Identifying IFI risk factors in patients with COVID-19

IFIs can complicate the clinical course of COVID-19

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). 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). A narrative review found that IFIs were present in approximately 7% of patients with COVID-19.¹ Importantly, a meta-analysis found that CAPA and CAM were associated with a 75.2% and 13% mortality rate in patients diagnosed with COVID-19, respectively.²

Risk factors for COVID-19-associated IFIs

It remains unknown if SARS-CoV-2 infection is an independent risk factor for IFIs.³ However, patients with COVID-19 often have multiple known risk factors for IFIs, including in-dwelling vascular catheters, mechanical ventilation, and the use of broad-spectrum antibiotics.¹ Additionally, treatments for COVID-19 – which regulate the inflammatory response – may also increase the risk of IFIs.⁴ One study found that chronic corticosteroid treatment was substantially more frequent in patients with CAPA, especially in those who did not survive, compared with non-infected patients.³

Furthermore, many patients infected with CAM who did not have traditional risk factors often had either hypertension or end-stage renal failure, and had received corticosteroid treatment for COVID-19.⁴ In fact, one retrospective study in India found 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.⁵

Table 1. Risk factors for CAPA, CAM and other IFIs in patients with COVID-19⁴

Risk factors	CAPA	CAM	Other IFIs
ICU, mechanical ventilation + clinical deterioration	✔️	✔️	✔️
IL-6 inhibitor therapy	✔️
Immunosuppressive therapy	✔️	✔️	✔️
Poorly controlled diabetes		✔️
Major trauma		✔️	✔️

Drugs category	Drugs	Mechanism	IFIs
Immune modulators	Corticosteroids	↓ vasodilation, permeability of capillaries & leukocyte migration ↓ neutrophil apoptosis & demargination	Aspergillosis Mucormycosis
Monoclonal antibodies			Not reported yet

CAPA, COVID-19-associated pulmonary aspergillosis; CAM, COVID-19-associated mucormycosis; IFI, invasive fungal infections
Adapted from Basile K, et al. J Fungi 2022 

Conclusion

An increasing number of observational studies have shown that the clinical course of COVID-19 can be complicated by various IFIs (particularly CAPA and CAM), leading to increased morbidity and mortality, especially among critically ill patients. In the absence of antifungal prophylaxis, screening of COVID-19 patients for IFIs is essential to reduce delays in diagnosis and treatment to help prevent severe illness and death from these infections.⁶

References

1. Casalini G, et al. J Fungi (Basel) 2021;7:921.
2. Sah SK, et al. PLoS One 2022;17(7):e0271795.
3. Koehler P, et al. Lancet Infect Dis 2021;21: e149–62.
4. Basile K, et al. J Fungi 2022;8:58.
5. Patel A, et al. Emerg Infect Dis 2021;27:2349–2359
6. CDC – Fungal Diseases and COVID-19