Abstract
BACKGROUND: Allogenic hematopoietic stem cell transplantation (aHSCT) recipients are vulnerable to invasive fungal infections (IFI), a leading cause of morbidity and mortality. While known risk factors exist,(1,2) respiratory viral infections (RVIs) (e.g. influenza/COVID- 19-associated pulmonary aspergillosis in mechanically ventilated individuals)(3) are emerging as an independent risk factor post- aHSCT.(4,5) This study examines IFI incidence and its link to prior RVIs in aHSCT recipients. METHODS: This retrospective, single-centre study (IRCCS Humanitas Research Hospital, Milan, January 2018–February 2024) included all adult aHSCT recipients. The primary endpoint was IFI diagnosis per EORTC criteria.(6)The exposure variable was pre-IFI RVI diagnosis, defined by consistent clinical signs and positive viral PCR on respiratory specimens. Categorical variables were counts/frequencies; continuous: mean/SD or median/IQR. Logistic regression identified IFI predictors. Chi-squared/Fisher's exact tests compared categorical variables; Mann-Whitney U-test for continuous. Significant univariate covariates were included in a multivariable model to assess post-transplant IFI risk. RESULTS: Of 93 enrolled patients (156 hospitalizations), 27 IFIs were detected: incidence was 23.6% of patients and 17% of hospitalizations. 56% IFI patients had prior RVI, compared to 15/60 (25%, P = 0.019) with RVI and 4/8 (50%, P = 0.012) with RSV who later developed IFI. Patient characteristics are in Table 1. Median time from aHSCT to IFI was 201 (40–453) days (range: 6–1264); from RVI to IFI, 7 (0–24) days (range: 0–172). Multivariable analysis identified RSV infection, concomitant bacterial infection, and lower respiratory tract RVI as significant post-transplant IFI risk factors. Figure 1 explores IFI etiology, suggesting a possible (non-significant) link between pulmonary aspergillosis and RVI. CONCLUSIONS: In aHSCT patients, 24% developed IFI, 56% with prior RVI. 25% of RVI patients later developed IFI. Lower respiratory/RSV infections were associated with IFI.(4,7) Neutropenia wasn't an IFI risk factor,(1) possibly due to late-onset IFI, highlighting RVI's role. Limitations were small sample size and screening only symptomatic VRI. Despite this, strong evidence links RSV/lower respiratory infections with IFI, especially late post-transplant. [Table: see text] [Figure: see text]