Clinical-immuno-inflammatory signature for Aspergillus–Mucorales co-infection in ICU patients

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Frontiers in Medicine Published April 23, 2026 Medically reviewed April 24, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider the non-significant mortality association in this small ICU cohort when evaluating early co-infection signatures.

This was a single-center, retrospective observational cohort study conducted in an intensive care unit (ICU) setting. The population included 93 critically ill patients, with a focus on those with Aspergillus infection or Aspergillus–Mucorales co-infection. The study evaluated a clinical-immuno-inflammatory signature for early identification of co-infection, comparing it to a sole Aspergillus infection group.

The primary outcome was ICU mortality. The co-infection group exhibited substantially higher ICU mortality than the sole Aspergillus group, but the difference did not reach statistical significance. Absolute numbers were 72.2% mortality in the co-infection group versus 53.3% in the sole Aspergillus group, with a p-value of 0.24. No effect size was reported.

Safety and tolerability data were not reported for the intervention or exposure. The study had key limitations, including its retrospective design, single-center setting, and a small sample size for the co-infection group (n=18). The certainty of the evidence is low due to the retrospective design and non-significant result.

Practice relevance was not reported. The authors note this is an observational study; the findings show an association only, not causation. The mortality difference was not statistically significant, and the study does not establish causality.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

BackgroundCo-infection with Aspergillus and Mucorales in the intensive care unit (ICU) represents a devastating syndrome with high mortality that is frequently clinically occult. Clinically distinguishing this co-infection from invasive pulmonary aspergillosis (IPA) is challenging but critical for tailoring precise antifungal strategies.MethodsWe conducted a single-center, retrospective observational study involving 93 critically ill patients (75 with Aspergillus infection and 18 with co-infection) admitted between 2017 and 2025. We compared clinical characteristics, inflammatory markers, and immunophenotypes between groups. A three-stage variable selection strategy integrating univariable regression pre-screening, multi-algorithm importance ranking (LASSO, Ridge, and Random Forest), and clinical applicability filtering was employed to identify predictors for a multivariable logistic regression nomogram.ResultsThe co-infection group exhibited substantially higher ICU mortality than the sole Aspergillus group, although the difference did not reach statistical significance (72.2% vs. 53.3%, p = 0.24).Kaplan–Meier analysis demonstrated that initiation of amphotericin B within