Eur J Intern Med
. 2022 Jul 30;S0953-6205(22)00259-X.
doi: 10.1016/j.ejim.2022.07.010. Online ahead of print.
Host response dysregulations amongst adults hospitalized by influenza A H1N1 virus pneumonia: A prospective multicenter cohort study
Blanca Valenzuela-Méndez 1 , Francisco Valenzuela-Sánchez 2 , Juan Francisco Rodríguez-Gutiérrez 3 , Rafael Bohollo-de-Austria 4 , Ángel Estella 5 , Pilar Martínez-García 6 , María Ángela González-García 7 , Grant Waterer 8 , Jordi Rello 9
Affiliations
- PMID: 35918257
- DOI: 10.1016/j.ejim.2022.07.010
Abstract
Background: Limited knowledge exists on how early host response impacts outcomes in influenza pneumonia.
Methods: This 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.
Results: Fifty-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.
Conclusions: We 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.
Keywords: Community-acquired pneumonia; Ferritin, Immunoparalysis; Precision medicine; Sepsis.