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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 3  |  Page : 282-286

Procalcitonin levels in COVID-19 patients in a tertiary care center


Department of General Medicine, ESIC-PGIMSR Model Hospital, Bengaluru, Karnataka, India

Date of Submission16-Jan-2022
Date of Acceptance25-Apr-2022
Date of Web Publication17-Sep-2022

Correspondence Address:
Dr. Vaibhav S Bellary
Plot No 207, Sector 51, Saptagiri, Buda, Laxmitek, Belgaum - 590 001, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_81_22

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  Abstract 


BACKGROUND: Procalcitonin (PCT) is a glycoprotein calcitonin prohormone released by the thyroid parafollicular cells. In case of a microbial infection, PCT synthesis can be stimulated by the elevation of proinflammatory cytokines, including interleukin-6, interleukin-1b, and tumor necrosis factor-α. These mediators are massively involved in the so-called cytokine storm, typical of the progression from the viremic to the hyperinflammatory stage of COVID-19 and characterized by the onset of respiratory symptoms and interstitial pulmonary infiltrates. Thus, PCT elevation may represent a direct consequence of the COVID-19 cytokine storm and could also be interpreted as a “viral sepsis” syndrome.
AIM: (1) To estimate serum PCT levels in patients with COVID-19 infection. (2) To access PCT level as a predictor of mortality.
MATERIALS AND METHODS: A cross-sectional study was conducted on a total of 200 patients in Bengaluru during the study period from March 2021 to July 2021. A case record form with follow-up chart was used to record the duration of disease, history of treatment, and complications. Patients underwent biochemical investigations and PCT level.
RESULTS: The study includes 200 patients; the majority were above 50 years of age group. Out of 200 patients, 170 were discharged and 30 died. The mean PCT level was 4.44 ± 45.34 ng/ml. PCT in those who are discharged was 1.25 ± 8.81 ng/ml and compared to those who died was 28.06 ± 128.4 ng/ml. This difference was statistically significant (P = 0.00).
CONCLUSION: PCT can be used as a prognostic biomarker in COVID-19 patients; initially elevated levels may be used as a prognostic indicator of severity, deteriorating clinical picture, and even mortality.

Keywords: COVID-19, interleukin 6, procalcitonin, severity


How to cite this article:
Rajanna AH, Narayanashetty S, Naik YN, Bellary VS, Chethan N. Procalcitonin levels in COVID-19 patients in a tertiary care center. Indian J Health Sci Biomed Res 2022;15:282-6

How to cite this URL:
Rajanna AH, Narayanashetty S, Naik YN, Bellary VS, Chethan N. Procalcitonin levels in COVID-19 patients in a tertiary care center. Indian J Health Sci Biomed Res [serial online] 2022 [cited 2022 Sep 25];15:282-6. Available from: https://www.ijournalhs.org/text.asp?2022/15/3/282/356259




  Introduction Top


The novel coronavirus is rapidly spreading from its origin in Wuhan City of Hubei Province of China to the rest of the world.[1] Coronaviruses are enveloped positive-sense RNA viruses with spike-like projections on its surface giving it a crown-like appearance under the electron microscope.[2] Procalcitonin (PCT) is a glycoprotein calcitonin prohormone released by the thyroid parafollicular cells. In case of a microbial infection, PCT levels are significantly raised as it is released by all parenchymal tissues under the influence of endotoxins and proinflammatory cytokines.[3] Thus, in physiological state, serum PCT is recorded significantly below 0.05 ng/Ml. PCT has been used to distinguish between influenza with and without secondary bacterial infection[4] and is of potential value in identifying COVID-19 patients with genuine bacterial infection. Previous studies have investigated the role of PCT in COVID-19 infection. Williams et al.[5] described a retrospective analysis of PCT use in COVID-19 patients, concluding that PCT led to a reduction in antibiotic use without impacting on 28-day outcomes.

