High Mobility Group Box 1 and Interleukin 6 at Intensive Care Unit Admission as Biomarkers in Critically Ill COVID-19 Patients.

Chaisith Sivakorn,Marcus J Schultz,Thummaporn Naorungroj,Chatnapa Duangdee,Jutamas Dechsanga,Patchrapa Wattanawinitchai,Tachpon Techarang,Lawan Jamjumrus,Arjen M Dondorp,Tanaya Siripoon,Weerapong Phumratanaprapin,Kobporn Boonnak,Ranistha Ratanarat

doi:10.4269/ajtmh.21-0165

Abstract

.Exuberant inflammation manifesting as a “cytokine storm” has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO2/FiO2 < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.

Highlights

Coronavirus disease 2019 (COVID-19) has emerged as a major threat worldwide, affecting more than 140 million people and resulting in more than 3 million deaths worldwide as of early April 2021.1 The clinical course of COVID-19 varies substantially among patients
After adjustment for age, gender and comorbidities by multivariate analysis, higher levels of plasma high mobility group box 1 protein (HMGB1) and IL-6 at intensive care unit (ICU) admission were not independently associated with ICU mortality (Supplemental Table 4). Within this cohort of severe COVID-19 patients admitted in ICU, HMGB1, and IL-6 plasma concentrations measured at ICU admission were highest in patients with a fatal course of the disease
Plasma concentrations of these biomarkers were higher in patients with a worse Sequential Organ Failure Assessment (SOFA) score (> 10), septic shock, or Acute kidney injury (AKI) and were associated with poor respiratory outcomes, including longer times on invasive mechanical ventilator (> 7 days) and a worse PaO2/FiO2 (< 150)

Summary

Introduction

Coronavirus disease 2019 (COVID-19) has emerged as a major threat worldwide, affecting more than 140 million people and resulting in more than 3 million deaths worldwide as of early April 2021.1 The clinical course of COVID-19 varies substantially among patients. Most infected individuals remain asymptomatic or exhibit only mild to moderate symptoms; approximately 15% progress to severe pneumonia, and up to 5% may eventually need admission to the intensive care unit (ICU) due to acute respiratory distress syndrome (ARDS), shock, or multiple organ failure.[2] A previous study suggested a scoring system (COVID-GRAM) predicting progress to critical illness, including admission to the ICU, requirement of invasive ventilation, and death in hospitalized COVID19 patients.[3] Including inflammatory mediators might improve the prognostic models because of their central role in the pathogenesis of severe COVID-19. Exuberant inflammation manifesting as elevated levels of cytokines, commonly referred as a “cytokine storm” has been suggested to lead to critical conditions, such as ARDS, multiorgan failure, and eventually death.

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