The Impacts of Aspergillosis on Outcome, Burden and Risks for Mortality in Influenza Patients with Critical Illness

Abstract

Previous studies have revealed higher mortality rates in patients with severe influenza who are coinfected with invasive pulmonary aspergillosis (IPA) than in those without IPA coinfection; nonetheless, the clinical impact of IPA on economic burden and risk factors for mortality in critically ill influenza patients remains undefined. The study was retrospectively conducted in three institutes. From 2016 through 2018, all adult patients with severe influenza admitted to an intensive care unit (ICU) were identified. All patients were classified as group 1, patients with concomitant severe influenza and IPA; group 2, severe influenza patients without IPA; and group 3, severe influenza patients without testing for IPA. Overall, there were 201 patients enrolled, including group 1 (n = 40), group 2 (n = 50), and group 3 (n = 111). Group 1 patients had a significantly higher mortality rate (20/40, 50%) than that of group 2 (6/50, 12%) and group 3 (18/11, 16.2%), p < 0.001. The risk factors for IPA occurrence were solid cancer and prolonged corticosteroid use in ICU of >5 days. Group 1 patients had significantly longer hospital stay and higher medical expenditure than the other two groups. The risk factors for mortality in group 1 patients included patients' Charlson comorbidity index, presenting APACHE II score, and complication of severe acute respiratory distress syndrome. Overall, IPA has a significant adverse impact on the outcome and economic burden of severe influenza patients, who should be promptly managed based on risk host factors for IPA occurrence and mortality risk factors for coinfection with both diseases.

Keywords: aspergillosis; influenza; intensive care unit; mortality; outcome.

Figure 1

A total of 201 critically ill patients with positive testing for influenza were enrolled and were classified into three groups (A) and clinical outcome of group 1 (B) in real-world data from 2016 to 2018. Note. Flu, influenza assay; GM, galactomannan assay; (+), positive result; (-), negative result.

Figure 2

The overall survival using time-to-event analysis was lowest for group 1 of severely ill influenza patients with concomitant IPA among all three influenza groups (p = 0.071, (A)) with significant difference to group 2 with severe influenza only (p = 0.034, (B)). There was no significant difference between group 1 and group 3 (p = 0.551, (C)) and between group 2 and group 3 (p = 0.103, (D)). Note. Flu, influenza assay; GM, galactomannan assay; (+), positive result; (-), negative result.

Figure 3

A 64-year-old woman had a serum Aspergillus galactomannan test of 3.38 index and did not receive any antifungal therapy but experienced a prolonged course of more than 3 months for resolution of the bilateral pulmonary infiltrations.

Figure 4

A 48-year-old man had a serum Aspergillus galactomannan test of 1.24 index and did not receive any antifungal therapy but experienced a rapid course of resolution of the pulmonary infiltrates over the right lower lung field.