key: cord-0851256-59dprd33 authors: Segrelles‐Calvo, Gonzalo; Araújo, Glauber R. S.; Llopis‐Pastor, Estefanía; Carrillo, Javier; Hernández‐Hernández, Marta; Rey, Laura; Rodríguez Melean, Nestor; Escribano, Inés; Antón, Esther; Zamarro, Celia; García‐Salmones, Mercedes; Frases, Susana title: Prevalence of opportunistic invasive aspergillosis in COVID‐19 patients with severe pneumonia date: 2020-12-03 journal: Mycoses DOI: 10.1111/myc.13219 sha: 3bb31354257bda59d99404fe080c3a6688cf8339 doc_id: 851256 cord_uid: 59dprd33 BACKGROUND: As the global coronavirus pandemic (COVID‐19) spreads across the world, new clinical challenges emerge in the hospital landscape. Among these challenges, the increased risk of coinfections is a major threat to the patients. Although still in a low number, due to the short time of the pandemic, studies that identified a significant number of hospitalised patients with COVID‐19 who developed secondary fungal infections that led to serious complications and even death have been published. OBJECTIVES: In this scenario, we aim to determine the prevalence of invasive fungal infections (IFIs) and describe possible associated risk factors in patients admitted due to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. PATIENTS/METHODS: We designed an open prospective observational study at the Rey Juan Carlos University Hospital (Mostoles, Spain), during the period from February 1 to April 30, 2020. RESULTS: In this article, we reported seven patients with COVID‐19‐associated pulmonary aspergillosis (CAPA) who had a poor prognosis. Severely ill patients represent a high‐risk group; therefore, we must actively investigate the possibility of aspergillosis in all of these patients. Larger cohort studies are needed to unravel the role of COVID‐19 immunosuppressive therapy as a risk factor for aspergillosis. CONCLUSIONS: As the pandemic continues to spread across the world, further reports are needed to assess the frequency of emergent and highly resistant reemergent fungal infections during severe COVID‐19. These coinfections are leading a significant number of patients with COVID‐19 to death due to complications following the primary viral disease. Invasive fungal infections (IFIs) have an incidence of approximately 4.7 per 1000 patients and have been associated with high morbidity and mortality in critically ill and immunocompromised patients. The most important fungi isolated are Candida spp., Aspergillus spp., Cryptococcus spp. and Pneumocystis spp. 1 Although studies indicate an increase in IFI, the incidence is underestimated in clinical settings. 2 Invasive aspergillosis has been reported in critically ill patients with influenza. In the study by Schauwvlieghe et al, authors identified influenza as an independent risk factor for invasive pulmonary aspergillosis (IPA), associated with high mortality. 3 In previous coro- [5] [6] [7] [8] We hypothesised that the use of immunosuppressors could increase the risk of the patients to develop probable IPA. 9 In this scenario, we aim to determine the prevalence of IFIs and describe possible associated risk factors in patients admitted due to severe SARS-CoV-2 infection. We designed an open prospective observational study, which was conducted at the Rey Juan Carlos University Hospital (HURJ), during the period from February 1 to April 30, 2020 ( Figure 1) We included 215 adult patients respectively admitted to the RICU or to the intensive care unit (ICU), with a confirmed diagnosis of severe pneumonia caused by SARS-CoV-2 ( Figure 1 According to our protocol, from all patients admitted to the RICU or ICU, samples of respiratory secretions and nasal, oropharyngeal, rectal, urine and skin exudates were collected every two weeks. Samples of sputum, from patients with sputum production, were collected and processed for microbiology analysis. To obtain additional samples of respiratory secretions by a direct aspiration (bronchoaspirates, BAS) or by completing a bronchoalveolar lavage (BAL), a bronchoscopy was performed. For the BAL, we instilled three 50 ml aliquots of sterile physiological solution (150 ml in total) in the area with radiological involvement. Patients with a sustained fever above 38ºC, despite the use of For the diagnosis of fungal infections, the detection of the Aspergillus galactomannan antigen was carried out in the BAL sample by using the Platelia™ Aspergillus EIA assay (Bio-Rad, Marnes La Coquette, France). We considered that the result was positive when the Aspergillus-galactomannan antigen value was ≥0.5. We obtained the data from the electronic medical record system of our centre, which allows the access to medical and nursing comments, in addition to laboratory and radiology exams. We collected the data related to the socio-demographic situation of the patients as well as their baseline health situation. During the inpatient stay, the data regarding the clinical course of the disease, the treatment for COVID-19 and the unfavourable evolution of the disease, including the occurrence of a major complication, admission to the ICU, and death were analysed. A severe pneumonia was identified when there was failure of one or more organs, when the oxygen saturation measured by pulse oximetry was <90% in ambient air, or when the respiratory rate was The CURB-651 and MuLBSTA2 were used as severity indices for pneumonia, the latter being used as an indicator for viral pneumonia. According to the MuLBSTA score, we classified the patients as having a low risk (0-11 points, mortality 5.07%) or a high risk of mortality (≥12 points, mortality 33.92%) (Table S1 ). We considered a cutoff point of 12 from the MuLBSTA score to differentiate between the low-risk mortality group (0-11 points) and the high-risk mortality group (>12 points). 12, 13 The radiological involvement was classified according to the radiographic assessment of lung oedema (RALE). 14 To calculate the RALE score, the chest was divided into 4 quadrants. Each quadrant was scored, from zero to four, according to the extension of the alveolar opacities: zero, no involvement; one, <25% of involvement; two: 25%-50%; three: 50%-75% and four: >75%). The total result was obtained from the sum of the scores of each one of the quadrants. We analysed each lung separately, and we scored from zero to four points depending on the damage visualised in the radiological exam (maximum of eight points, adding up the punctuation of both lungs). A score below two was interpreted as mild involvement, between three and six points as moderate, and above 6 as severe involvement (Table S2 ). In summary, patients with COVID-19 and an invasive aspergillosis coinfection have a poor prognostic. Critically ill patients represented a high-risk group, and we should actively investigate the possibility of aspergillosis in all of these patients. Larger cohort studies are needed in order to understand the role of immunosuppressive therapy with COVID-19 as a risk factor for IPA. We acknowledge Dr Barbara Hissa for critical reading and scientific editing of the manuscript. This work was supported by the Brazilian agen- 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. 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