otherwise immunocompetent. In order to describe the characteristics of patients with CAPA, we conducted a retrospective cohort study in a tertiary care center in Mexico City. We included all patients with confirmed COVID-19 admitted to the intensive care unit that had serum or bronchoalveolar lavage galactomannan measurements. We used the criteria proposed by Koehler et al. to establish the diagnosis of CAPA. Main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital mortality. Out of a total of 83 hospitalized patients with COVID-19 in the ICU, 16 (19.3%) met the criteria for CAPA. All patients diagnosed with CAPA required IMV whereas only 84% of the patients in the non-IPA group needed this intervention (P = 0.09). In the IPA group, 31% (n = 5) of the patients died, compared to 13% (n = 9) in the non-CAPA group (P = 0.08). We conclude that CAPA is a frequent co-infection in critically ill COVID-19 patients and is associated with a high mortality rate. The timely diagnosis and treatment of IPA in these patients is likely to improve their outcome. LAY SUMMARY: We studied the characteristics of patients with COVID-19-associated invasive pulmonary aspergillosis (CAPA). Patients with CAPA tended to need invasive mechanical ventilation more frequently and to have a higher mortality rate. Adequate resources for its management can improve their outcome.

SARS-CoV-2 and Aspergillus section Fumigati coinfection in an immunocompetent patient treated with corticosteroids.

BACKGROUND: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. CASE REPORT: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. CONCLUSIONS: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.

Putative invasive pulmonary aspergillosis in critically ill patients with COVID-19: An observational study from New York City.

BACKGROUND: Critically ill patients with coronavirus disease-2019 (COVID-19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors. PATIENTS/METHODS: We aimed to describe the clinical features of COVID-19-associated pulmonary aspergillosis at a single centre in New York City. We performed a retrospective chart review of all patients with COVID-19 with Aspergillus isolated from respiratory cultures. RESULTS: A total of seven patients with COVID-19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU. Four patients were classified as putative IPA. The median age was 79 years, and all patients were male. The patients had been mechanically ventilated for a mean of 6.8 days (range: 1-14 days) before Aspergillus isolation. Serum galactomannan level was positive for only one patient. The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit. All four patients died. CONCLUSIONS: Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID-19.

Fungal Co-infections Associated with Global COVID-19 Pandemic: A Clinical and Diagnostic Perspective from China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been sweeping across the globe. Based on a retrospective analysis of SARS and influenza data from China and worldwide, we surmise that the fungal co-infections associated with global COVID-19 might be missed or misdiagnosed. Although there are few publications, COVID-19 patients, especially severely ill or immunocompromised, have a higher probability of suffering from invasive mycoses. Aspergillus and Candida infections in COVID-19 patients will require early detection by a comprehensive diagnostic intervention (histopathology, direct microscopic examination, culture, (1,3)-ß-D-glucan, galactomannan, and PCR-based assays) to ensure effective treatments. We suggest it is prudent to assess the risk factors, the types of invasive mycosis, the strengths and limitations of diagnostic methods, clinical settings, and the need for standard or individualized treatment in COVID-19 patients. We provide a clinical flow diagram to assist the clinicians and laboratory experts in the management of aspergillosis, candidiasis, mucormycosis, or cryptococcosis as co-morbidities in COVID-19 patients.