Immunology · Year 2 · from Immunology
Case 7: COVID-19-Associated Pulmonary Aspergillosis (CAPA)
Clinical Image
Source: Wikipedia - Aspergillosis - CC BY-SA 4.0
Case Presentation
A 66-year-old male with COPD (FEV1 48% predicted) and severe COVID-19 pneumonia has been mechanically ventilated in the ICU for 14 days. He received dexamethasone 6 mg daily for 10 days and an 8 mg/kg dose of tocilizumab on day 3 of admission. Despite initial improvement in oxygenation, he develops recurrent fevers to 39.6C, progressive leukocytosis (WBC 18.4 x 10^9/L), and worsening hypoxia requiring increasing ventilator support (FiO2 escalated from 0.40 to 0.70 over 72 hours). Tracheal aspirate cultures grow mold, and bronchoscopy with bronchoalveolar lavage (BAL) is performed. BAL fluid reveals septate hyphae with acute-angle (45-degree) dichotomous branching on GMS stain, consistent with Aspergillus species. BAL galactomannan index is 4.8 (positive >1.0), and serum galactomannan is 1.6. BAL culture confirms Aspergillus fumigatus with MIC to voriconazole of 0.5 mcg/mL (susceptible). Repeat CT chest demonstrates a new 3.2-cm cavitary lesion in the right upper lobe with surrounding ground-glass halo sign, along with nodular infiltrates in the left lower lobe. He is started on IV voriconazole 6 mg/kg every 12 hours for 2 loading doses then 4 mg/kg every 12 hours with therapeutic drug monitoring (target trough 1-5.5 mcg/mL). Despite antifungal therapy, his course is complicated by progressive respiratory failure, and he expires on ICU day 28.
Key Learning Points
- CAPA occurs in 10-30% of mechanically ventilated COVID-19 patients and carries mortality rates exceeding 50%; risk factors include prolonged corticosteroid use, IL-6 receptor blockade, structural lung disease (COPD, prior TB), and diabetes mellitus
- SARS-CoV-2 impairs pulmonary antifungal defenses through multiple mechanisms: viral-induced epithelial damage exposes the basement membrane to Aspergillus conidia, corticosteroids and tocilizumab suppress alveolar macrophage fungicidal activity and neutrophil recruitment, and COVID-19-associated lymphopenia reduces Th1/Th17 responses critical for anti-Aspergillus immunity
- Diagnosis of CAPA requires a high index of suspicion; serum galactomannan has poor sensitivity (approximately 30%) in non-neutropenic patients, making BAL galactomannan (sensitivity approximately 75-80%) and BAL culture essential -- the threshold for positivity in BAL galactomannan in CAPA is an index of 1.0 or greater
- Voriconazole is first-line therapy for invasive pulmonary aspergillosis and requires therapeutic drug monitoring due to nonlinear pharmacokinetics, CYP2C19 polymorphism-dependent metabolism, and potential hepatotoxicity; isavuconazole is an alternative with fewer drug interactions and no need for cyclodextrin vehicle (relevant in renal impairment)