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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 19  |  Issue : 1  |  Page : 16-19

Biochemical and inflammatory parameters in intensive care unit and nonintensive care unit COVID-19 patients – A retrospective study


Department of Biochemistry, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India

Date of Submission12-Nov-2021
Date of Decision13-Jan-2022
Date of Acceptance14-Jan-2022
Date of Web Publication15-Feb-2022

Correspondence Address:
Suman Doddamani
Department of Biochemistry, Karnataka Institute of Medical Sciences, Vidyanagar, Hubli - 580 021, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_133_21

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  Abstract 


Background: COVID-19 presents with varied clinical presentations. Most of the patients have a good prognosis, but some patients rapidly progress to severe disease. Hence, early identification of severity becomes important. Aims and Objectives: This study aimed to compare the ferritin, troponin I, and D-dimer in intensive care unit (ICU) (severe) and non-ICU (nonsevere) patients of COVID-19. Materials and Methods: Data were collected from COVID-19 laboratory (n = approximately 2700). The patients were divided into ICU and non-ICU group. Ferritin and troponin I were estimated by chemiluminescence immunoassay and D-dimer was estimated by turbidimetric immunoassay. Results: Troponin I levels were comparable between the groups. Ferritin was elevated (P = 0.0001) in ICU patients compared to non-ICU patients. The levels of D-dimer were increased (P < 0.0001) in the ICU group compared to the non-ICU group. Conclusion: Despite the fact that troponin I may not be a decent indicator for the seriousness of the infection, it might be of use in patients with cardiovascular risk factors. Raised levels of ferritin might be a significant marker that demonstrates the chance of requiring escalated care for the COVID-19 patients. D-dimer can be used as a judicious marker for suggesting the severity and prognosis of the disease.

Keywords: COVID-19, D-dimer, ferritin, troponin I


How to cite this article:
Astagimath MN, Aryapu R, Doddamani S. Biochemical and inflammatory parameters in intensive care unit and nonintensive care unit COVID-19 patients – A retrospective study. Apollo Med 2022;19:16-9

How to cite this URL:
Astagimath MN, Aryapu R, Doddamani S. Biochemical and inflammatory parameters in intensive care unit and nonintensive care unit COVID-19 patients – A retrospective study. Apollo Med [serial online] 2022 [cited 2022 May 21];19:16-9. Available from: https://www.apollomedicine.org/text.asp?2022/19/1/16/337782




  Introduction Top


In December 2019, SARS-CoV-2 spread throughout China and rapidly spread to other countries of the world, resulting in a pandemic. Currently, the pathophysiology, epidemiology, and prognosis of COVID-19 are still not completely known. The main challenge faced by the treating physicians is the categorization of patients into mild, moderate, and severe diseases early in the course of the disease. Appropriate diagnostic markers play an important role in categorizing the patients. Hence, we planned to study the various laboratory parameters (ferritin, D-dimer, and troponin I) in patients with mild (nonintensive care unit [ICU]) and severe disease (ICU). The D-dimer is a degradation product of fibrin; it is a small protein fragment present in the blood after a blood clot is degraded. The elevation in circulating levels of D-dimer is a sensitive test used to diagnose thrombotic states, including disseminated intravascular coagulation and pulmonary embolism.[1] Troponin I is a regulatory protein that plays a role in regulating calcium-mediated interaction between actin and myosin. Ferritin is a major iron storage protein. It is a large protein that is present in both cytosol and mitochondria; predominantly, the cytosolic form is seen more often. This cytosolic ferritin has light (L) and heavy (H) subunits.[2] Some of the pro-inflammatory cytokines such as interleukin-6, interleukin-1, and tumor necrosis factor-alpha have been shown to transcriptionally induce the H chain of ferritin.[1],[3] Thus, elevated levels of ferritin act as an inflammatory marker. Many studies have shown the possibility of few laboratory markers, mainly lymphopenia and elevated D-dimer, correlating with deleterious outcomes.[4] However, the majority of these studies were done on a small sample and few studies were done from India. As the current study depends on a broad overview of a huge gathering of data from patients (total 7800 patients), the outcomes acquired from this investigation can be stretched out to the population at large.

Aims and objectives

This study aimed to compare the ferritin, troponin I, and D-dimer in ICU (severe) and non-ICU (nonsevere) patients of COVID-19.


  Materials and Methods Top


The study includes the laboratory data of patients who were admitted from May 2020 to October 2020 to Karnataka Institute of Medical Sciences, Hubballi, Karnataka, a tertiary care hospital for COVID-19 treatment. The patients were divided into two groups (1) those who were admitted to ICU (severe disease) and (2) those who were admitted in the wards (non-ICU) (mild disease). Coronavirus-positive babies, mothers, pregnant women, and patients whose total information was not accessible were avoided from the study. The parameters included in the study were ferritin, troponin I, and D-dimer. Ferritin and troponin I were estimated by chemiluminescence immunoassay and D-dimer was estimated by turbidimetric immunoassay. The reagents were procured from VITROS, Ortho Clinical diagnostics, 1500 Boulevard Sébastien Brant B.P. 30335 67411 Illkirch. CEDEX, France. Ethical committee permission was obtained from the institutional ethical committee (No. KIMS/EC/415/2020-21). Statistical analysis was done using SPSS and MedCalc software (IBM SPSS statistics ver.21).


