Clinical-immuno-inflammatory signature for Aspergillus–Mucorales co-infection in ICU patientsICU patients with co-infection show higher but not significant mortality

Frontiers in Medicine Published April 23, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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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.

Researchers looked at 93 critically ill patients in a single ICU to see if a clinical-immuno-inflammatory signature could help identify those with both Aspergillus and Mucorales infections, compared to patients with only Aspergillus. The study was observational and small, especially for the co-infection group, which had only 18 patients.

The main finding was that patients with the co-infection had a higher ICU mortality rate (72.2%) than those with only Aspergillus (53.3%). However, this difference did not reach statistical significance, meaning it could be due to chance. No safety issues were reported, as the study did not track adverse events.

The main reason to be careful is the study's limitations: it was retrospective, done at one hospital, and had a small sample size. These factors mean the results are uncertain and not practice-changing.

What readers should take from this is that co-infection may be associated with worse outcomes, but this study does not prove it causes higher mortality. More research is needed before any clinical decisions can be made.

What this means for you:

Co-infection may be linked to higher ICU death, but this small study did not prove a significant difference.

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

Clinical-immuno-inflammatory signature for Aspergillus–Mucorales co-infection in ICU patientsICU patients with co-infection show higher but not significant mortality

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