COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study.
William Hurt, Jonathan Youngs, Jonathan Ball, Jonathan Edgeworth, Philip Hopkins, David R Jenkins, Susannah Leaver, Andrea Mazzella, S��le F Molloy, Silke Schelenz, Matt P Wise, P Lewis White, Hakeem Yusuff, Duncan Wyncoll, Tihana Bicanic
Author Information
William Hurt: Institute of Infection and Immunity, St George's University of London, London, UK whurt@sgul.ac.uk. ORCID
Jonathan Youngs: Institute of Infection and Immunity, St George's University of London, London, UK.
Jonathan Ball: Adult Critical Care, St George's University Hospitals NHS Foundation Trust, London, UK.
Jonathan Edgeworth: Clinical Infection and Microbiology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Philip Hopkins: Adult Critical Care, King's College Hospital NHS Foundation Trust, London, UK.
David R Jenkins: Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK.
Susannah Leaver: Adult Critical Care, St George's University Hospitals NHS Foundation Trust, London, UK.
Andrea Mazzella: Institute of Infection and Immunity, St George's University of London, London, UK.
S��le F Molloy: Institute of Infection and Immunity, St George's University of London, London, UK.
Silke Schelenz: Medical Microbiology, King's College Hospital NHS Foundation Trust, London, UK.
Matt P Wise: Adult Critical Care, University of Wales Hospital, Cardiff, UK.
P Lewis White: Microbiology, Public Health Wales, Cardiff, UK.
Hakeem Yusuff: Adult Critical Care, University Hospitals of Leicester NHS Trust, Leicester, UK.
Duncan Wyncoll: Adult Critical Care, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Tihana Bicanic: Institute of Infection and Immunity, St George's University of London, London, UK.
BACKGROUND: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort. METHODS: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples. RESULTS: Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16)���days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95%���CI 1.01 to 1.43 per 100���mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95%���CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95%���CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95%���CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95%���CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77). INTERPRETATION: In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables.
