A prospective multi-center observational study to assess the incidence of influenza-associated pulmonary aspergillosis (IAPA) in ICU patients and to identify host- and pathogen related risk factors for IAPA in EORTC negative ICU patients with severe influenza.

Invasive pulmonary aspergillosis was shown to be a complication of severe influenza infections in immunocompromised patients as well as in immunocompetent patients and is associated with a high mortality. Antifungal prophylaxis might prevent influenza-associated pulmonary aspergillosis (IAPA) and thus might improve the outcome in patients with severe influenza. However, clinical related risk factors should be identified to assess whether a patient will benefit from antifungal prophylaxis. This prospective multi-center observational study will assess the incidence of influenza-associated pulmonary aspergillosis (IAPA) in ICU patients in 12 ICUs in The Netherlands, Belgium and France over 4 influenza seasons. The secondary objective of this study is to identify host- and pathogen related risk factors for IAPA in EORTC negative ICU patients with severe influenza. Patients aged 18 or older admitted to the intensive care unit (ICU) during the inclusion period due severe influenza without classic risk factors defined by the EORTC will be included.

Inclusion Criteria:

• Patients with a PCR-positive respiratory virus panel (RVP) result for influenza within 96 hours before or 48 hours after ICU admission.
• Patients who require ICU admission for more than 24 hours for severe influenza.
• Patients who have respiratory distress (respiratory rate >= 25x/minute and paO2/fiO2 < 300 with or without bilateral infiltrates) as the main reason for ICU admission.
• Patients who do not have an EORTC host factor.
• Patients who are at least 18 years of age.

Exclusion Criteria:

• Patients with age < 18 years as extensive sampling is required
• Expected survival on ICU admission ≤ 48h
• Patients that are being treated actively with antifungal agents for invasive aspergillosis.
• Patients or their legal representatives who did not sign the informed consent form

The target patient population is the EORTC-negative population of critically ill influenza patients at ICU. Patient identification will rely on daily review of ICU patients with respiratory virus panels ordered in the previous 24 hours.