Plasma Levels of Mid-Regional Proadrenomedullin Accurately Identify H1N1pdm09 Influenza Virus Patients with Risk of Intensive Care Admission and Mortality in the Emergency Department

Blanca Valenzuela-Méndez; Francisco Valenzuela-Sánchez; Juan Francisco Rodríguez-Gutiérrez; Rafael Bohollo-de-Austria; Ángel Estella; Pilar Martínez-García; María Ángela González-García; Jordi Rello

doi:10.3390/jpm12010084

Plasma Levels of Mid-Regional Proadrenomedullin Accurately Identify H1N1pdm09 Influenza Virus Patients with Risk of Intensive Care Admission and Mortality in the Emergency Department

J Pers Med. 2022 Jan 10;12(1):84. doi: 10.3390/jpm12010084.

Authors

Blanca Valenzuela-Méndez¹, Francisco Valenzuela-Sánchez^{2

3}, Juan Francisco Rodríguez-Gutiérrez³, Rafael Bohollo-de-Austria², Ángel Estella^{2

4}, Pilar Martínez-García⁵, María Ángela González-García⁶, Jordi Rello^{7

8}

Affiliations

¹ Gynecology and Obstetrics Department, Hospital Municipal de Badalona, Universitat Autonòma de Barcelona, 08193 Barcelona, Spain.
² Critical Care Medicine Unit, University Hospital of Jerez, 11407 Jerez de la Frontera, Spain.
³ Hematology Department, University Hospital of Jerez, 11407 Jerez de la Frontera, Spain.
⁴ Department of Medicine Faculty, Medicine University of Cádiz, 11003 Cádiz, Spain.
⁵ Critical Care Medicine Unit, University Hospital Puerto Real, 11510 Puerto Real, Spain.
⁶ Department of Clinical Analysis, University Hospital of Jerez, 11407 Jerez de la Frontera, Spain.
⁷ CHRU Nîmes, 30900 Nimes, France.
⁸ Valld'Hebron Institut of Research, CIBERES, 08035 Barcelona, Spain.

Abstract

Early identification of severe viral pneumonia in influenza virus A (H1N1pdm09) patients is extremely important for prompt admission to the ICU. The objective is to evaluate the usefulness of MR-proadrenomedullin (MR-proADM) compared to C reactive protein (CRP), procalcitonin (PCT), and ferritin in the prognosis of influenza A pneumonia. This prospective, observational, multicenter study included one hundred thirteen patients with confirmed influenza virus A (H1N1pdm09) admitted to an Emergency Department and ICUs of six hospitals in Spain. Measurements and Main Results: one-hundred thirteen patients with confirmed influenza virus A (H1N1pdm09) were enrolled. Seventy-five subjects (mortality 29.3%) with severe pneumonia caused by influenza A H1N1pdm09 virus (H1N1vIPN) were compared with 38 controls (CG).The median MR-proADM levels at hospital admission were 1.2 nmol/L (IQR (0.8-2.6) vs. 0.5 nmol/L (IQR 0.2-0.9) in the CG (p = 0.01), and PCT levels were 0.43 μg/L (IQR 0.2-1.2) in the H1N1vIPN group and 0.1 μg/L (IQR 0.1-0.2) in the CG (p < 0.01). CRP levels at admission were 15.5 mg/dL(IQR 9.2-24.9) in H1N1vIPN and 8.6 mg/dL(IQR 3-17.3) in the CG (p < 0.01). Ferritin levels at admission were 558.1 ng/mL(IQR 180-1880) in H1N1vIPN and 167.7 ng/mL(IQR 34.8-292.9) in the CG (p < 0.01). A breakpoint for hospital admission of MR-proADM of 1.1 nmol/L showed a sensitivity of 55% and a specificity of 90% (AUC-ROC0.822). Non-survivors showed higher MR-proADM levels: median of 2.5 nmol/L vs. 0.9 nmol/L among survivors (p < 0.01). PCT, CRP, and ferritin levels also showed significant differences in predicting mortality. The MR-proADM AUC-ROC for mortality was 0.853 (p < 0.01). In a Cox proportional hazards model, MR-proADM levels > 1.2 nmol/L at hospital admission were significant predictive factors for ICU and 90-day mortality (HR: 1.3). Conclusions: the initial MR-proADM, ferritin, CRP, and PCT levels effectively determine adverse outcomes and risk of ICU admission and mortality in patients with influenza virus pneumonia. MR-proADM has the highest potency for survival prediction.

Keywords: CRP; H1N1 influenza pneumonia; ICU admission; MR proadrenomedullin; biomarkers; ferritin; procalcitonin; sepsis; virus.