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http://dx.doi.org/10.15324/kjcls.2021.53.3.201

C-Reactive Protein a Promising Biomarker of COVID-19 Severity  

Fazal, Muntaha (Department of Biomedical Laboratory Sciences, School of Health Sciences, University of Management and Technology)
Publication Information
Korean Journal of Clinical Laboratory Science / v.53, no.3, 2021 , pp. 201-207 More about this Journal
Abstract
The 2019 coronavirus outbreak poses a threat to scientific, societal, financial, and health resources. The complex pathogenesis of severe acute respiratory syndrome coronavirus centers on the unpredictable clinical progression of the disease, which may evolve abruptly and result in critical and life-threatening clinical complications. Effective clinical laboratory biomarkers that can classify patients according to risk are essential for ensuring timely treatment, and an analysis of recently published studies found cytokine storm and coagulation disorders were leading factors of severe COVID-19 complications. The following inflammatory, biochemical, and hematology biomarkers markers have been identified in COVID-19 patients; neutrophil to lymphocyte ratio, c-reactive protein, procalcitonin, urea, liver enzymes, lactate dehydrogenase, serum amyloid A, cytokines, d-dimer, fibrinogen, ferritin, troponin, creatinine kinase, and lymphocyte, leukocyte, and platelet counts. These factors are predictors of disease severity and some are involved in the pathogenesis of COVID-19. CRP is an acute-phase, non-specific serological biomarker of inflammation and infection and is related to disease severities and outcomes. In the present study, CRP levels were found to rise dramatically among COVID-19 patients, and our findings suggest CRP could be utilized clinically to predict COVID-19 prognosis and severity even before disease progression and the manifestation of clinical symptoms.
Keywords
COVID-19; C-reactive protein; Severity;
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1 Xu X, Yu MQ, Shen Q, Wang LZ, Yan RD, Zhang MY, et al. Analysis of inflammatory parameters and disease severity for 88 hospitalized COVID-19 patients in Wuhan, China. Int J Med Sci. 2020;17:2052-2062. https://doi.org/10.7150/ijms.47935   DOI
2 Wang L. C-reactive protein in the early stages of COVID-19. Med Mal infect. 2020;50:332-334. https://doi.org/10.1016/j.medmal.2020.03.007   DOI
3 Keddie S, Ziff O, Chou MKL, Taylor RL, Heslegrave A, Garr E, et al. Laboratory biomarkers associated with COVID-19 severity and management. Clin Immunol. 2020;221:108614. https://doi.org/10.1016/j.clim.2020.108614   DOI
4 Kwaan HC. Coronavirus disease 2019: The role of the fibrinolytic system from transmission to organ injury and sequelae. Semin Thromb Hemost. 2020;46:841-844. https://doi.org/10.1055/s-0040-1709996   DOI
5 Favaloro EJ, Lippi G. Recommendations for minimal laboratory testing panels in patients with COVID-19: potential for prognostic monitoring. Semin Thromb Hemost. 2020;46:379-382. https://doi.org/10.1055/s-0040-1709498   DOI
6 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145-148. https://doi.org/10.1016/j.cca.2020.03.022   DOI
7 Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020;58:1131-1134. https://doi.org/10.1515/cclm-2020-0198   DOI
8 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-847. https://doi.org/10.1111/jth.14768   DOI
9 Huang J, Cheng A, Kumar R, Fang Y, Chen G, Zhu Y, et al. Hypoalbuminemia predicts the outcome of COVID-19 independent of age and co-morbidity. J Med Virol. 2020;92:2152-2158. https://doi.org/10.1002/jmv.26003   DOI
10 Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020;81:e6-12. https://doi.org/10.1016/j.jinf.2020.04.00
11 Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Deng Y, et al. Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a systemic review and meta-analysis. Int J Infect Dis. 2020;96:131-135. https://doi.org/10.1016/j.ijid.2020.04.08   DOI
12 Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58:1116-1120. https://doi.org/10.1515/cclm2020-0188   DOI
