Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study

Abstract

Background

The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.

Methods

The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.

Results

The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% − 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).

Conclusions

The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.

Trial registration

ClinicalTrials.gov NCT04172610, registered November 21, 2019

Keywords:

• Influenza
• influenza-associated aspergillosis
• intensive care medicine
• invasive aspergillosis

Author contributions

All authors made substantial contributions to the present study. Anders Krifors, Ola Blennow, Johan Petersson, and Markus Castegren developed the original concept and research design. The preparation of materials, as well as data collection and analysis, were conducted collaboratively by all authors. The initial manuscript draft was written by Anders Krifors, with each author providing critical comments and suggestions for revisions. All authors reviewed and approved the final version of the manuscript to be published.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

The study was financially supported by the Regional research council Uppsala-Örebro and the Centre for Clinical Research Västmanland.