Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital
Felix Eduardo R Punzalan, Jaime Alfonso M Aherrera, Sheriah Laine M De Paz-Silava, Alric V Mondragon, Anna Flor G Malundo, Joanne Jennifer E Tan, Ourlad Alzeus G Tantengco, Elgin Paul B Quebral, Mary Nadine Alessandra R Uy, Ryan C V Lintao, Jared Gabriel L Dela Rosa, Maria Elizabeth P Mercado, Krisha Camille Avenilla, Jonnel B Poblete, Albert B Albay, Aileen S David-Wang, Marissa M Alejandria
Frontiers in Immunology, doi:10.3389/fimmu.2023.1123497
Purpose: This study was performed to determine the clinical biomarkers and cytokines that may be associated with disease progression and in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to severe COVID-19 infection from October 2020 to September 2021, during the first wave of COVID-19 pandemic before the advent of vaccination. Patients and methods: Clinical profile was obtained from the medical records. Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and procalcitonin) and serum concentrations of cytokines (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-g, IP-10, TNF-a) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the onset of illness. Regression analysis was done to determine the association of the clinical laboratory biomarkers and cytokines with the primary outcomes of disease progression and mortality. ROC curves were generated to determine the predictive performance of the cytokines. Results: We included 400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on admission. Disease progression occurred in Frontiers in Immunology frontiersin.org 01
Ethics statement This study was approved by the UP Manila Research Ethics Board (UPMREB 2020-251-01). The patients/participants provided their written informed consent to participate in this study.
Author contributions Conceptualization: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, AD-W, and MA. Methodology: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, MM, KA, JP, AD-W, and MA. Formal analysis: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, MM, KA, AA, AD-W, and MA. Investigation: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, MM, KA, AD-W, and MA. Resources: FP, SP-S, and MA. Data curation: JA, SP-S, JT, OT, EQ, MU, RL, JR, MM, KA, and JP. Writingoriginal draft preparation: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, and MM. Writingreview & editing: FP, JA, SP-S, AMo, AMa, OT, MM, and MA. Supervision: FP, JA, SP-S, AMo, AMa, AD-W, and MA. Project administration: FP, JA, SP-S, AD-W, and MA. Funding acquisition: FP, JA, SP-S, AMo, AMa, JT, OT, EQ, MU, RL, JR, AD-W, and MA. All authors contributed to the article and approved the submitted version.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any..
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'abstract': '<jats:sec><jats:title>Purpose</jats:title><jats:p>This study was performed to determine the '
'clinical biomarkers and cytokines that may be associated with disease progression and '
'in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to '
'severe COVID-19 infection from October 2020 to September 2021, during the first wave of '
'COVID-19 pandemic before the advent of '
'vaccination.</jats:p></jats:sec><jats:sec><jats:title>Patients and '
'methods</jats:title><jats:p>Clinical profile was obtained from the medical records. '
'Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and '
'procalcitonin) and serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, '
'IL-18, IFN-γ, IP-10, TNF-α) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the '
'onset of illness. Regression analysis was done to determine the association of the clinical '
'laboratory biomarkers and cytokines with the primary outcomes of disease progression and '
'mortality. ROC curves were generated to determine the predictive performance of the '
'cytokines.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We included '
'400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on '
'admission. Disease progression occurred in 139 (35%) patients, while 18% of the total cohort '
'died (73 out of 400). High D-dimer &gt;1 µg/mL (RR 3.5 95%CI 1.83–6.69), elevated LDH '
'&gt;359.5 U/L (RR 1.85 95%CI 1.05–3.25), lymphopenia (RR 1.91 95%CI 1.14–3.19), and '
'hypoalbuminemia (RR 2.67, 95%CI 1.05–6.78) were significantly associated with disease '
'progression. High D-dimer (RR 3.95, 95%CI 1.62–9.61) and high LDH (RR 5.43, 95%CI 2.39–12.37) '
'were also significantly associated with increased risk of in-hospital mortality. Nonsurvivors '
'had significantly higher IP-10 levels at 0 to 3, 4 to 10, and 11 to 14 days from illness '
'onset (<jats:italic>p&lt;</jats:italic>0.01), IL-6 levels at 0 to 3 days of illness '
'(<jats:italic>p</jats:italic>=0.03) and IL-18 levels at days 11-14 of illness '
'(<jats:italic>p</jats:italic>&lt;0.001) compared to survivors. IP-10 had the best '
'predictive performance for disease progression at days 0-3 (AUC 0.81, 95%CI: 0.68–0.95), '
'followed by IL-6 at 11-14 days of illness (AUC 0.67, 95%CI: 0.61–0.73). IP-10 predicted '
'mortality at 11-14 days of illness (AUC 0.77, 95%CI: 0.70–0.84), and IL-6 beyond 14 days of '
'illness (AUC 0.75, 95%CI: '
'0.68–0.82).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Elevated '
'D-dimer, elevated LDH, lymphopenia and hypoalbuminemia are prognostic markers of disease '
'progression. High IP-10 and IL-6 within the 14 days of illness herald disease progression. '
'Additionally, elevated D-dimer and LDH, high IP-10, IL-6 and IL-18 were also associated with '
'mortality. Timely utilization of these biomarkers can guide clinical monitoring and '
'management decisions for COVID-19 patients in the Philippines.</jats:p></jats:sec>',
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'title': 'Utility of laboratory and immune biomarkers in predicting disease progression and mortality '
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