key: cord-030061-55ntc4wj
authors: Helleberg, Marie; Steensen, Morten; Arendrup, Maiken Cavling
title: Invasive aspergillosis in patients with severe COVID-19 pneumonia
date: 2020-08-05
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.07.047
sha: 
doc_id: 30061
cord_uid: 55ntc4wj

nan

intensive care units (ICUs) due to respiratory failure. In recent years, it has been recognized that rates of 10 invasive aspergillosis are high (19%) among patients admitted to the ICU with severe influenza, including 11 those without other risk factors for invasive fungal infections (14%). 1 Influenza-associated aspergillosis is 12 diagnosed median 3 days after admission to the ICU and is associated with increased mortality (51% versus 13 28%, P=0.0001). 1 Other severe viral pneumonias may also increase the risk of invasive aspergillosis 14

significantly. 2-4 Recently few case reports of COVID-19-associated A. fumigatus infection have been 15

published, but the incidence of invasive aspergillosis in COVID-19 patients with critical illness is unknown. 5-6 16 Rigshospitalet, is a tertiary referral university hospital, and one of two centers for extracorporeal 17 membrane oxygenation (ECMO) in Denmark. We have treated eight COVID-19 patients with ECMO in the 18 period 15-03-2020 to 11-04-2020. Two of the eight patients were diagnosed with plausible pulmonary 19 aspergillosis due to worsening of respiratory insufficiency, pulmonary infiltrates despite antibacterial 20 therapy, and positive Aspergillus cultures and galactomannan antigen (GM) tests on samples of serum or 21 lower respiratory tract secretion. Biopsy or bronchoalveolar lavage (BAL) was not performed to confirm the 22 diagnosis of pulmonary aspergillosis to reduce risk of aggravation of respiratory failure and risk of 23 transmission of SARS-CoV-2. Thus, the diagnosis of pulmonary aspergillosis was plausible but not proven. 24

However, a therapeutic BAL was performed later in the disease course for one of the patients and GM 25 testing of the BAL fluid was positive. Clinical and mycological characteristics, treatment and outcomes of 26 the two patients are summarized in Table 1 . Both patients were middle-aged females. One had a history of 27 asthma and was treated with systemic corticosteroids (methylprednisolone 80 mg IV for two days then oral 28 prednisolone 37.5 mg for four days) upon admission, the other patient had no classical risk factors for 29 invasive aspergillosis. The ICU algorithm for diagnosis of putative invasive aspergillosis require 1) An 30

Aspergillus-positive lower respiratory tract specimen culture, 2) compatible symptoms, 3) abnormal chest 31 X-ray/CT scan and 4) either a host factor or a positive BAL culture and microscopy. 7 Gilead, Novartis, MSD, and SEGES. She is the current chairman of the EUCAST-AFST. 59 60

Author contributions 61

All authors contributed to conceptualization, formal analysis, investigation and resources. MH wrote the 62 original draft of the manuscript. All authors edited and reviewed the manuscript and approved the final 63 version. 64 

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COVID-19 Associated Pulmonary Aspergillosis

Fatal Invasive Aspergillosis and Coronavirus Disease in an 86 Immunocompetent Patient. Emerg Infect Dis

A clinical algorithm to diagnose invasive pulmonary 88 aspergillosis in critically ill patients

Revision and Update of the Consensus Definitions of 90

Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and 91 the Mycoses Study Group Education and Research Consortium