Severe acute respiratory syndrome (SARS)-CoV-2 is a positive-stranded RNA virus that is enclosed by a protein-decorated lipid bilayer containing a single-stranded RNA genome; SARS-CoV-2 has 82% homology with human SARS-CoV, which causes SARS.[6] The main entry receptor for SARS-CoV-2 is angiotensin-converting enzyme 2,[7] which is highly expressed in the lung alveolar cells, cardiac myocytes, vascular endothelium, and various other cell types.[8] In humans, the main route of SARS-CoV-2 transmission is through virus-bearing respiratory droplets.[9] Similar to SARS-CoV and the related Middle Eastern respiratory syndrome-CoV, SARS-CoV-2 infection induces mild symptoms in the initial stage for 2 weeks on average but has the potential to develop into severe illness, including a systemic inflammatory response syndrome, acute respiratory distress syndrome, multiorgan involvement, and shock.[10]

PCT, the precursor of the hormone calcitonin, has been used as a biomarker to aid in the diagnosis of bacterial infection or sepsis, and also in differentiating bacterial pneumonia from viral pneumonia and chronic obstructive pulmonary disease.[11],[12],[13] Diagnosis of sepsis is especially challenging as the clinical criteria for its diagnosis overlap with noninfective causes of systemic inflammation. Early diagnosis allows for timely therapeutic measures to be initiated.[14] The emergence of antibiotic resistance, on the other hand, calls for a more stringent effort to reduce antibiotic overuse. This is especially true for acute respiratory tract infections where antibiotics are prescribed often despite the majority of infections being caused by viruses rather than bacteria.[15],[16] There is growing evidence for the use of PCT-guided antibiotic therapy, both for initiation and for discontinuation of antibiotics.

Severe COVID-19 infections are characterized by a systemic inflammatory response and frequently present with pyrexia, raised C-reactive protein (CRP), hypoxia, and lung infiltrates. Clinicians have struggled to determine which COVID-19 patients have superadded bacterial infection requiring antibiotic treatment, leading to widespread antibiotic use.[17] Microbiological culture is a relatively insensitive technique, especially during antibiotic treatment. It can be difficult to distinguish infection and colonization in nonsterile sites, and even in patients with sepsis, only 30%–50% will have a positive blood culture.[18] We cannot, therefore, rely on positive microbiology alone as an indicator of bacterial infection. PCT is an inflammatory biomarker that rises in bacterial infection and falls in response to antibiotic treatment. PCT has been used to distinguish between influenza with and without secondary bacterial infection[4] and is of potential value in identifying COVID-19 patients with genuine bacterial infection. Previous studies have investigated the role of PCT in COVID-19 infection. van Berkel et al.[19] measured PCT and CRP in intensive care unit (ICU) patients with COVID-19, diagnosed with secondary bacterial infection based on a positive culture and the opinion of two ICU physicians. They concluded that low PCT could be used to exclude secondary bacterial infection. PCT has been identified as a marker of poor prognosis in COVID-19 infection.[20] It is unclear if a raised PCT is part of the inflammatory syndrome associated with COVID-19 or primarily reflects bacterial coinfection requiring antibiotic treatment.[21] However, PCT synthesis can also be stimulated by the elevation of proinflammatory cytokines, including interleukin-6 (IL)-6, IL-1b, and tumor necrosis factor-α (TNF-α).[22] These mediators are massively involved in the so-called cytokine storm, typical of the progression from the viremic to the hyperinflammatory stage of COVID-19 and characterized by the onset of respiratory symptoms and interstitial pulmonary infiltrates on chest radiology. Thus, PCT elevation may represent a direct consequence of the COVID-19 cytokine storm and could also be interpreted in the framework of a “viral sepsis” syndrome.[23]

Aims and objectives

  1. To estimate serum PCT levels in patients with COVID-19
  2. To access PCT level as a predictor of mortality.



  Materials and Methods Top


A study was conducted on a total of 200 patients in Bengaluru during the study period from March 2021 to July 2021. The data were collected from a total of 200 patients presenting to the Department of General Medicine Triage and COVID ward/ICU fulfilling the inclusion criteria.

