Impact of the COVID-19 pandemic on IFI epidemiology and trends

The emergence of COVID-19 has resulted in rising incidence of invasive fungal infections (IFIs). Patients infected with COVID-19 often experience lung injury requiring admission to an ICU, where some will also receive treatment with steroids – known risk factors for fungal infection.¹ There is also the possibility that the virus and the complex immunopathology it induces may in some way predispose to fungal infections.² IFIs complicate the management of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients.³ Of note, the rising prevalence of IFIs in COVID-19 has led to new terms, such as COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM).¹

Since the start of the pandemic, CAPA has been the predominant fungal disease in patients with COVID-19 and acute respiratory distress syndrome.⁴ As mentioned, several immunological mechanisms may contribute to the development of CAPA in patients with COVID-19 infection. SARS-CoV-2 results in the release of danger-associated molecular patterns (DAMPs), which in turn exacerbate the inflammatory response leading to lung injury.⁴ Importantly, CAPA was significantly associated with mortality among intubated patients with COVID-19, with cohort studies consistently reporting mortality rates >40% among critically ill patients.^4-6

The COVID-19 pandemic has led to a resurgence of mucormycosis, particularly among patients with uncontrolled diabetes. Diabetes and hyperglycemia are often associated with an inflammatory state that could be aggravated by the immune response to SARS-CoV-2, which may lead to secondary infections.⁷ One retrospective study in India found that the prevalence of CAM increased 2.1-fold compared to the same period in 2019 before the pandemic.⁸ The study also reported that uncontrolled diabetes was the most common underlying disease among CAM and non-CAM patients. In 32.6% of patients presenting with CAM, COVID-19 was reported as their only underlying disease – with no other comorbidities – and up to 78.7% of them had received glucocorticoid treatment.⁸ Notably, inappropriate glucocorticoid use was independently associated with the development of late CAM. The mortality rate associated with mucormycosis was high and comparable for both CAM and non-CAM patients (44% vs 49%). Factors associated with a greater risk of mortality were older age, ICU admission, and pulmonary or brain involvement.⁸

In summary, COVID-19-associated IFIs pose a real threat to increasingly burdened healthcare systems, owing to increased hospitalization and mortality rates, or the utilization of existing resources. There is a need to improve awareness of such infections among healthcare professionals and formulate effective practical guidelines to optimize patient outcomes, while minimizing morbidity and mortality among patients.

References

1. Kundu R, Singla N. Current Fungal Infection Reports. 2022;16:47-54.
2. Arastehfar A, et al. J Fungi 2020;6:91
3. Casalini G, et al. J Fungi (Basel) 2021;7:921.
4. Hoenigl M. Clinical Infectious Diseases 2021;73:e1645-1648.
5. Koehler P, et al. Mycoses 2020;63:528-34.
6. Rutsaert L, et al. Ann Intensive Care 2020;10:71.
7. Hoenigl M, et al. Lancet Microbe 2022;3:e543-e552.
8. Patel A, et al. Emerg Infect Dis 2021;27:2349-59.