Table 4.
Diagnostic criteria and algorithms used for the diagnosis of CAPA.
| EORTC/MSG criteria, 2020 revision [59] |
|---|
| Proven Aspergillosis: 6/213 (2.8%) CAPA cases |
| Histopathologic, cytopathologic, or direct microscopic examination of a specimen obtained by needle aspiration or biopsy in which hyphae are seen accompanied by evidence of associated tissue damage. |
| Culture on sterile material: recovery of Aspergillus spp. by culture of a specimen obtained by lung biopsy. Amplification of fungal DNA by PCR combined with DNA sequencing when molds are seen in formalin-fixed paraffin-embedded tissue. |
| Probable Aspergillosis: 31/213 (14.6%) CAPA cases |
| At least 1 host factor, a clinical feature and mycologic evidence. |
| Host factors |
| 1. Recent history of neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days) temporally related to the onset of invasive fungal disease. |
| 2 .Hematologic malignancy. |
| 3. Receipt of an allogeneic stem cell transplant. |
| 4. Receipt of a solid organ transplant. |
| 5. Prolonged use of corticosteroids (excluding among patients with allergic broncho pulmonary aspergillosis) at a therapeutic dose of ≥0.3 mg/kg corticosteroids for ≥3 weeks in the past 60 days. |
| 6. Treatment with other recognized T-cell immuno suppressants, such as calcineurin inhibitors, tumor necrosis factor-a blockers, lymphocyte-specific monoclonal antibodies, immunosuppressive nucleoside analogues during the past 90 days. |
| 7. Treatment with recognized B-cell immuno suppressants, such as Bruton's tyrosine kinase inhibitors, e.g., ibrutinib. |
| 8. Inherited severe immunodeficiency (such as chronic granulomatous disease, STAT 3 deficiency, or severe combined immunodeficiency). |
| 9. Acute graft-vs.-host disease grade III or IV involving the gut, lungs, or liver that is refractory to first-line treatment with steroids. |
| Clinical features |
| The presence of 1 of the following 4 patterns on CT: |
| 1. Dense, well-circumscribed lesions(s) with or without a halo sign. |
| 2. Air crescent sign. |
| 3. Cavity. |
| 4. Wedge-shaped and segmental or lobar consolidation. |
| Mycological evidence |
| 1. Aspergillus recovered by culture from sputum, BAL, bronchial brush, or aspirate. |
| 2. Micro scopical detection of fungal elements in sputum, BAL, bronchial brush, or aspirate indicating a mold. |
| 3. GM antigen detected in plasma, serum, BAL. Any 1 of the following: |
| - Single serum or plasma: ≥1.0. |
| - BAL fluid: ≥1.0. |
| - Single serum or plasma: ≥0.7 and BAL fluid ≥0.8. |
| 4. Aspergillus PCR. Any 1 of the following: |
| - Plasma, serum, or whole blood 2 or more consecutive PCR tests positive, |
| - BAL fluid 2 or more duplicate PCR tests positive, |
| - At least 1 PCR test positive in plasma, serum, or whole blood and 1 PCR test positive in BAL fluid. |
| Possible Aspergillosis |
| A host factor and a clinical feature but not mycological evidence |
| AspICU algorithm, 2012[60] |
| Putative (all four criteria must be met): 133/213 (62.4%/) CAPA cases |
| 1. Aspergillus-positive lower respiratory tract specimen culture (entry criterion) |
| 2. Compatible signs and symptoms (one of the following) |
| - Fever refractory to at least 3 days of appropriate antibiotic therapy. |
| - Recrudescent fever after a period of defervescence of at least 48 h while still on antibiotics and without other apparent cause. |
| - Pleuritic chest pain or pleuritic rub. |
| - Dyspnea. |
| - Hemoptysis. |
| - Worsening respiratory insufficiency in spite of appropriate antibiotic therapy and ventilatory support. |
| 3. Abnormal medical imaging by Chest X-ray or CT scan of the lungs |
| 4. Either 4a or 4b |
| 4a. Host risk factors (one of the following conditions) |
| - Neutropenia (absolute neutrophil count < 500/mm3) preceding or at the time of ICU admission |
| - Underlying hematological or oncological malignancy treated with cytotoxic agents |
| - Glucocorticoid treatment (prednisone equivalent, >20 mg/day) |
| - Congenital or acquired immunodeficiency |
| 4b. Semiquantitative Aspergillus-positive culture of BAL fluid (+ or ++), without bacterial growth together with a positive cytological smear showing branching hyphae |
| Colonization |
| When ≥1 criterion necessary for a diagnosis of putative IPA is not met |
| Modified AspICU algorithm, 2018[7] |
| AspICU algorithm 1,2,3 |
| Mycological criteria |
| One or more of the following: |
| - Histopathology or direct microscopic evidence of dichotomous septate hyphae with positive culture for Aspergillus from tissue |
| - A positive Aspergillus culture from a BAL. |
| A GM optical index on BAL of ≥1 |
| A GM optical index on serum of ≥0.5. |
| IAPA criteria 2020[46] |
| Probable: 38/213 (17.8%) CAPA cases |
| 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 |
| B: Cavitating infiltrate (not attributed to another cause) and at least one of the following: |
| Positive sputum culture or |
| Positive TA culture |
AspICU: A clinical algorithm to diagnose Invasive Pulmonary Aspergillosis in intensive care unit patients; BAL: Bronchoalveolar lavage; CT: Computed tomography; CAPA: COVID-19-associated aspergillosis; EORTC/MSG: European Organization for Research and Treatment of Cancer/Mycoses Study Group; GM: Galactomannan; IAPA: Influenza-associated pulmonary aspergillosis; ICU: Intensive care unit; IPA: Invasive pulmonary aspergillosis; PCR: Polymerase chain reaction; TA: Tracheal aspirate.