After obtaining approval and clearance from the institutional ethics committee (532/L/11/12/Ethics/ESICMC and PGIMSR/Estt. Vol. IV), the patients fulfilling the inclusion criteria were enrolled for the study after obtaining informed consent. A case record form with follow-up chart was used to record the duration of disease, history of treatment, and complications. COVID-19 infection was diagnosed by either reverse transcription–polymerase chain reaction (RT-PCR) or rapid antigen test (RAT) technique. Patients underwent biochemical investigations, which included complete blood count, liver function test, renal function test, serum electrolytes, serology, CRP, lactate dehydrogenase, D-dimer serum ferritin, and PCT level.

Inclusion criteria:

  1. Patients willing to give written informed consent
  2. Adult patients (18 years and above) with either RT-PCR or RAT positive for COVID-19.


Exclusion criteria:

  1. Patient not willing to give informed consent
  2. Age <18 years.


Ethical clearance

Approval and clearance was obtained from the Institutional Ethics Committee (532/L/11/12/Ethics/ ESICMC and PGIMSR/Estt. Vol. IV) dated 02.12.2020.

Method of statistical analysis

The data were entered into Microsoft Excel data sheet. Categorical data were represented in the form of frequencies and proportions. Continuous data were represented as mean and standard deviation. Chi-square and Fisher's exact were used for categorical variable and t-test was used for continuous variable.


  Results Top


Demographic data

The study included 200 patients, with 9.05% of patients in the 18–30 years' age group, 34.0% were in the 30–50 years' age group, and 57% were in the above 50 years' age group. Among the recruited subjects, 117 (58.5%) were male and 83 (41.5%) of them were female [Table 1] and [Table 2].
Table 1: Descriptive statistics

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Table 2: Demographic data

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In our study, the majority of patients are diabetic (79), hypertensive (79), and cardiac disorders (17) as shown in [Table 3].
Table 3: Data on Comorbidities

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In our study subjects, out of 200 patients, 170 were discharged and 30 died. The mean PCT level was 4.44 ± 45.34 ng/ml [Table 4].
Table 4: Laboratory parameters

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In the above [Table 5], PCT in patients who were discharged was 1.25 ± 8.81 ng/ml and compared to those who died was 28.06 ± 128.4 ng/ml. This difference was statistically significant with a P value of 0.00 [Table 5].
Table 5: Parameters

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  Discussion Top


We carried out a study on 200 lab-confirmed COVID-19 patients in ESICMC and PGIMSR, Rajajinagar, Bengaluru. Out of 200 patients, 9% are in the age group of 18–30 years, 34% are in the age group of 35–50 years, and 57% are more than 50 years of age. Of the study group, 110 patients were discharged and 30 were declared dead. Our study revealed that patients with high PCT levels had worse outcome compared to patients with low PCT levels.

With the COVID-19 pandemic when no data available regarding the management, the role of laboratory evaluation and early prediction of the severity of a patients' condition was markedly highlighted.

In the absence of infection, the transcription of the Calc-I gene is suppressed, and the calcitonin peptide families circulate as free peptides at low concentrations in the serum of healthy individuals. When systemic bacterial infection occurs, the tissue-specific control of Calc-I is disrupted, and the expression of Calc-I gene is increased, leading to the massive release of PCT.

Research has shown that the synthesis and secretion of PCT may be induced either directly via endotoxins as well as lipopolysaccharides or indirectly via proinflammatory cytokines, such as TNF α and IL-6. PCT is formed by transcription and translation in C cells near thyroid follicles using Calc-I as the template. Under normal conditions, PCT is quickly cleaved into three parts: N-terminal fragment, peptides calcitonin, and katacalcin.[24] SARS-CoV-2 can trigger an inflammatory cascade via the release of proinflammatory cytokines, such as IL-1 and IL-6, after activating toll-like receptors which are also known to stimulate the release of PCT.[25] Patients with severe COVID 19 can develop immune hyperactivation and cytokine storm accompanied with a high level of PCT. It has been shown that a reasonable explanation for elevated PCT in severe COVID 19 patients is coinfection with bacteria.[26]

