Invasive Cryptococcosis
COVID-19 patients with human immunodeficiency virus (HIV) infection accompanied by CD4 + T-lymphocyte count < 200 cells/μL, allo-HSCT, SOT, or other immune impaired are susceptible to cryptococcosis which predominantly present as meningoencephalitis [38]. Given the complexities surrounding the diagnosis of cryptococcosis and identification of Cryptococcus species including C. neoformans and C. gattii species, the diagnosis of cryptococcosis is usually based on a combination of clinical and laboratory confirmation. The methods used to confirm the infection are culture, direct microscopy, histopathology, serology, and molecular detection. To diagnose cryptococcosis, specimen from cerebrospinal fluid (CSF) can be mixed with India ink and observed under a microscope that the distinctive structure for Cryptococcus spp. with narrow budding encapsulated yeasts usually can be found. Samples for culture should be placed on Sabouraud dextrose agar at 30 °C for 7 days, in aerobic conditions, and observed daily. Moreover, cultures from patients receiving systemic antifungal therapy might need longer to grow. Cryptococcus appears as mucoid creamy colonies. Capsular polysaccharides of Cryptococcus can be detected and quantified from body fluids such as serum, CSF, BAL, or pathological tissue. Three formats of cryptococcal antigen (CrAg) detection tests are currently available: the latex agglutination test (LAT), the enzyme-linked immunoassay (EIA), and the lateral flow immunoassay (LFA). These methods are rapid, sensitive, and specific, but have not been standardized for respiratory specimens such as BAL, pleural fluid, or sputum [32]. Molecular detection of Cryptococcus is required in specific situations where other diagnostic tools have failed to confirm a diagnosis of cryptococcosis. These molecular methods include pan-fungal PCR, DNA sequencing for identification, multiplex PCR, isothermal amplification method, and probe-based microarrays. Once a diagnosis cryptococcosis is made, a lumbar puncture and cerebrospinal fluid (CSF) examination (including antigen) are recommended in all patients [39]. Cryptococcus can disseminate into the central nervous system causing cryptococcal meningitis.
The treatment recommendations can be supported by guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents, and children in 2018 by World Health Organization (from: https://www.who.int/hiv/pub/guidelines/cryptococcal-disease/en/). Generally, the following is recommended as the preferred regimen: (i) Induction phase for amphotericin B deoxycholate and + flucytosine, followed by fluconazole; alternative options for fluconazole + flucytosine or amphotericin B deoxycholate + fluconazole. (ii) Consolidation phase for fluconazole. (iii) Maintenance (or secondary prophylaxis) phase for fluconazole.