Diagnosis of Invasive Fungal Disease in Coronavirus Disease 2019

Approaches and Pitfalls

P. Lewis White


Curr Opin Infect Dis. 2021;34(6):573-580. 

In This Article

Diagnosis of Coronavirus Disease 2019-associated Pneumocystis Jirovecii Pneumonia

Despite the presence of risk for developing PcP, very few cases have been reported. Case reports describing PcP in COVID-19 are generally associated with underlying conditions (e.g. HIV infection, haematological malignancy) that already predispose the patient to PcP.[13] In such patients, differentiating PcP chest radiology from that of COVID-19 infection is difficult, with manifestations, such as ground glass opacification common to both diseases. Subsequently, to avoid a misdiagnosis, it is important to consider PcP, alongside COVID-19, as part of the initial differential diagnosis when screening high-risk populations presenting with chest infection during the pandemic.[53–55]

Definitive PCP diagnosis requires microscopic visualization of P. jirovecii in respiratory tract specimens and while immune-fluorescent microscopy improves sensitivity, it lacks the capacity to exclude PcP and interpretation remains subjective. The difficulty in culturing Pneumocystis precludes it from a diagnostic role.[56] PcP PCR performed on respiratory samples is a highly sensitive test, particularly when testing deeper respiratory samples (sensitivity >90%) but can detect potential Pneumocystis colonization/contamination of the respiratory tract rather than PcP in the COVID-19 patient, with a significant number of PcP PCR positive patients surviving despite the absence of PcP treatment.[57,58] Combining PcP PCR on respiratory samples with serum BDG (itself a very sensitive test for the diagnosis of PcP) can provide enhanced specificity when both tests are positive, and permits the PcP PCR testing of upper respiratory tract samples.[59,60] Using serum BDG alone for the diagnosis of PcP is not recommended for the reasons discussed previously, and while sensitivity is generally sufficient to exclude PcP when BDG is negative, performance outside of the HIV infected has shown reduced sensitivity, supporting a combined PcP PCR/BDG strategy. Incorporating testing of elevated serum lactate dehydrogenase, alongside PcP PCR and BDG may be useful and in a recent retrospective study, this strategy diagnosed PcP in 4/57 COVID-19 patients.[60]