In our study, PCT in patients who were discharged was 1.25 ± 8.81 and compared to those who died was 28.06 ± 128.4. This difference was statistically significant with a P value of 0.00 [Table 5]. To further substantiate this association, our results revealed 51 studies reported either a significant association between PCT and severity or markedly elevated PCT levels in the severe patients group, making it a reliable prognostic biomarker. However, Li et al. reported no significant association between PCT and prognosis in COVID-19 cases, which could be due to a small proportion of critically ill (n = 5) and expired (n = 11) cases and the findings could vary if a larger cohort is evaluated.[27] As the PCT release is thought to be inhibited by interferon-γ upsurge, it is expected that the PCT value would remain significantly lower than the optimal cutoff in cases with noncritical or severe infection.[28]

Limitations

  1. Sample size was a small and single-center study.



  Conclusion Top


PCT can be used as a prognostic biomarker in COVID-19 patients; initially elevated PCT levels may be used as a prognostic indicator of severity, deteriorating clinical picture, and even mortality in COVID-19.

Financial support and sponsorship

Nil.

Conflicts of interest



 
  References Top

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Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020;395:470-3.  Back to cited text no. 1
    
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Ahmed S, Siddiqui I, Jafri L, Hashmi M, Khan AH, Ghani F. Prospective evaluation of serum procalcitonin in critically ill patients with suspected sepsis- experience from a tertiary care hospital in Pakistan. Ann Med Surg (Lond) 2018;35:180-4.  Back to cited text no. 3
    
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Huang DT, Yealy DM, Filbin MR, Brown AM, Chang CH, Doi Y, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med 2018;379:236-49.  Back to cited text no. 4
    
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Williams EJ, Mair L, de Silva TI, Green DJ, House P, Cawthron K, et al. Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: A retrospective cohort study. J Hosp Infect 2021;110:103-7.  Back to cited text no. 5
    
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Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281-92.e6.  Back to cited text no. 7
    
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Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586-90.  Back to cited text no. 8
    
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Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 9
    
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Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) Outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.  Back to cited text no. 10
    
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Meynaar IA, Droog W, Batstra M, Vreede R, Herbrink P. In critically ill patients, serum procalcitonin is more useful in differentiating between sepsis and SIRS than CRP, IL6, or LBP. Crit Care Res Pract 2011;2011:594645.  Back to cited text no. 11
    
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Briel M, Schuetz P, Mueller B, Young J, Schild U, Nusbaumer C, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med 2008;168:2000-7.  Back to cited text no. 12
    
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Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96.  Back to cited text no. 13
    
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Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114-21.  Back to cited text no. 15
    
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Seaton RA, Gibbons CL, Cooper L, Malcolm W, McKinney R, Dundas S, et al. Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals. J Infect 2020;81:952-60.  Back to cited text no. 16
    
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Murray PR, Masur H. Current approaches to the diagnosis of bacterial and fungal bloodstream infections in the intensive care unit. Crit Care Med 2012;40:3277-82.  Back to cited text no. 17
    
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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. 19
    
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Vanhomwegen C, Veliziotis I, Malinverni S, Konopnicki D, Dechamps P, Claus M, et al. Procalcitonin accurately predicts mortality but not bacterial infection in COVID-19 patients admitted to intensive care unit. Ir J Med Sci 2021;190:1649-52.  Back to cited text no. 20
    
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Russwurm S, Wiederhold M, Oberhoffer M, Stonans I, Zipfel PF, Reinhart K. Molecular aspects and natural source of procalcitonin. Clin Chem Lab Med 1999;37:789-97.  Back to cited text no. 21
    
22.
Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci 2020;57:389-99.  Back to cited text no. 22
    
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Li H, Liu L, Zhang D, Xu J, Dai H, Tang N, et al. SARS-CoV-2 and viral sepsis: Observations and hypotheses. Lancet 2020;395:1517-20.  Back to cited text no. 23
    
24.
Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies. J Biol Regul Homeost Agents 2020;34:327-31.  Back to cited text no. 24
    
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Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.  Back to cited text no. 25
    
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Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 26
    
27.
Li H, Xiang X, Ren H, Xu L, Zhao L, Chen X, et al. Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis. J Infect 2020;80:646-55.  Back to cited text no. 27
    
28.
Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci 2020;57:389-99.  Back to cited text no. 28
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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