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C-Reactive Protein a Promising Biomarker of COVID-19 Severity
Korean J Clin Lab Sci 2021;53:201-207  
Published on September 30, 2021
Copyright © 2021 Korean Society for Clinical Laboratory Science.

Muntaha Fazal

Department of Biomedical Laboratory Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
Correspondence to: Muntaha Fazal
Department of Biomedical Laboratory Sciences, University of Management and Technology, C-II Block C 2 Phase 1 Johar Town, Lahore, Punjab 54770, Pakistan
E-mail: muntahafazal1997@gmail.com
ORCID: https://orcid.org/0000-0002-2475-9420
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
INTRODUCTION

In December 2019, several pneumonia cases of unexplained etiology erupted in Wuhan city, China [1]. The causative pathogen now recognized as a novel coronavirus (nCoV), which was later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus is now known as the major cause of coronavirus disease 2019 (COVID-19), a predominantly respiratory illness with adverse clinical outcomes [2].

Many COVID-19 patients do not exhibit signs or symptoms, or just mild symptoms. However, a subgroup of patients has suffered a severe illness, which often progressed into critical illness. Severe COVID-19 can be regarded as having a cytokine storm, multiorgan disease and disruption of numerous physiological pathways encompassing fibrinolysis and hemostasis [3-7].

Anomalies in several inflammatory, hematological and biochemical biomarkers have been observed in severe COVID-19 patients which can be utilized further for earlier identification of COVID-19 severity as well as to monitor adverse outcomes, mortality and prognosis of COVID-19 patients. The vital role of abnormal laboratory parameters in patients with COVID-19 has lately become apparent, and published studies recommend that particular clinical laboratory parameters may help in risk stratification and prog-nosis of these patients, ultimately leading to earlier interventions and the achievement of desired clinical outcomes [8-15].

Hence, early recognition and timely intervention of COVID-19 are crucial factors to prevent adverse clinical outcomes and burden on the scarce health resources due to the admission of a large number of patients in intensive care units. By incorporating these clinical laboratory biomarkers in routine testing, limited medical resources can be allocated to those COVID-19 patients who require urgent and timely treatment especially in the areas of epidemic origin.

In this short review, we focused more on C-reactive protein (CRP) and its correlation to COVID-19 severity as CRP levels found to be escalated in severe COVID-19 patients which is greatly associated with the severity of disease and disease progression.

MAIN ISSUE

1. Clinical distribution of COVID-19 patients

COVID-19 patients can range from mild to critical illness according to their clinical status.

1)Mild patients: general symptoms (fever, cough, nausea, loss of smell and taste), no respiratory symptoms, no abnormal chest findings.

2)Moderate patients: SpO2 >94% and an indication of abnormal chest x-ray and respiratory function.

3)Severe patients: SpO2 <94%, respiratory rate more than 30 breaths/min, PaO2/FiO2 <300 mm Hg, lung infiltrates more than 50%, require nasal cannula and high flow oxygen.

4)Critically ill patients: Acute distress respiratory syndrome, septic shock, cytokine storm, multiorgan failure intensive care unit is needed.

2. Laboratory biomarkers in severe COVID-19 patients

Abnormalities in several hematological, biochemical and inflammatory biomarkers have been observed in COVID-19 patients with serious illness compared with a mild disease, which provide clinicians with justification for inclusion of these biomarkers in risk stratification models. These biomarkers act as an important tool to detect patients who are on the verge of developing severe disease even before the mani-festation of clinical symptoms in those epidemic areas which have limited health resources to carry out expensive laboratory and radiological examinations on COVID-19 patients. The CRP, albumin, LDH (lactate dehydrogenase), neutrophil to lymphocytes ratio, lym-phocytes count, procalcitonin, albumin, thrombocytes and ferritin can be used to determine the severity of COVID-19. Decline in lymphocyte, thrombocytes, albumin, and increase in CRP, NLR (neutrophil-lymphocyte ratio), procalcitonin, D-Dimer, ferritin has been reported in COVID-19 patients [10, 15-22].

3. C-reactive protein

C-reactive protein is a pentameric acute-phase protein and acute pneumococcal pneumonia. CRP shows raised expression during inflammatory diseases such as some cardiovascular diseases, rheumatoid arthritis and somehow involved in their pathogenesis. C-reactive protein is synthesized predominantly in hepatocytes but also by other cell types such as adi-pocytes, lymphocytes, endothelial cells, macrophages, and smooth muscle cells. CRP levels can rise up to 1000 folds in any bacterial infection and decline abruptly as soon as infection resolves.

