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..
References
Abani, Abbas, Abbas, Abbas, Abbasi et al., Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial, Lancet,
doi:10.1016/S0140-6736(21)00676-0Abou-Ismail, Diamond, Kapoor, Arafah, Nayak, The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management, Thromb Res,
doi:10.1016/J.THROMRES.2020.06.029Buja, Wolf, Zhao, Akkanti, Mcdonald et al., The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other united states cities, Cardiovasc Pathol Off J Soc Cardiovasc Pathol,
doi:10.1134/S0006297920100065Chen, Wang, Liu, Su, Zhang et al., IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19, Mol Med,
doi:10.1186/S10020-020-00230-XChen, Zhao, Qu, Chen, Xiong et al., Detectable serum severe acute respiratory syndrome coronavirus 2 viral load (RNAemia) is closely correlated with drastically elevated interleukin 6 level in critically ill patients with coronavirus disease 2019, Clin Infect Dis,
doi:10.1093/CID/CIAA449Chen, Zhou, Dong, Qu, Gong et al., Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, China: a descriptive study, Lancet,
doi:10.1016/S0140-6736(20)30211-7Coutinho, Oliveira, Albuquerque, Mota, Meneses et al., Elevated IL-18 predicts poor prognosis in critically ill COVID-19 patients at a Brazilian hospital in 2020-21, Future Microbiol,
doi:10.2217/FMB-2022-0057Cruz, Mendes-Frias, Oliveira, Dias, Matos et al., Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia, Front Immunol,
doi:10.3389/FIMMU.2021.613422Ejaz, Alsrhani, Zafar, Javed, Junaid et al., COVID-19 and comorbidities: Deleterious impact on infected patients, J Infect Public Health,
doi:10.1016/j.jiph.2020.07.014Goligher, Bradbury, Mcverry, Lawler, Berger et al., Therapeutic anticoagulation with heparin in critically ill patients with covid-19, BioMed Res Int,
doi:10.1155/2014/893106Gong, Dong, Xia, Huang, Dk et al., Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: A retrospective study, BMC Infect Dis,
doi:10.1186/S12879-020-05681-5Gorham, Moreau, Corazza, Peluso, Ponthieux et al., IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study, J Allergy Clin Immunol,
doi:10.3390/IJMS20030649Guo, Wang, Xia, Shi, Chen et al., Cytokine signature associated with disease severity in COVID-19, J Allergy Clin Immunol,
doi:10.3389/FIMMU.2021.681516Hadjadj, Yatim, Barnabei, Corneau, Boussier et al., Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients, Science,
doi:10.1126/SCIENCE.ABC6027Han, Ma, Li, Liu, Zhao et al., Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors, Emerg Microbes Infect,
doi:10.1080/22221751.2020.1770129Herold, Jurinovic, Arnreich, Lipworth, Hellmuth et al., Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: An ex vivo study with implications for the pathogenesis of COVID-19, J Allergy Clin Immunol,
doi:10.1093/CID/CIAA410Horby, Lim, Emberson, Mafham, Bell et al., Dexamethasone in hospitalized patients with covid-19, N Engl J Med,
doi:10.1056/NEJMoa2021436Ichikawa, Kuba, Morita, Chida, Tezuka et al., CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin, Am J Respir Crit Care Med,
doi:10.1164/RCCM.201203-0508OCLampart, Zellweger, Bassetti, Tschudin-Sutter, Rentsch et al., Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections-a prospective cohort study, PloS One,
doi:10.1371/journal.pone.0269005Lawler, Goligher, Berger, Neal, Mcverry et al., Therapeutic anticoagulation with heparin in noncritically ill patients with covid-19, N Engl J Med,
doi:10.1056/NEJMoa2105911Li, Ye, Chen, Hu, Wang et al., Epidemiological and clinical characteristics of the first 500 confirmed COVID-19 inpatients in a tertiary infectious disease referral hospital in Manila, Philippines, Trop Med Health,
doi:10.1186/S41182-021-00340-0Liu, Li, Liu, Liang, Wang et al., Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine,
doi:10.15252/EMMM.202012421Liu, Tao, Wang, Yuan, Liu et al., Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease, Chin Med J (Engl),
doi:10.1097/CM9.0000000000000775Lq, Huang, Yq, Zp, Liang et al., COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis, J Med Virol,
doi:10.1002/JMV.25757Lu, Zhu, Tan, Zhou, Hu et al., Changes of serum IL-10, IL-1b, IL-6, MCP-1, TNF-a, IP-10 and IL-4 in COVID-19 patients, Int J Clin Pract,
