Invasive Aspergillosis (IA)
Aspergillus species could be an important cause of life-threatening infection in COVID-19 patients, especially in those with high risk factors. The potential risk factors for the patients include GC use, prolonged neutropenia, chronic obstructive pulmonary disease (COPD), allogeneic hematopoietic stem cell transplant (allo-HSCT) [26], solid organ transplant (SOT) [27], inherited immunodeficiencies, hemopoietic malignancy (HM), cystic fibrosis (CF) [28], etc. The diagnosis of IA requires a microbiologic and/or histopathologic evidence, although specimen acquisition is challenging in many patients because lung biopsy might be contraindicated in patients with coagulation disorders or severe respiratory failure [13]. Histopathologic examination mainly rely on finding special fungal stains on lung fluid or tissue when a fungal infection is suspected and may reveal the characteristic acute angle branching septate hyphae of Aspergillus spp., and Grocott-Gomori’s methenamine-silver stain (GMS) and periodic acid-Schiff (PAS) stains of fixed tissue will helpful, while it is difficult to distinguish Aspergillus spp. from other filamentous fungi such as Fusarium spp. and Scedosporium spp. [29]. Therefore, it is necessary to have a definitive confirmation by culture or nonculture technique, including (i) direct microscopic examination with the optical brightener methods, Calcofluor or Blankophor, which may increase the sensitivity and specificity for detecting Aspergillus-like features; (ii) culture on fungal-specific media at 37 °C for 2–5 days, if positive, morphological features of Aspergillus can be identified under the microscope or the DNA sequencing may be used in reference laboratories to identify the species accurately, but usually culture yield is low and a negative result does not exclude the diagnosis of IA; (iii) molecular assays targeting ribosomal DNA (rDNA) sequences can also be used for detection of Aspergillus in tissues or BALF, especially PCR-based assays can be used to detect Aspergillus spp. and CYP51A resistance mutations in A. fumigatus, although these methods have not been standardized or limited by laboratory conditions or proven commercial reagents in some countries [30]; (iv) serum and BALF GM testing are also recommended as an early and accurate marker using less invasive techniques for the diagnosis, especially in neutropenic patients, with advantages of less injury and time-efficient, though sometimes this test in blood samples are less sensitive than cultures of respiratory samples [25].
The treatment recommendations can be supported by the 2016 Update guideline by the Infectious Diseases Society of America that the prophylaxis, therapeutic medication, combined, and alternative medication of aspergillus infection have been given more detailed guidance opinions [30]. Generally, drugs recommended for the treatment and prophylaxis of IA include triazoles (itraconazole, voriconazole, posaconazole, esaconazole), Amphotericin B and its liposomes and echinococcins (micafungin or carpofenjing). Most patients can choose triazole drugs to treat IA, however, therapeutic drug monitoring (TDM) is recommended and the interaction between azoles and other drugs should be fully considered.