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

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.

Artificial Intelligence Predicts Severity of COVID-19 Based on Correlation of Exaggerated Monocyte Activation, Excessive Organ Damage and Hyperinflammatory Syndrome: A Prospective Clinical Study

“…Also, a recent study reported increased HMGB1 levels in serum of COVID-19 patients (63). The authors reported that at ICU admission, the plasma levels of HMGB1 and IL-6 correlated with D-dimer and C-reactive protein levels (28). However, in our study, despite a clear increase in HMGB1 levels in severe COVID-19, no correlation between HMGB1 and other parameters could be found.…”

“…HMGB1, one of the most extensively studied DAMPs, is correlated with the severity of tissue damage in patients with numerous lung disorders, including severe pneumonia (27). In a recent study, COVID-19 patients admitted to ICU had higher levels of HMGB1 compared to healthy controls (28). Several other damage molecules, such as LDH, AST and ALT, are often associated with multiorgan damage and might be used to estimate the severity of COVID-19 infection (29).…”

Factors Behind the Higher COVID-19 Risk in Diabetes: A Critical Review

“…Guo et al ( 25 ) report that, compared with non-DM patients, in DM individuals, the total absolute lymphocyte count in peripheral blood is greatly reduced, and the neutrophil absolute count shows a remarkable increase. Therefore, a high neutrophil–lymphocyte ratio (NLR) in DM patients may increase COVID-19 severity because high NLR is regarded as a poor prognostic factor linked to COVID-19 severity and mortality ( 109 ).…”

Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation

“…There are presently almost 200,000 publications about COVID-19 listed on PubMed but only 40 of them investigated the role of HMGB1, out of which only 4 reports on elevated systemic HMGB1 levels in COVID-19 patients [ 92 , 93 , 94 , 95 ]. This is a remarkably small number considering that extensive necrosis and hyperinflammation in the disease should generate substantial HMGB1 release.…”