Background: Dual-subtype influenza A positivity is poorly characterized. We evaluated whether detection of A(H1N1) and A(H3N2) during the same admission identifies a high-risk phenotype in adults hospitalized with influenza-associated community-acquired pneumonia.

Methods: This retrospective single-center study linked clinical and bronchoalveolar lavage fluid pathogen-spectrum records. Influenza A was detected by RT-PCR and BALF pathogens by targeted next-generation sequencing. The primary endpoint was composite adverse hospital disposition (in-hospital death or discharge against medical advice [DAMA]); components were reported separately. Associations were estimated with binomial generalized linear models and Firth sensitivity analyses.

Results: Among 97 adults (51 H1N1 mono-positive; 46 dual-positive), dual positivity was associated with lower PaO2/FiO2 (244.17 vs 293.94; p=0.018), higher CRP and IL-6, more invasive ventilation (23.9% vs 7.8%; p=0.047), and more fungal co-detection (47.8% vs 25.5%; p=0.034). Composite adverse disposition occurred in 26.1% versus 3.9% (OR 8.65; p=0.003); the age- and sex-adjusted OR was 8.24 (p=0.010) and attenuated after PaO2/FiO2 adjustment (OR 4.38; p=0.147). In-hospital death was 15.2% versus 3.9% (p=0.081).

Conclusions: Dual positivity identified a severe hypoxemic phenotype with greater fungal co-detection. Oxygenation was the principal clinical correlate of excess risk.