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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