Recently published studies have recommended that CRP is not just a biomarker of infection and inflam-mation but it is also an important mediator of inflammatory processes. CRP exists in two unique isoforms, native CRP (nCRP) and monomeric, or modified CRP (mCRP), and the nCRP isoform has the ability to break down irreversibly into five mCRP subunits at sites of infection, inflammation and tissue damage. CRP acts as both pro-inflammatory and anti-inflammatory molecules depending upon which isoform of CRP is being released and active during infection and inflammation. CRP exhibits anti-inflam-matory effects by mediating the activation of the complement pathway, apoptosis, phagocytosis, and pro-inflammatory effects by nitric oxide (NO) release and cytokine production [23].

CRP plays a critical role in the recognition of self and foreign molecules. This interaction leads to an activation of the adaptive immune system in inflammatory or infectious diseases. CRP has an affinity towards phosphatidylcholine ligands present on damaged cell membranes; exposed and denatured chromatin and small nuclear ribonucleoproteins. CRP plays a signi-ficant role in the clearance of these molecules through interaction with the complement system and Fc receptors on phagocytic cells [24]. Therefore, it has been suggested that CRP acts as a scavenger which is significant in clearing damaged membranes, decayed nuclear material, and autoantigens. CRP acts as an opsonin and helps to eradicate pathogens by phago-cytosis through opsonization and activation of the classical complement pathway by which it protects organisms from infections.

Many studies have suggested CRP has been used as a prognostic biomarker in acute and chronic infections, including malaria, dengue, and hepatitis C [25-27]. On the other hand, mild elevation of CRP may or may not be clinically significant, depending upon the clinical condition of the patient. Clinical correlations must be taken into account while interpreting the CRP test results.

4. CRP and COVID-19 severity

1) IL-6 is the main inducer of CRP in COVID-19

Elevated levels of cytokines have been observed in COVID-19 patients, suggesting a cytokine storm [6] and exacerbating immune response towards viral infection in COVID-19 patients which is the crucial factor involved in the severity of COVID-19. Among them, IL-6 is the most significant cytokine which directly correlates with CRP levels in COVID-19 patients. The higher the level of IL-6, the greater the CRP in blood; Therefore, CRP as an indirect biomarker of IL-6 is sufficient and reliable to detect the severity of COVID-19 instead of measuring all cytokines in the body [28-30].

Measurement of CRP alone is the most practical tool to monitor disease outcomes in COVID-19 patients as it is obtainable, easy to interpret, and cost-effective rather than evaluating all cytokines which are costly as well as a time-consuming process and cannot be carried out in regions that do not have big setup to carry out complex prognostic tests.

2) CRP can predict the disease severity and outcomes in COVID-19 patients

CRP levels in COVID-19 patients can effectively predict disease severity, adverse outcomes, prognosis, and mortality. High CRP levels in COVID-19 patients at hospital admission indicate CRP can be utilized as an independent biomarker for earlier detection of disease severity [15, 31] as severe patients are more likely to have high CRP levels as compared to non-severe patients which indicate disease severity as well as the disease advancement [32]. High CRP levels in COVID-19 patients are strongly associated with the prognosis of COVID-19 which must be employed within the clinical practice to guide COVID-19 disease severity [33, 34].

Data published in recent studies suggest severe COVID-19 patients had high CRP levels relative to non-severe COVID-19 patients [31, 35-38], and similarly non-survivors had high CRP levels relative to survivors [39, 40], which indicates CRP levels in COVID-19 patients act as the best discriminator to distinguish severe patients from non-severe patients as well as non-survivors from survivors. High CRP levels in COVID-19 patients are strongly associated with mortality [41, 42] and its increasing levels are a risk factor for COVID-19 patients which is strongly associated with admission to ICU and death (Table 1).

CRP levels in mg/dL patients in severe, non-severe, survivor and non-survivor COVID-19 patients

Severe Non-severe
43.15a 10.05a
1.4a 0.39a
0.54a 0.35a
8.64a 0.34a
54.60a 12.30a
Non-survivors Survivors
12.05b 2.3b
19.4b 7.68b

aCRP levels in severe and non-severe patients which indicates that severe patients have high CRP levels as compared to non-severe [31, 35-38].

bCRP levels in non-survivors patients is high as compared to survivors [39, 40, 51].

After analysis of this data we can say although levels of CRP in mg/dL in severe, and non-survivor patients are vary in every publish article but these value are high in every article relative to non-severe and survivors and till now final threshold value to predict severe and non-survivors patients has not been decided yet.