13 Levi M, Thachil J. Coronavirus disease 2019 coagulopathy: disseminated intravascular coagulation and thrombotic microangiopathy-either, neither, or both. Semin Thromb Hemost. 2020;46:781-784. https://doi.org/10.1055/s-0040-1712156   DOI
14 Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93:250-256. https://doi.org/10.1002/jmv.26232   DOI
15 Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395: 1054-1062. https://doi.org/10.1016/S0140-6736(20)30566-3   DOI
16 Vuong NL, Le Duyen HT, Lam PK, Tam DTH, Vinh Chau NV, Van Kinh N, et al. C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study. BMC Med. 2020;18:35. https://doi.org/10.1186/s12916-020-1496-1   DOI
17 Hu R, Han C, Pei S, Yin M, Chen X. Procalcitonin levels in COVID-19 patients. Int J Antimicrob Agents. 2020;56:106051. https://doi.org/10.1016/j.ijantimicag.2020.106051   DOI
18 Sproston NR, Ashworth JJ. Role of C-Reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754   DOI
19 Bhardwaj N, Ahmed MZ, Sharma S, Nayak A, Anvikar AR, Pande V. C-reactive protein as a prognostic marker of Plasmodium falciparum malaria severity. J Vector Borne Dis. 2019;56:122-126. https://doi.org/10.4103/0972-9062.263727   DOI
20 Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370. https://doi.org/10.1016/j.jcv.2020.104370   DOI
21 Ahnach M, Zbiri S, Nejjari S, Ousti F, Elkettani C. C-reactive protein as an early predictor of COVID-19 severity. J Med Biochem. 2020;39:500-507. https://doi.org/10.5937/jomb0-27554   DOI
22 Stringer D, Braude P, Myint PK, Evans L, Collins JT, Verduri A, et al. The role of C-reactive protein as a prognostic marker in COVID-19. Int J Epidemiol. 2021;50:420-429. https://doi.org/10.1093/ije/dyab012   DOI
23 Mueller AA, Tamura T, Crowley CP, DeGrado JR, Haider H, Jezmir JL, et al. Inflammatory biomarker trends predict respiratory decline in COVID-19 patients. Cell Rep Med. 2020;1:100144. https://doi.org10.1016/j.xcrm.2020.100144   DOI
24 Chen W, Zheng KI, Liu S, Yan Z, Xu C, Qiao Z. Plasma CRP level is positively associated with the severity of COVID-19. Ann Clin Microbiol Antimicrob. 2020;19:18. https://doi.org/10.1186/s12941-020-00362-2   DOI
25 Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. J Clin Lab Anal. 2020;34:e23618. https://doi.org/10.1002/jcla.23618   DOI
26 Du Clos TW. Function of C-reactive protein. Ann Med. 2000; 32:274-278. https://doi.org/10.3109/07853890009011772   DOI
27 de Souza Pires-Neto O, da Silva Graca Amoras E, Queiroz MAF, Demachki S, da Silva Conde SR, Ishak R, et al. Hepatic TLR4, MBL and CRP gene expression levels are associated with chronic hepatitis C. Infect Genet Evol. 2020;80:104200. https://doi.org/10.1016/j.meegid.2020.104200   DOI
28 Yamada T, Wakabayashi M, Yamaji T, Chopra N, Mikami T, Miyashita H, et al. Value of leukocytosis and elevated C-reactive protein in predicting severe coronavirus 2019 (COVID-19): A systematic review and meta-analysis. Clin Chim Acta. 2020;509: 235-243. https://doi.org/10.1016/j.cca.2020.06.008   DOI
29 Tan C, Huang Y, Shi F, Tan K, Ma Q, Chen Y, et al. C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol. 2020;92:856-862. https://doi.org/10.1002/jmv.25871.   DOI
30 Wang G, Wu C, Zhang Q, Wu F, Yu B, Lv J, et al. C-reactive protein level may predict the risk of COVID-19 aggravation. Open Forum Infect Dis. 2020;7:ofaa153. https://doi.org/10.1093/ofid/ofaa153   DOI
31 Lau ES, McNeill JN, Paniagua SM, Liu EE, Wang JK, Bassett IV, et al. Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: insights from the MGH COVID-19 patient registry. PLoS One. 2021;16:e0250774. https://doi.org/10.1371/journal.pone.0250774   DOI
32 Laguna-Goya R, Utrero-Rico A, Talayero P, Lasa-Lazaro M, Ramirez-Fernandez A, Naranjo L, et al. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020;146:799-807.e9. https://doi.org/10.1016/j.jaci.2020.07.009   DOI
33 Aksel G, Islam MM, Algin A, Eroglu SE, Yasar GB, Ademoglu E, et al. Early predictors of mortality for moderate to severely ill patients with Covid-19. Am J Emerg Med. 2021:45:290-296. https://doi.org/10.1016/j.ajem.2020.08.076   DOI