  Results Top


In the severe group (ICU patients), patients over 50 years were more (approximately 3–4 times) [Table 1]. Severe COVID-19 was more in males (2.5 times) contrasted with females [Table 2]. Troponin I levels were comparable between the groups. Ferritin was elevated (P = 0.0001) in ICU patients compared to non-ICU patients. The levels of D-dimer were increased (P < 0.0001) in the ICU group compared to the non-ICU group [Table 3].
Table 1: Descriptive parameters in intensive care unit patients in the different age groups

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Table 2: Descriptive parameters in intensive care unit patients with respect to gender

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Table 3: Comparison of laboratory parameters among intensive care unit and nonintensive care unit patients

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  Discussion Top


The whole world is hit by the COVID-19 pandemic. A few laboratory parameters were found to be associated with COVID-19 illness. We estimated the laboratory parameters such asferritin, D-dimer, and troponin I. These markers assume a significant part in the clinical management of COVID-19.

An elevation in troponin I levels is normally seen in COVID-19 patients and is related to fatal outcomes.[5] Troponin I levels were comparable between the groups. This suggests that troponin I may not be a good marker for indicating the severity of the disease, but it may be of value in patients with cardiac comorbidities. Our findings were similar to a meta-analysis report published by Lippi G, which concluded that higher troponin I levels were seen in severe COVID-19 patients compared to those with milder COVID-19.[6] The research published by Gregorio Tersalvi concluded that increased troponin levels are frequently seen in patients with COVID-19 and associated with fatal outcomes. The mechanisms for increased troponin I, according to the author, are viral myocarditis, cytokine-driven myocardial damage, microangiopathy, and unmasked coronary artery disease.[5] Troponin I is reported to be elevated in sepsis and respiratory illness.[7],[8] The mechanism might be increased myocardial oxygen demand due to inflammation and also compromised oxygen supply to the myocardium due to respiratory illness. In COVID-19, the rise in the cytokines is said to favor suppression of angiotensin-converting enzyme-2,[9] which may cause direct and indirect injury to the myocardium. We stressed the fact that troponin I could be of use in patients with a high risk of developing cardiovascular disorders, this is supported by the fact that inflammation and viral invasion in COVID-19 may cause plaque instability.[5] Thus, even though troponin I may not be a good predictor for the severity of the disease, it may be of potential use in patients with cardiac comorbidities.

We found the levels of ferritin were elevated significantly (P = 0.0001) in ICU patients compared to the non-ICU patients. It was noted that irrespective of age and gender, an increase in ferritin can be a marker suggesting the severity of the disease [Table 3]. The above findings were similar to a study conducted by Bo Zhou, which was done on 20 patients, and the authors found significantly higher ferritin levels in very severe COVID-19 compared to the severe COVID-19 patients.[10] A meta-analysis conducted by Linlin Cheng showed similar findings in which around 18 studies were included and it was shown that ferritin was elevated in severe COVID-19 patients compared to the mild COVID-19 patients (397.77 95% confidence interval: 306.51–489.02), P < 0.001). The study also showed that nonsurvivors had a significantly higher ferritin level compared to survivors.[11] Elevated ferritin levels can be attributed to the hyperimmune response which is seen in severe COVID-19 disease. Studies suggest that massive cytokine release and uncontrolled inflammation are associated with severe COVID-19.[12] Elevated ferritin levels in COVID-19 may be due to the similarity of the pathogenesis of COVID-19 and macrophage activation syndrome (characterized by cytokine storm, immunological abnormalities, and hyperferritinemia).[13] Hence, we suggest that elevated levels of ferritin may be an important marker that indicates underlying uncontrolled inflammation and cytokine release and the possibility of requiring intensive care for the COVID-19 patients.

In this study, levels of D-dimer were significantly increased (P < 0.0001) in the ICU group compared to the non-ICU group. Similarly, statistically significant difference was found in males (P < 0.0001), females (P < 0.0001), patients below 50 years (P = 0.0051), and patients above 50 years (P < 0.0001). This suggests that D-dimer can be used as a predictive marker for suggesting the severity of the disease. Our findings were similar to a study conducted by Bansal et al. which concluded that COVID-19 patients who show increased D-dimer levels have worse outcomes in terms of ICU admission, ARDS, and mortality, and thus, measuring D-dimer can guide clinicians in decision-making.[14] Patel et al. studied 549 COVID-19 patients, of which 159 were admitted in ICU and it was found that D-dimer levels were higher in ICU patients compared to the non-ICU patients.[15] A review by Vidali et al. concluded that correlation exists between an elevation of D-dimer and severe COVID-19.[16] The inflammatory cytokines released during COVID-19 may result in an imbalance of fibrinolysis and coagulation in the alveoli; this may activate the fibrinolysis and thus increase in D-dimer levels.[17],[18]

The other findings of this study are as follows. In the severe group (ICU patients), patients over 50 years were more (approxiately 3–4 times). Severe COVID-19 was more in males (2.5 times) contrasted with females.