Even in the absence of clinical history or radiological findings, we can anticipate COVID-19 outcomes by just looking at the CRP levels. Earlier detection of high CRP levels is the most appropriate method to detect COVID-19 patients, especially asymptomatic COVID-19 patients who are more vulnerable to develop severe disease. CRP can be used not only to monitor the prognosis of COVID-19 but also to discern severe patients from non-severe patients for risk stratification and better allocation of health services in areas that have reserved medical resources.

3) Combination of CRP with other biomarkers of severity in COVID-19

One of the striking features of CRP is it can be used in combination with other prognostic biomarkers to predict disease severity and published studies have recounted the fact that the predictive capacity of CRP was increased when it was combined with NLR, leukocytosis, serum amyloid A and ferritin to predict the prognosis of COVID-19 and vice versa. As patients with high NLR, leukocytosis, serum amyloid A and ferritin are more likely to develop severe disease so synergistic effect of CRP with these biomarkers can be used to improve the predictive capacity of CRP [34, 36, 43, 44]. Therefore, a complete panel of clinical biomarkers that are capable of detecting COVID-19 severity must be included in routine biochemical testing for earlier detection and timelier intervention of COVID-19 patients.

4) Correlation of CRP with computed tomography findings in severe COVID-19 patients

Rapid elevation of CRP in COVID-19 patients indicates aggressive immune response towards viral infection which is associated with lungs, kidney, and heart deterioration. The higher the initial CRP levels, the greater will be the pulmonary destruction and chances of having ARDS (acute respiratory distress syndrome). Thus, aggravated CRP in COVID-19 patients reflects lung destruction that should be regulated to prevent serious illness [44, 45]. Since the increase in CRP is positively correlated with pulmonary lesions, it can therefore be used along with the radiological findings to monitor disease progression. CRP is positively associated with the computed tomography (CT) grading score; CT scores increase as CRP increases, which makes it the best serological marker to monitor disease progression in an epidemic area having a massive number of COVID-19 patients but insufficient medical reserves for radiographic exami-nation [15, 46].

As the CRP is positively associated with exacerbating immune response to viral infection and lung damage which makes it an even more sensitive clinical indicator of disease severity rather than CT grading itself [45], given that changes in CRP levels occur before the onset of pulmonary damage that has marked the significance of measuring CRP levels over time to detect the outcome of the disease even before the worsening of clinical condition.

5) Dynamic trends in CRP is predictive of COVID-19 severity

Dynamic trends in CRP are the most appropriate method to monitor COVID-19 patients, as CRP levels continuously tend to rise in progressive patients who initially presented themselves as mild patients and later develop severe disease.

It has been demonstrated in a study that dynamic trends in CRP are the best predictor of disease severity rather than initial CRP levels in predicting respiratory decline during hospitalization in COVID-19 patients and the change in CRP retains superior predictive value to either initial CRP value or the ROX (respiratory rate oxygenation) indices [30], as with every 1 unit increase in CRP in COVID-19 patients there is an increase in likelihood to shift from mild to severe COVID-19 disease [47].

Hence, serial measurement of CRP must be taken into account while monitoring COVID-19 patients as it is a highly convenient method for clinicians compared to complicated scoring systems and has the robust prognostic ability to predict respiratory failure among initially mild patients.

6) CRP tend to be high in men as compared to women suffering from COVID-19

Many elements can modify baseline CRP levels including age, sex, smoking status, weight, lipid levels, and blood pressure [48], after adjusting the baseline CRP levels, it has been detected CRP levels tend to be high among men relative to women suffering from COVID-19 [49, 50].

Data in recently published studies related to COVID-19 has shown men are more inclined to develop the severe disease as compared to women. We can assume that it may be due to high CRP levels that men are more prone to develop severe forms as compared to women but what is the actual reason behind the high ratio of men in severe COVID-19 yet to be identified.

7) Increased CRP levels indicates need for mechanical ventilation in COVID-19 patients

High CRP levels due to increased IL-6 release strongly predicts the need for mechanical ventilation in COVID-19 patients [51, 52], which indicates the like-lihood of using CRP to guide treatment in COVID-19 patients who might need mechanical ventilation in future due to hyperinflammatory syndrome. That’s why, CRP must be regulated in COVID-19 patients to prevent adverse outcomes.

