Invasive pulmonary aspergillosis is an emerging co-infection in patients with influenza who are admitted to the ICU. An international team of experts proposed consensus case definitions of influenza-associated pulmonary aspergillosis in order to facilitate clinical studies and the definition may also be useful to study COVID-19-associated pulmonary aspergillosis. |
Introduction
Participants and methods
Expert review
Global epidemiology of influenza and IAPA
Pathogenesis of IAPA
Clinical presentation and diagnosis of IAPA
Discussion on clinical presentation and diagnosis of IAPA
Use of corticosteroids
Rationale for antifungal prophylaxis for IAPA
Treatment options and challenges for IAPA in the ICU
Discussion on antifungal treatment options and challenges for IAPA in the ICU
Consensus case definition for IAPA
Entry criterion
Host factors
Criteria to define proven and probable cases of IAPA
Entry criteria: influenza-like illness + positive influenza PCR or antigen + temporally relationship | ||
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Aspergillus tracheobronchitis | IAPA in patients without documented Aspergillus tracheobronchitis | |
Proven | Biopsy or brush specimen of airway plaque, pseudomembrane or ulcer showing hyphal elements and Aspergillus growth on culture or positive Aspergillus PCR in tissue | Lung biopsy showing invasive fungal elements and Aspergillus growth on culture or positive Aspergillus PCR in tissue |
Probable | Airway plaque, pseudomembrane or ulcer and at least one of the following: Serum GM index > 0.5 or BAL GM index ≥ 1.0 or Positive BAL culture or Positive tracheal aspirate culture or Positive sputum culture or Hyphae consistent with Aspergillus | A: Pulmonary infiltrate and at least one of the following: Serum GM index > 0.5 or BAL GM index ≥ 1.0 or Positive BAL culture OR B: Cavitating infiltrate (not attributed to another cause) and at least one of the following: Positive sputum culture or Positive tracheal aspirate culture |
Conclusion
Can the IAPA definitions be applied to COVID-19-associated pulmonary aspergillosis?
Factor | IAPA | CAPA |
---|---|---|
Host/Risk | 57% EORTC/MSGERC host factor negative [9] | |
IAPA associated with corticosteroid use [7] | IPA developed in SARS-2003-infected patients receiving corticosteroids [61] | |
Lymphopenia and chemokine-producing monocyte-derived FCN1 + macrophages causing hyperinflammation [62] | ||
Virus | Cell entry through sialic acids-2,6Gal: epithelial layer in lung including larger airways [63] | Cell entry through ACE2: type 2 pneumocytes and ciliated cells [64] |
Immune modulation by suppression of the NADPH oxidase complex [65] | No evidence for immunomodulatory effect on known antifungal host defense mechanisms, although this has not been extensively studied yet | |
Fungal infection | ||
Median time between ICU admission and CAPA diagnosis 6 days [59] | ||
Aspergillus diagnostics | ||
Secondary infections | In 80 of 342 (23.4%) ICU patients, most frequent pathogens S. pneumoniae, Pseudomonas aeruginosa and S. aureus [66] | In four of 13 (31%) ICU patients, pathogens not specified [67] |
ICU mortality | 45% in IAPA compared with 20% in influenza without IAPA (p < 0.0001) [9] | 33% in CAPA cases compared with 17% in COVID-19 without CAPA (p = 0.4) [59] (although mortality rates due to COVID-19 without CAPA vary enormous between countries and we have no clear data yet on the true mortality in ICU of COVID-19) |