doi:10.1111/IJCP.14462Lucas, Wong, Klein, Castro, Silva et al., Early differences in cytokine production by severity of coronavirus disease 2019, J Infect Dis,
doi:10.1093/INFDIS/JIAB005Lupieri, Smirnova, Solinhac, Malet, Benamar et al., Smooth muscle cells-derived CXCL10 prevents endothelial healing through PI3Kg-dependent T cells response, Cardiovasc Res,
doi:10.1093/CVR/CVZ122Malik, Patel, Mehta, Patel, Kelkar et al., Biomarkers and outcomes of COVID-19 hospitalisations: Systematic review and meta-analysis, BMJ Evidence-Based Med,
doi:10.1136/BMJEBM-2020-111536Malundo, Abad, Salamat, Sandejas, Planta et al., Clinical characteristics of patients with asymptomatic and symptomatic COVID-19 admitted to a tertiary referral centre in the Philippines, IJID Reg,
doi:10.1016/j.ijregi.2022.02.002Martha, Wibowo, Pranata, Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: A systematic review and meta-analysis
Middleton, He, Denorme, Campbell, Ng et al., Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19: The HEP-COVID randomized clinical trial, JAMA Intern Med,
doi:10.1001/jamainternmed.2021.6203Niu, Sareli, Mayer, Visbal, Sareli, Lymphopenia as a predictor for adverse clinical outcomes in hospitalized patients with COVID-19: A single center retrospective study of 4485 cases, J Clin Med,
doi:10.3390/JCM11030700Omland, Mills, Mueller, Care the SG on b of the EA for AC. cardiovascular biomarkers in COVID-19, Eur Hear J Acute Cardiovasc Care,
doi:10.1093/EHJACC/ZUAB037Ranieri, Rubenfeld, Thompson, Ferguson, Acute respiratory distress syndrome: The Berlin definition, JAMA,
doi:10.1001/JAMA.2012.5669Rizzi, Costanzo, Tonello, Matino, Casciaro et al., Prognostic markers in hospitalized COVID-19 patients: The role of IP-10 and creactive protein, Dis Markers,
doi:10.1155/2022/3528312Sabaka, Kosčǎĺováa, Straka, Hodosy, Liptaḱ et al., Role of interleukin 6 as a predictive factor for a severe course of covid-19: Retrospective data analysis of patients from a long-term care facility during covid-19 outbreak, BMC Infect Dis,
doi:10.1186/S12879-021-05945-8Sanyaolu, Okorie, Marinkovic, Patidar, Younis et al., Comorbidity and its impact on patients with COVID-19, SN Compr Clin Med,
doi:10.1007/s42399-020-00363-4Satışh, Hs, Yıldız, Hızel, Gulbahar et al., Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19, Int J Mol Sci,
doi:10.3390/IJMS22157914Segundo, De Las Revillas, Lamadrid-Perojo, Comins-Boo, Gonzaĺez-Rico et al., Innate and adaptive immune assessment at admission to predict clinical outcome in COVID-19 patients, Biomedicines,
doi:10.3390/BIOMEDICINES9080917Shi, Wang, Ye, Gu, Wang et al., Predictors of mortality in patients with coronavirus disease 2019: A systematic review and meta-analysis, BMC Infect Dis,
doi:10.1186/S12879-021-06369-0Wang, Li, Yin, Zhang, Cao et al., Excessive neutrophils and neutrophil extracellular traps in COVID-19, Front Immunol,
doi:10.3389/fimmu.2020.02063Wu, Chen, Cai, Xia, Zhou et al., Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, China, JAMA Intern Med,
doi:10.1001/JAMAINTERNMED.2020.0994Xu, Yang, Wang, Li, Xue et al., Serum albumin levels are a predictor of COVID-19 patient prognosis: Evidence from a single cohort in chongqing, China, Int J Gen Med,
doi:10.2147/IJGM.S312521Yang, Shen, Li, Yuan, Wei et al., Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID
Zhan, Chen, Liu, Cheng, Yan et al., Diagnostic value of d-dimer in COVID-19: A meta-analysis and meta-regression, Clin Appl Thromb Hemost,
doi:10.1177/10760296211010976Zhang, Wang, Jia, Li, Hu et al., Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in wuhan, China, Clin Microbiol Infect,
doi:10.47895/amp.v54i0.1561Zhou, Fu, Zheng, Wang, Zhao et al., Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients, Natl Sci Rev,
doi:10.1093/NSR/NWAA041Zhou, He, Liang, Wang, Yu et al., Association of interleukin-6 levels with morbidity and mortality in patients with coronavirus disease 2019 (COVID-19), Jpn J Infect Dis,
doi:10.7883/YOKEN.JJID.2020.463Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in wuhan, China: A retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3