8) Limitations

In this short review article, we have not mentioned single cut-off value of CRP needed to predict COVID-19 severity and prognosis as it has not been decided by health organizations yet. Similarly, as research is still undergoing on biomarkers of COVID-19 severity till now not a single biomarker with high prognostic value has been selected and approved to detect COVID-19 severity.

CONCLUSION

C-reactive protein is a convenient, economical, and easy to obtain prognostic biomarker that links with the disease severity and mortality. This can be used as an aid in clinical practice to guide treatment and monitor the COVID-19 patients in adjunct with other clinical parameters of prognosis and diagnosis. By doing so, we can improve prognosis and underrate mortality rates. We can conclude from the analysis of recent studies that a complete laboratory score consists of hematological, inflammatory and biochemical parameters must be taken into account to predict the severity and prognosis of COVID-19 patients irrespective of their clinical status for risk stratification and optimal allocation of health resource especially in the areas of limited health resources to improve clinical management and prevention of serious complications.

Acknowledgements

None

Conflict of interest

None

Author’s information (Position)

Fazal M, Graduate student.

References
  1. 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/.
  2. 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.
    Pubmed KoreaMed CrossRef
  3. 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.
    Pubmed KoreaMed CrossRef
  4. 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.
    Pubmed KoreaMed CrossRef
  5. 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.
    Pubmed KoreaMed CrossRef
  6. 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.
    Pubmed KoreaMed CrossRef
  7. 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.
    Pubmed KoreaMed CrossRef
  8. 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.
    Pubmed KoreaMed CrossRef
  9. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu ZLiu 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.
    Pubmed KoreaMed CrossRef
  10. 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.
    Pubmed KoreaMed CrossRef
  11. Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi MLevi 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.
    Pubmed CrossRef
  12. Han H, Yang L, Liu R, Liu F, Wu KL, Li JLi 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/cclm-2020-0188.
    Pubmed CrossRef
  13. 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.
    Pubmed CrossRef
  14. 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.
    Pubmed KoreaMed CrossRef
  15. 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.
    Pubmed KoreaMed CrossRef
  16. Huang J, Cheng A, Kumar R, Fang Y, Chen G, Zhu YZhu 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.
    Pubmed KoreaMed CrossRef
  17. Han Y, Zhang H, Mu S, Wei W, Jin C, Tong CTong 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.
    Pubmed KoreaMed CrossRef
  18. Cheng L, Li H, Li L, Liu C, Yan S, Chen HChen H, et al. Ferritin in the coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. J Clin Lab Anal. 2020;34. https://doi.org/10.1002/jcla.23618.
    Pubmed KoreaMed CrossRef
  19. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHXWang 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.
    Pubmed KoreaMed CrossRef
  20. Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Deng YDeng 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.
    Pubmed KoreaMed CrossRef
  21. Akbari H, Tabrizi R, Lankarani KB, Aria H, Vakili S, Asadian FAsadian 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. https://doi.org/10.1016/j.lfs.2020.118167.
    Pubmed KoreaMed CrossRef
  22. Hu R, Han C, Pei S, Yin M, Chen X. Procalcitonin levels in COVID-19 patients. Int J Antimicrob Agents. 2020;56. https://doi.org/10.1016/j.ijantimicag.2020.106051.
    Pubmed KoreaMed CrossRef
  23. 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.
    Pubmed KoreaMed CrossRef
  24. Du Clos TW. Function of C-reactive protein. Ann Med. 2000;32:274-278. https://doi.org/10.3109/07853890009011772.
    Pubmed CrossRef
  25. 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.
    Pubmed CrossRef
  26. Vuong NL, Le Duyen HT, Lam PK, Tam DTH, Vinh Chau NV, Van Kinh NVan 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.
    Pubmed KoreaMed CrossRef
