Based on a sample of 109 patients with confirmed influenza, we found that the incidence of IPA among patients hospitalized in non-ICU settings during the influenza season was 9.2%. The mortality rate for patients with IPA was 30%, higher than for patients without IPA. Out of 10 patients with IPA, seven improved, while three (30%) died. Patients with IPA were more likely to be transferred to the ICU compared to those without IPA. Additionally, the duration of hospital stay was longer than that of patients without IPA. Those IPA also had a higher incidence of underlying lung diseases. Furthermore, patients with probable IPA experienced significantly more bacterial co-infections than those without IPA. Patients admitted to the infectious disease ward included both immunocompetent and immunocompromised individuals.
The main distinction between our study and previous studies is that we focused on non-ICU patients with moderate influenza. The occurrence of IPA varied according to the severity of influenza and whether patients were transferred to the ICU or remained treated on medical wards [1].
A retrospective cohort study on invasive aspergillosis in patients admitted to the ICU with severe influenza found that immunocompromised patients had a higher mortality rate than immunocompetent patients (14% vs. 5%) [10]. Our study demonstrated similar results. A systematic review and meta-analysis involving 6,024 patients with severe IPA requiring ICU support reported an incidence rate of 10% for IPA, with a mortality rate of 52% [1]. Here we report a mortality rate among all patients with IPA was 30% which may reflect the lower patient numbers. In a retrospective bicentric cohort study involving 81 patients admitted to the ICU, 9 patients (11%) were diagnosed with invasive aspergillosis. The only identified risk factor was severe influenza infection. Patients with IPA who were admitted to the ICU required supportive therapies [12]. In our study, the incidence and mortality of IPA were similar. Risk factors included bacterial co-infection, underlying lung disease, and the length of hospitalization was consistent with other studies [1, 10, 12].
The cause of the recent rise in IPA is unclear [3]. Possible contributing factors include complications from treating patients with corticosteroids during the COVID-19 pandemic. Corticosteroid use is a risk factor for IPA and causes increased mortality [1, 14]. In addition, underlying lung diseases such as COPD, bronchiectasis and a history of pulmonary tuberculosis are also predisposing factors. A Swiss multicenter cohort study on IPA in critically ill influenza patients revealed that asthma and chronic lung disease were also risk factors for IPA [1, 5].
Exacerbations of COPD and bronchiectasis are associated with systemic inflammation due to the immune dysregulation [15]– [16]. Mycobacterium tuberculosis is triggered by innate and adaptive immune response host and control of infection [17]. Future bronchoscopic studies are required to identify the precise abnormal host-pathogen interactions linking disease exacerbations with IPA.
Our study has some limitations including the low number of patients due to possibly missing the peak time for influenza infection, other confounding factors with IPA besides of aspergillus infection and the large number of patients referred from other hospitals to the Mashie Daneshvari Pulmonary Hospital. it clear that all of participants, even those admitted from different Hospitals, were admitted through the Emergency Department to our specialist hospital before being transferred to the infection wards at the same Hospital. Referral bias from Emergency Department is, therefore, unlikely to be an issue although we acknowledge that transfer from other Hospitals may introduce some bias.
IPA is a life threating disease, therefore vaccination of high-risk patients with influenza and the development of a rapid, noninvasive and readily available validated tool to diagnose IPA is required. Currently, bronchoscopy and bronchoalveolar lavage are effective methods for diagnosing IPA. This approach is essential, within clinical settings, to provide direct evidence with high sensitivity for detecting Aspergillus species. To date, no validated test for the rapid diagnosis of IPA has been developed and molecular methods for influenza virus detection in BALF need to be performed.
The role of prophylaxis antifungal or treatment of fungal infection should be assessed in a prospective clinical trial. Accordingly, prophylactic treatment may have an important role in preventing fungal infections particularly in patients with weakened immune systems such as those with cancer and those who are immunocompromised patients [18, 19].