Root Causes of Fungal Coinfections in COVID-19 Infected Patients

Abstract

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has infected over 200 million people, causing over 4 million deaths. COVID-19 infection has been shown to lead to hypoxia, immunosuppression, host iron depletion, hyperglycemia secondary to diabetes mellitus, as well as prolonged hospitalizations. These clinical manifestations provide favorable conditions for opportunistic fungal pathogens to infect hosts with COVID-19. Interventions such as treatment with corticosteroids and mechanical ventilation may further predispose COVID-19 patients to acquiring fungal coinfections. Our literature review found that fungal coinfections in COVID-19 infected patients were most commonly caused by Aspergillus, Candida species, Cryptococcus neoformans, and fungi of the Mucorales order. The distribution of these infections, particularly Mucormycosis, was found to be markedly skewed towards low- and middle-income countries. The purpose of this review is to identify possible explanations for the increase in fungal coinfections seen in COVID-19 infected patients so that physicians and healthcare providers can be conscious of factors that may predispose these patients to fungal coinfections in order to provide more favorable patient outcomes. After identifying risk factors for coinfections, measures should be taken to minimize the dosage and duration of drugs such as corticosteroids, immunosuppressants, and antibiotics.

Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics

“…The appearance of the COVID-19 pandemic has generated an increase in the diagnosis of some systemic mycoses such as aspergillosis and mucormycosis [ 27 ]; the latter has occurred with an unusually high frequency in India [ 28 ]. The occurrence of these mycoses has been favored by different factors or comorbidities associated with COVID-19, such as hypoxemia, diabetes mellitus, steroid use, increased ferritin and free serum iron levels, mechanical ventilation, and CD4 lymphopenia (total cells, CD4+ and CD8+).…”

“…The occurrence of these mycoses has been favored by different factors or comorbidities associated with COVID-19, such as hypoxemia, diabetes mellitus, steroid use, increased ferritin and free serum iron levels, mechanical ventilation, and CD4 lymphopenia (total cells, CD4+ and CD8+). However, only a handful of cases of cryptococcosis associated with COVID-19 have been described (two of them in the tropics), and no C. gattii infection has been reported [ 27 ].…”

Coccidioidomycosis and COVID-19 Infection. An Analysis from a Single Medical Center Within the Coccidioidal Endemic Area

“…Treatment often requires immunosuppressive medications, including corticosteroids. Because of these issues, patients with COVID-19 may be at risk for opportunistic respiratory infections, including those due to fungi [ 1 ].…”

Disseminated Cryptococcosis Complicating Severe SARS-CoV-2 Infection

“…Opportunistic invasive fungal infection in the setting of severe viral respiratory disease is a well-known condition described in the context of influenza, RSV, and now, COVID-19 [1]. The cytokine storm and immune dysregulation, leading to T-cell exhaustion, observed in COVID-19, may play a role increasing susceptibility to fungal infection development [1]. Specifically, Cryptococcus spp.…”