  27. de Souza Pires-Neto O, da Silva Graça Amoras E, Queiroz MAF, Demachki S, da Silva Conde SR, Ishak RIshak R, et al. Hepatic TLR4, MBL and CRP gene expression levels are associated with chronic hepatitis C. Infect Genet Evol. 2020;80. https://doi.org/10.1016/j.meegid.2020.104200.
    Pubmed CrossRef
  28. Li X, Marmar T, Xu Q, Tu J, Yin Y, Tao QTao Q, et al. Predictive indicators of severe COVID-19 independent of comorbidities and advanced age: a nested case-control study. Epidemiol Infect. 2020;148. https://doi.org10.1017/S0950268820002502.
    Pubmed KoreaMed CrossRef
  29. Liu F, Li L, Xu M, Wu J, Luo D, Zhu YZhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127. https://doi.org/10.1016/j.jcv.2020.104370.
    Pubmed KoreaMed CrossRef
  30. Mueller AA, Tamura T, Crowley CP, DeGrado JR, Haider H, Jezmir JLJezmir JL, et al. Inflammatory biomarker trends predict respiratory decline in COVID-19 patients. Cell Rep Med. 2020;1. https://doi.org10.1016/j.xcrm.2020.100144.
    Pubmed KoreaMed CrossRef
  31. 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.
    Pubmed KoreaMed CrossRef
  32. Sadeghi-Haddad-Zavareh M, Bayani M, Shokri M, Ebrahimpour S, Babazadeh A, Mehraeen RMehraeen R, et al. C-reactive protein as a prognostic indicator in COVID-19 patients. Interdiscip Perspect Infect Dis. 2021;2021. https://doi.org/10.1155/2021/5557582.
    Pubmed KoreaMed CrossRef
  33. Stringer D, Braude P, Myint PK, Evans L, Collins JT, Verduri AVerduri 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.
    Pubmed KoreaMed CrossRef
  34. Poggiali E, Zaino D, Immovilli P, Rovero L, Losi G, Dacrema ADacrema 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.
    Pubmed KoreaMed CrossRef
  35. Shang W, Dong J, Ren Y, Tian M, Li W, Hu JHu 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.
    Pubmed KoreaMed CrossRef
  36. Liu SL, Wang SY, Sun YF, Jia QY, Yang CL, Cai PJCai 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.
    Pubmed CrossRef
  37. Bergantini L, Bargagli E, d'Alessandro M, Refini RM, Cameli P, Galasso LGalasso L, et al. Prognostic bioindicators in severe COVID-19 patients. Cytokine. 2021;141. https://doi.org/10.1016/j.cyto.2021.155455.
    Pubmed KoreaMed CrossRef
  38. Xue G, Gan X, Wu Z, Xie D, Xiong Y, Hua LHua L, et al. Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19. Int Immunopharmacol. 2020;89. https://doi.org/10.1016/j.intimp.2020.107065.
    Pubmed KoreaMed CrossRef
  39. Aksel G, İslam MM, Algın A, Eroğlu SE, Yaşar GB, Ademoğlu EAdemoğlu 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.
    Pubmed KoreaMed CrossRef
  40. 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.
    Pubmed KoreaMed CrossRef
  41. Ullah W, Thalambedu N, Haq S, Saeed R, Khanal S, Tariq ATariq 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.
    Pubmed KoreaMed CrossRef
  42. Smilowitz NR, Kunichoff D, Garshick M, Shah B, Pillinger M, Hochman JSHochman 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.
    Pubmed KoreaMed CrossRef
  43. Liu YP, Li GM, He J, Liu Y, Li M, Zhang RZhang 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.
    Pubmed KoreaMed CrossRef
  44. Yamada T, Wakabayashi M, Yamaji T, Chopra N, Mikami T, Miyashita HMiyashita 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.
    Pubmed KoreaMed CrossRef
  45. Tan C, Huang Y, Shi F, Tan K, Ma Q, Chen YChen 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.
    Pubmed KoreaMed CrossRef
  46. Keddie S, Ziff O, Chou MKL, Taylor RL, Heslegrave A, Garr EGarr E, et al. Laboratory biomarkers associated with COVID-19 severity and management. Clin Immunol. 2020;221. https://doi.org/10.1016/j.clim.2020.108614.
    Pubmed KoreaMed CrossRef
  47. Wang G, Wu C, Zhang Q, Wu F, Yu B, Lv JLv J, et al. C-reactive protein level may predict the risk of COVID-19 aggravation. Open Forum Infect Dis. 2020;7. https://doi.org/10.1093/ofid/ofaa153.
    Pubmed KoreaMed CrossRef
  48. 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.
    Pubmed CrossRef
  49. Xu X, Yu MQ, Shen Q, Wang LZ, Yan RD, Zhang MYZhang 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.
    Pubmed KoreaMed CrossRef
  50. Lau ES, McNeill JN, Paniagua SM, Liu EE, Wang JK, Bassett IVBassett 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. https://doi.org/10.1371/journal.pone.0250774.
    Pubmed KoreaMed CrossRef
  51. Laguna-Goya R, Utrero-Rico A, Talayero P, Lasa-Lazaro M, Ramirez-Fernandez A, Naranjo LNaranjo 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.
    Pubmed KoreaMed CrossRef
  52. 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.
    Pubmed KoreaMed CrossRef

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