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 Mucormycosis

CAM has emerged as a somewhat unexpected, yet devastating complication of COVID-19, with diagnosis complicated by the prolonged period of presentation (0–90 days) post COVID-19 infection, including patients who have recovered from COVID-19, coupled with the limited testing options to diagnose this IFD.[14] As with other IFD, proven CAM can only be diagnosed by positive histology/microscopy demonstrating broad ribbon like hyphae with limited or no septa and 90° branching angles or positive culture of tissue biopsies or from other sterile sites.[8,14] Positive culture from respiratory tract samples (sputum, BAL fluid and tracheal aspirates) and sinus washout combined with radiology indicative of sinusitis or chest infection (nodules, reverse halo, cavities) is indicative of rhino-orbital/rhino-orbital-cerebral and pulmonary CAM, respectively. The primary presentation of CAM appears to be rhino-orbital-cerebral disease, with pulmonary disease generally presenting in patients with existing underlying conditions (e.g. haematological malignancy) that predispose to mucormycosis. Molecular testing of respiratory samples and serum may assist in the diagnosis of CAM, and can be used to aid in the identification of fungi in positive histology specimens where culture is negative. Unfortunately, the performance of Mucorales PCR is not validated for CAM, and given the wide array of species capable of causing mucormycosis may not be able to detect all causative agents. Pan-fungal PCR, with downstream processing (e.g. DNA sequencing) to provide at least a genus level identification should be used when testing positive tissue samples, although will delay the time to result. With most cases of CAM caused by Rhizopus species, which are usually detected by Mucorales PCR assays, this technology could play a significant role in the diagnosis of CAM, although positive culture is required for antifungal susceptibility testing.[14] Given the limited diagnostic options available for the diagnosis of Mucormycosis, likely exacerbated in resource limited settings and the poor sensitivity of conventional diagnostic approaches, many cases of CAM in high-risk areas (e.g. India) have been diagnosed on clinical presentation and individual underlying risk or discovered on autopsy.[14]