Aspergillosis Complicating Severe Coronavirus Disease

Abstract

Aspergillosis complicating severe influenza infection has been increasingly detected worldwide. Recently, coronavirus disease-associated pulmonary aspergillosis (CAPA) has been detected through rapid reports, primarily from centers in Europe. We provide a case series of CAPA, adding 20 cases to the literature, with review of pathophysiology, diagnosis, and outcomes. The syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis, which is recognized most frequently in persons with neutropenia and in other immunocompromised persons. Combined with severe viral infection, aspergillosis comprises a constellation of airway-invasive and angio-invasive disease and results in risks associated with poor airway fungus clearance and killing, including virus- or inflammation-associated epithelial damage, systemic immunosuppression, and underlying lung disease. Radiologic abnormalities can vary, reflecting different pathologies. Prospective studies reporting poor outcomes in CAPA patients underscore the urgent need for strategies to improve diagnosis, prevention, and therapy.

Keywords: Aspergillus; COVID-19; SARS-CoV-2; aspergillosis; complications; coronavirus disease; fungal infections; fungi; respiratory infections; severe acute respiratory syndrome coronavirus 2; severe viral pneumonia; zoonoses.

Figure 1

Representative computed tomography (CT) scans for 9 patients with aspergillosis complicating severe viral pneumonia in patients with coronavirus disease. Scans were obtained at or around diagnosis of coronavirus disease–associated pulmonary aspergillosis in this series of patients, described in the Table (https://wwwnc.cdc.gov/EID/article/27/1/20-2896-T1.htm). Corresponding case-patients are indicated with lettered superscripts in the radiology column of Table 1. Examples of nodules and cavitating nodules are indicated by red arrows, and prominent airway thickening and bronchiectasis in ground glass opacities are indicated by red stars.

Figure 2

Timeline of cases, series, and cohort studies reported to describe emergence of coronavirus disease–associated pulmonary aspergillosis. Reports from China are indicated according to relative times that patients were given care; case series describing CAPA cases are depicted according to approximate time publication became available (preprint or publication), except as indicated (*). BAL, bronchioalveolar lavage; CAPA, coronavirus disease–associated pulmonary aspergillosis; ECMO, extracorporeal membrane oxygenation; EU, European Union; ICU, intensive care unit; IL-6, interleukin 6.

Figure 3

Schematic of coronavirus disease–associated pulmonary aspergillosis. Aspergillus conidia in airway are cleared poorly because of ≥1 defects in primary pulmonary immunity or secondary defenses, enabling conidial germination into hyphal morphotypes, which elicit increased inflammatory responses in the airway and potential invasion into the lungs. A mixed constellation of inflammatory to invasive airway disease, and invasive pulmonary aspergillosis leads to multiple manifestations, including tracheobronchitis and obstructive pneumonia, and complications of invasive fungal pneumonia (nodules, necrosis with cavities, pleural invasion). A) Airways. Aspergillus overgrowth causes pathologic airway inflammation and excess mucous production. B) Alveoli. Hyphal growth causes invasive pneumonia. C) Invasive aspergillosis tracheobronchitis postobstructive bacterial pneumonia.