**Background:** Invasive pulmonary aspergillosis (IPA) is a serious complication in critically ill patients with severe viral pneumonia. Influenza-associated invasive aspergillosis (IAPA) has been reported in up to 19% of ICU patients with influenza and acute respiratory distress syndrome (ARDS), with mortality of 51% vs. 28% in influenza patients without IAPA. COVID-19-associated pulmonary aspergillosis (CAPA) incidence varies across registries (UK 14.1%, Italy 27.7%, Germany 26.3%, Netherlands 19.4%, France 19.6%), similar to IAPA rates. Both entities share risk factors including immune dysregulation, lymphopenia, diabetes mellitus, pre-existing lung disease, and immunosuppressive therapies. However, Aspergillus tracheobronchitis and serum galactomannan (GM) positivity are less common in CAPA than IAPA. An expert group was convened to establish practical recommendations for diagnosis and treatment of IAPA based on available evidence and experience with CAPA.
**Methods:** The CAPA/IAPA expert group defined 14 areas for recommendations. The PICO (patient, intervention, comparator, outcome) strategy was used to search PubMed with MeSH terms and free text for both CAPA and IAPA. Each expert developed recommendations for 2–3 areas, which were presented to the group in multiple meetings to reach consensus. The final recommendations were grouped into 12 sections covering: when to suspect fungal infection, diagnostic methods, treatment recommendations, management of resistance, drug interactions and antifungal level monitoring, treatment effectiveness monitoring, management of treatment failure, implications of corticosteroid use, indications for combination antifungal therapy, when to withdraw treatment, management of positive Aspergillus cultures, and antifungal prophylaxis.
**Key Results:** The recommendations include: (1) Suspect CAPA/IAPA in ICU patients with viral pneumonia and clinical deterioration not explained by other factors, particularly those with EORTC/MSGERC host risk criteria, prolonged/high-dose steroid use, prolonged mechanical ventilation, or structural lung injury. Co-infection should be considered at ICU admission, and early superinfection within 5–7 days. (2) For diagnosis, prioritize lower respiratory tract samples via bronchoscopy with BAL for culture, GM determination, calcofluor/KOH staining, and Aspergillus PCR. Lateral flow device tests are a valid alternative. Serum GM screening is not routinely recommended due to low sensitivity (only 20% positivity in CAPA series vs. 65% in IAPA). Chest CT is recommended for patients with new infiltrates, cavitated nodules, or halo sign. (3) For treatment, isavuconazole or liposomal amphotericin B are recommended as first-line drugs. Voriconazole is not considered first-line due to its narrow therapeutic window and interactions with dexamethasone and remdesivir. In IAPA, voriconazole interactions with cloxacillin are a concern. (4) For azole resistance, liposomal amphotericin B is recommended. The prevalence of azole-resistant Aspergillus isolates is 3.2% across 19 European countries (range 0–26%), with rates of 2–12% in clinical samples globally. In centers with >10% azole resistance, initial treatment with liposomal amphotericin B is recommended. (5) Therapeutic drug monitoring is recommended for voriconazole at least weekly (twice in the first week), especially in patients receiving corticosteroids, extracorporeal membrane oxygenation, or renal replacement therapy. Target voriconazole concentrations are 2–6 mg/L. (6) Corticosteroid therapy in influenza pneumonia is associated with increased mortality and higher superinfection rates and should not be used. In COVID-19, dexamethasone (6 mg) reduced mortality (RR 0.65; 95% CI 0.48–0.88 in mechanically ventilated patients), but no direct evidence exists on its impact in CAPA patients. (7) Combination therapy (voriconazole + anidulafungin) showed no significant difference in 6-week mortality (19.3% vs. 27.5%, p=0.09) in a multicenter trial of 459 IPA patients, though a post hoc analysis suggested benefit in serum GM-positive patients (15.7% vs. 27.3%, p=0.037). (8) Antifungal treatment duration should be 4–6 weeks in patients with adequate clinical response. (9) Antifungal prophylaxis is not recommended in patients with severe influenza/COVID-19 pneumonia undergoing mechanical ventilation.
**Clinical Implications:** The management of CAPA/IAPA remains challenging with limited evidence. The expert group emphasizes early diagnosis through bronchoscopy and BAL, early initiation of antifungal treatment when suspicion is high, and safe de-escalation once diagnosis is confirmed or excluded. The choice of antifungal agent should account for drug interactions common in critically ill patients, particularly with voriconazole. Therapeutic drug monitoring is essential when using voriconazole. Corticosteroid use should be avoided in influenza pneumonia but may be continued in COVID-19 patients who develop CAPA, as current data do not support discontinuation. The authors highlight the need for further studies on antifungal prophylaxis, optimal treatment duration, and the role of nebulized antifungals.