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Host response dysregulations amongst adults hospitalized by influenza A H1N1 virus pneumonia: A prospective multicenter cohort study

      Highlights

      • Host immune response is crucial determining outcomes amongst patients with influenza pneumonia.
      • Hyper-inflammation (using ferritin as surrogate) was associated with increased ICU admission amongst adults hospitalized by influenza.
      • Hospital mortality was restricted to immune-paralysis (down-regulation of HLA-DR).
      • Early stratification of influenza pneumonia by immune-phenotypes may anticipate risk of death, and identify candidates for immunomodulation.

      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

      Abbreviations:

      APACHE II (acute physiology and chronic health evaluation II), AUC-ROC (area under the curve - receiver operating characteristic), CRP (C reactive protein), CRRT (continuous renal replacement therapy), Ct (cycle threshold), FiO2 (fraction of inspired oxygen), H1N1pdm09 (influenza virus A), H1N1vIPN (severe pneumonia caused by influenza A), HLA-DR (Human leucocyte Antigens-DR), ED (emergency department), ICU (intensive care unit), IQR (interquartile range), MR-proADM (MR-proadrenomedullin), MV (mechanical ventilation), PaO2 (arterial partial pressure of oxygen), PMN (polymorphonuclear neutrophils), PCT (procalcitonin), PIRO (Predisposition Infection Response Organ), SAPS II (simplified acute physiology score), SD (standard deviation), SOFA (sequential organ failure assessment)
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