Co-infection with influenza A(H1N1) and A(H3N2) correlates with increased hypoxemia

Overview

This retrospective single-center study examined whether detection of both influenza A(H1N1) and A(H3N2) during the same hospital admission identified a high-risk phenotype among adults with influenza-associated community-acquired pneumonia (CAP). Dual positivity was associated with worse hypoxemia, greater inflammatory activation, more fungal co-detection, increased invasive ventilation, and more adverse hospital dispositions than H1N1 mono-positivity.

Background

Influenza-associated CAP is an important cause of acute hypoxemic respiratory failure, intensive care admission, and in-hospital death among adults. Dual-subtype positivity is biologically plausible but uncommon and may reflect true coinfection, sequential infection with overlapping viral shedding, or a high-viral-burden state. Because the study documented co-detection during the same admission without viral-load measurements or genomic confirmation, it could not establish simultaneous coinfection.

Data Highlights

• Adults included: 97

• H1N1 mono-positive patients: 51

• H1N1/H3N2 dual-positive patients: 46

• Median PaO2/FiO2: 244.17 with dual positivity vs 293.94 with mono-positivity

• Fungal co-detection: 47.8% vs 25.5%

• Invasive mechanical ventilation: 23.9% vs 7.8%

• Composite adverse hospital disposition: 26.1% vs 3.9%

• In-hospital mortality: 15.2% vs 3.9%

Key Findings

• Dual-positive patients had significantly worse oxygenation and higher C-reactive protein and interleukin-6 levels.

• Fungal co-detection was more frequent in the dual-positive group and was driven primarily by Pneumocystis jirovecii detection.

• Bacterial co-detection did not differ significantly between the groups.

• Dual positivity was associated with greater use of invasive mechanical ventilation.

• The age- and sex-adjusted association between dual positivity and composite adverse hospital disposition attenuated after PaO2/FiO2 was added to the model.

• In-hospital mortality was numerically higher among dual-positive patients, but the difference was not statistically significant.

Clinical Implications

H1N1/H3N2 dual positivity may serve as an exploratory marker of more severe influenza-associated CAP. The findings support cautious, oxygenation-centered and microbiologically vigilant assessment. However, detected organisms should be interpreted in their clinical context because fungal co-detection did not establish invasive disease, and dual influenza positivity did not confirm simultaneous coinfection. The study did not evaluate specific antiviral, antimicrobial, or antifungal treatment strategies.

Conclusion

Detection of both H1N1 and H3N2 during the same admission was associated with worse hypoxemia, greater inflammatory burden, more invasive ventilation, increased fungal co-detection, and a higher burden of adverse hospital disposition. Oxygenation was the principal clinical correlate of excess risk. Larger multicenter studies with serial virologic sampling, genomic confirmation, standardized fungal evaluation, precise sampling and treatment timelines, and postdischarge follow-up are needed.

Related Resources & Content

1. Dual-Subtype Positivity of Influenza A(H1N1) and A(H3N2) Is Associated With Worse Hypoxemia, Fungal Co-Detection, and Adverse Short-Term Outcomes in Adults With Influenza-Associated Community-Acquired Pneumonia — Li Q, Li H, Fan L, et al. International Journal of Infectious Diseases. 2026;171:108985. doi:10.1016/j.ijid.2026.108985.

2. Severity of Clinical Presentation and Outcomes in Hospitalized Adult People With Influenza by Type and Subtype, United States—2017–2020 — Cleary S, Lewis NM, Talbot HK, et al. Clinical Infectious Diseases. 2025;82(3):e580–e588.

3. Review of Influenza-Associated Pulmonary Aspergillosis in ICU Patients and Proposal for a Case Definition: An Expert Opinion — Verweij PE, Rijnders BJA, Brüggemann RJM, et al. Intensive Care Medicine. 2020;46(8):1524–1535.

4. Deep Sequencing Reveals Mixed Infection With 2009 Pandemic Influenza A(H1N1) Virus Strains and the Emergence of Oseltamivir Resistance — Ghedin E, Fitch A, Boyne A, et al. Journal of Infectious Diseases. 2011;203(2):168–174.