34 Poggiali E, Zaino D, Immovilli P, Rovero L, Losi G, Dacrema A, et al. Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients. Clin Chim Acta. 2020; 509:135-138. https://doi.org/10.1016/j.cca.2020.06.012   DOI
35 Shang W, Dong J, Ren Y, Tian M, Li W, Hu J, et al. The value of clinical parameters in predicting the severity of COVID-19. J Med Virol. 2020;92:2188-2192. https://doi.org/10.1002/jmv.26031   DOI
36 Liu SL, Wang SY, Sun YF, Jia QY, Yang CL, Cai PJ, et al. Expressions of SAA, CRP, and FERR in different severities of COVID-19. Eur Rev Med Pharmacol Sci. 2020;24:11386-11394. https://doi.org/10.26355/eurrev_202011_23631   DOI
37 Bergantini L, Bargagli E, d'Alessandro M, Refini RM, Cameli P, Galasso L, et al. Prognostic bioindicators in severe COVID-19 patients. Cytokine. 2021;141:155455. https://doi.org/10.1016/j.cyto.2021.155455   DOI
38 Xue G, Gan X, Wu Z, Xie D, Xiong Y, Hua L, et al. Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19. Int Immunopharmacol. 2020; 89:107065. https://doi.org/10.1016/j.intimp.2020.107065   DOI
39 Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med. 2020;8:497. https://doi.org/10.21037/atm.2020.03.157   DOI
40 Thachil J, Srivastava A. SARS-2 coronavirus-associated hemostatic lung abnormality in COVID-19: is it pulmonary thrombosis or pulmonary embolism? Semin Thromb Hemost. 2020;46:777-780. https://doi.org/10.1055/s-0040-1712155   DOI
41 World Health Organization. Pneumonia of unknown cause-China [Internet]. WHO; 2020 [cited 2021, May 9]. Available from: https://www.who.int/csr/don/05-january-2020-peumonia-of-unkown-cause-china/en/
42 Li X, Marmar T, Xu Q, Tu J, Yin Y, Tao Q, et al. Predictive indicators of severe COVID-19 independent of comorbidities and advanced age: a nested case-control study. Epidemiol Infect. 2020;148:e255. https://doi.org10.1017/S0950268820002502   DOI
43 Wang Z, Wang Z. Identification of risk factors for in-hospital death of COVID - 19 pneumonia -lessions from the early outbreak. BMC Infect Dis. 2021;21:113. https://doi.org/10.1186/s12879-021-05814-4   DOI
44 Smilowitz NR, Kunichoff D, Garshick M, Shah B, Pillinger M, Hochman JS, et al. C-reactive protein and clinical outcomes in patients with COVID-19. Eur Heart J. 2021;42:2270-2279. https://doi.org/10.1093/eurheartj/ehaa1103   DOI
45 Liu YP, Li GM, He J, Liu Y, Li M, Zhang R, et al. Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study. Ann Transl Med. 2020;8:635. https://doi.org/10.21037/atm-20-2372   DOI
46 Schulman S. Coronavirus disease 2019, prothrombotic factors, and venous thromboembolism. Semin Thromb Hemost. 2020; 46:772-776. https://doi.org/10.1055/s-0040-1710337   DOI
47 Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18:1023-1026. https://doi.org/10.1111/jth.14810   DOI
48 Han Y, Zhang H, Mu S, Wei W, Jin C, Tong C, et al. Lactate dehydrogenase, an independent risk factor of severe COVID-19 patients: a retrospective and observational study. Aging (Albany NY). 2020;12:11245-11258. https://doi.org/10.18632/aging.103372   DOI
49 Akbari H, Tabrizi R, Lankarani KB, Aria H, Vakili S, Asadian F, et al. The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Life Sci. 2020;258:118167. https://doi.org/10.1016/j.lfs.2020.118167   DOI
50 Kushner I, Rzewnicki D, Samols D. What does minor elevation of c-reactive protein signify? Am J Med. 2006;119:166.e17-28. https://doi.org/10.1016/j.amjmed.2005.06.057   DOI
51 Ullah W, Thalambedu N, Haq S, Saeed R, Khanal S, Tariq A, et al. Predictability of CRP and D-Dimer levels for in-hospital outcomes and mortality of COVID-19. J Community Hosp Intern Med Perspect. 2020;10:402-408. https://doi.org/10.1080/20009666.2020.1798141   DOI
52 Sadeghi-Haddad-Zavareh M, Bayani M, Shokri M, Ebrahimpour S, Babazadeh A, Mehraeen R, et al. C-reactive protein as a prognostic indicator in COVID-19 patients. Interdiscip Perspect Infect Dis. 2021;2021:5557582. https://doi.org/10.1155/2021/5557582   DOI