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

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  • 1 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
  • 2 Division of Pulmonary and Critical Care, Department of Medicine, Buddhasothorn Hospital, Chachoengsao, Thailand;
  • 3 Division of Pulmonary and Critical Care, Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
  • 4 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
  • 5 Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;
  • 6 Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Oxford University, Oxford, United Kingdom;
  • 7 Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Walailak University, Nakhon Si Thammarat, Thailand;
  • 8 Siriraj Hospital, Division of Critical Care, Department of Medicine, Faculty of Medicine, Mahidol University, Bangkok, Thailand;
  • 9 Hospital for Tropical Disease, Faculty of Tropical Medicine, Chonburi Hospital, Chonburi, Thailand;
  • 10 School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand

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.

Author Notes

Address correspondence to Chaisith Sivakorn, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok 10400, Thailand, E-mail: chaisith.siv@mahidol.edu or Tachpon Techarang, School of Medicine, Thasala, Nakhon Si Thammarat, 80161, Thailand, E-mail: g.tachpon@gmail.com.

Authors’ addresses: Chaisith Sivakorn, Clinical Tropical Medicine, Mahidol University Faculty of Tropical Medicine, Bangkok, Thailand, E-mail: chaisith.siv@mahidol.edu. Jutamas Dechsanga, Division of Pulmonary and Critical Care, Department of Medicine, Chonburi Hospital, Chonburi, Chonburi, Thailand, E-mail: kratair_medicine@hotmail.com. Lawan Jamjumrus and Patchrapa Wattanawinitchai, Division of Pulmonary and Critical Care, Department of Medicine, Buddhasothorn Hospital, Chachoengsao, Chachoengsao, Thailand, E-mails: lawanpang@gmail.com and ptchrpk@gmail.com. Kobporn Boonnak, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Salaya, Nakhon Pathom, Thailand, E-mail: kobporn.boo@mahidol.ac.th. Marcus J. Schultz, Intensive Care Unit, AMC, Amsterdam, Amsterdam, The Netherlands, E-mail: marcus.j.schultz@gmail.com. Arjen M. Dondorp, Mahidol–Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Bangkok, Thailand, E-mail: arjen@tropmedres.ac. Weerapong Phumratanaprapin and Tanaya Siripoon, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mails: weerapong.phu@mahidol.ac.th and tanaya.sir@mahidol.edu. Ranistha Ratanarat, Faculty of Medicine, Mahidol University, and Siriraj Hospital, Department of Medicine, Bangkok, Thailand, E-mail: ranittha@hotmail.com. Thummaporn Naorungroj, Mahidol University, Siriraj Hospital, Salaya, Nakhon Pathom, Thailand, E-mail: thummaporn.nao@mahidol.ac.th. Chatnapa Duangdee, Hospital for Tropical Disease, Mahidol University, Salaya, Nakhon Pathom, Thailand, E-mail: chatnapa.dua@mahidol.ac.th. Tachpon Techarang, School of Medicine, Walailak University, Thai Buri, Nakhon Si Thammarat, Thailand, E-mail: g.tachpon@gmail.com.

Financial support: The publication of this work was granted by Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Disclosure: The study protocol was reviewed and approved by the institutional review boards of the local ethics committees of Chonburi Hospital (129/63/S/h3) and Buddhasothorn Hospital (BSH-IRB 043/2563). The data that support the findings of this study are available from Chonburi and Buddhasothorn Hospital, but restrictions apply to their availability of these data and so are not publicly available. However, data are available from the authors upon reasonable request and with the permission of the institution.

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