• Blanca Valenzuela-Méndez, Francisco Valenzuela-Sánchez, Juan Francisco Rodríguez-Gutiérrez, Rafael Bohollo-de-Austria, Ángel Estella, Pilar Martínez-García, María Ángela González-García, Grant Waterer, and Jordi Rello.
• Gynecology and Obstetrics Department, Hospital Municipal de Badalona, Spain. Universitat Autonòma de Barcelona, Barcelona, Spain.
• Eur. J. Intern. Med. 2022 Oct 1; 104: 89-97.

BackgroundLimited knowledge exists on how early host response impacts outcomes in influenza pneumonia.MethodsThis study assessed what was the contribution of host immune response at the emergency department on hospital mortality amongst adults with influenza A H1N1pdm09 pneumonia and whether early stratification by immune host response anticipates the risk of death. This is a secondary analysis from a prospective, observational, multicenter cohort comparing 75 adults requiring intensive care with 38 hospitalized in medical wards. Different immune response biomarkers within 24 h of hospitalization and their association with hospital mortality were assessed.ResultsFifty-three were discharged alive. Non-survivors were associated (p<0.05) with lower lymphocytes (751 vs. 387), monocytes (450 vs. 220) expression of HLA-DR (1,662 vs. 962) and higher IgM levels (178 vs. 152;p<0.01). Lymphocyte subpopulations amongst non-survivors showed a significantly (p<0.05) lower number of TCD3+ (247.2 vs. 520.8), TCD4+ (150.3 vs. 323.6), TCD8+ (95.3 vs. 151.4) and NKCD56+ (21.9 vs. 91.4). Number of lymphocytes, monocytes and NKCD56+ predicted hospital mortality (AUC 0.854). Hospital mortality was independently associated with low HLA-DR values, low number of NKCD56+ cells, and high IgM levels, in a Cox-proportional hazard analysis. A second model, documented that hospital mortality was independently associated with a phenotype combining immunoparalysis with hyperinflammation (HR 5.53; 95%CI 2.16-14.14), after adjusting by predicted mortality.ConclusionsWe conclude that amongst influenza pneumonia, presence of immunoparalysis was a major mortality driver. Influenza heterogeneity was partly explained by early specific host response dysregulations which should be considered to design personalized approaches of adjunctive therapy.Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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