  Conclusion Top


Despite the fact that troponin I may not be a decent indicator for the seriousness of the infection, it might be of use in patients with cardiovascular risk factors. Raised levels of ferritin might be a significant marker that demonstrates the chance of requiring escalated care for the COVID-19 patients. D-dimer can be used as a judicious marker for suggesting the severity and prognosis of the disease.

Limitations

The COVID-19 patients on home isolation were excluded from this study. As this is a cross-sectional study, the laboratory parameters were estimated only on admission. Serial measurement of these parameters could yield better results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Olson JD. D-dimer: An overview of hemostasis and fibrinolysis, assays, and clinical applications. Adv Clin Chem 2015;69:1-46.  Back to cited text no. 1
    
2.
Torti FM, Torti SV. Regulation of ferritin genes and protein. Blood 2002;99:3505-16.  Back to cited text no. 2
    
3.
Hintze KJ, Theil EC. DNA and mRNA elements with complementary responses to hemin, antioxidant inducers, and iron control ferritin-L expression. Proc Natl Acad Sci U S A 2005;102:15048-52.  Back to cited text no. 3
    
4.
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;395:1054-62.  Back to cited text no. 4
    
5.
Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail [Internet]. 2020;26:4705. Available from: https://doi.org/10.1016/j.cardfail.2020.04.009. [Last accessed on 2020 Jan 12].  Back to cited text no. 5
    
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Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis 2020;63:390-1.  Back to cited text no. 6
    
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Long B, Long DA, Tannenbaum L, Koyfman A. An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction. Am J Emerg Med 2020;38:998-1006.  Back to cited text no. 7
    
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Frencken JF, van Baal L, Kappen TH, Donker DW, Horn J, van der Poll T, et al. Myocardial injury in critically ill patients with community-acquired pneumonia. A cohort study. Ann Am Thorac Soc 2019;16:606-12.  Back to cited text no. 8
    
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Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811-8.  Back to cited text no. 9
    
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Zhou B, She J, Wang Y. Utility of Ferritin, Procalcitonin, and C-reactive Protein in Severe Patients with 2019 Novel Coronavirus Disease; 2020. Available at https://doi.org/10.21203/ rs.3.rs-18079/v1 [Last accessed on 2020 May 22].  Back to cited text no. 10
    
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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.  Back to cited text no. 11
    
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Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet 2014;383:1503-16.  Back to cited text no. 12
    
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Ruscitti P, Berardicurti O, Di Benedetto P, Cipriani P, Iagnocco A, Shoenfeld Y, et al. Severe COVID-19, another piece in the puzzle of the hyperferritinemic syndrome. An immunomodulatory perspective to alleviate the storm. Front Immunol 2020;11:1130.  Back to cited text no. 13
    
14.
Bansal A, Singh AD, Jain V, Aggarwal M, Gupta S, Padappayil RP, et al. The association of D-dimers with mortality, intensive care unit admission or acute respiratory distress syndrome in patients hospitalized with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Heart Lung. 2021;50:9-12. doi: 10.1016/j.hrtlng.2020.08.024. Epub 2020 Sep 18. PMID: 33041057; PMCID: PMC7500895.  Back to cited text no. 14
    
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Patel A, Bhatt P, Madan S, Shah N, Thakkar V, Shah B, et al. A Comparative COVID 19 Characterizations and Clinical Course Analysis between ICU and Non ICU Settings. medRxiv [Internet]. 2020 Jan 1;2020.10.07.20208389. Available from: http://medrxiv.org/content/early/2020/10/11/2020.10.07.20208389.abstract [Last accessed on 2020 Jan 12].  Back to cited text no. 15
    
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Vidali S, Morosetti D, Cossu E, Luisi ML, Pancani S, Semeraro V, et al. D-dimer as an indicator of prognosis in SARS-CoV-2 infection: A systematic review. ERJ Open Res 2020;6:00260-2020.  Back to cited text no. 16
    
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Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094-9.  Back to cited text no. 17
    
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Li XY, Du B, Wang YS, Kang HY, Wang F, Sun B, et al. The keypoints in treatment of the critical coronavirus disease 2019 patient (2). Zhonghua Jie He He Hu Xi Za Zhi 2020;43:277-81.  Back to cited text no. 18
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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