Unveiling the role of procalcitonin in COVID-19: a literature review
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20240298Keywords:
COVID-19, SARS-CoV-2, Pro-Calcitonin, PCT, BiomarkerAbstract
Procalcitonin (PCT), a key hormone regulating calcium homeostasis, has previously shown the potential to differentiate between bacterial and viral infections. However, when we move further into the field of COVID-19 pandemic, an unprecedented question was raised: Can PCT levels increase without bacterial co-infection in SARS-CoV-2 infection? This review systematically searched PubMed, Scopus, and Google Scholar for articles on procalcitonin (PCT) in the context of COVID-19 published from 2019 to 2023. Inclusion criteria focused on relevant articles, excluding non-English publications. Increasing PCT levels were observed in COVID-19 patients, especially in severe cases, often interpreted as evidence of bacterial co-infection. However, the role of PCT in the immune response to SARS-CoV-2 remains unclear. The proposed mechanisms suggest that SARS-CoV-2 can stimulate the production of PCT even in the absence of bacterial co-infection by modulating the interferon (IFN) pathway and reducing the regulation of monocyte function. Furthermore, PCT has implications in antibiotic management, with guidelines recommended to avoid antibiotics in patients with low serum PCT levels. Increased PCT values show associations with the severity of disease, including increased mortality, which further underlines the need for a detailed understanding of the dynamics of the PCT in COVID-19. This review emphasizes the evolving significance of PCT in COVID-19, with elevated PCT levels emerging as a valuable prognostic indicator, aiding in disease severity assessment and management. However, the intricate dynamics of PCT in COVID-19 demand further investigation, particularly in distinguishing viral infection from bacterial co-infection.
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References
Lugito NPH. Is procalcitonin a part of human immunological response to SARS-CoV-2 infection or "just" a marker of bacterial coinfection? Curr Res Transl Med. 2021;69(2):103289.
Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006;34(7):1996-2003.
Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008;36(3):941-52.
Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007;7(3):210-7.
Linscheid P, Seboek D, Nylen ES, Langer I, Schlatter M, Becker KL, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology. 2003;144(12):5578-84.
Anand D, Das S, Ray S, Bhargava S, Srivastava LM. Interrelationship between procalcitonin and organ failure in sepsis. Indian J Clin Biochem. 2014;29(1):93-6.
Lai CC, Wang CY, Hsueh PR. Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents? J Microbiol Immunol Infect. 2020;53(4):505-12.
Martins-Filho PR, Tavares CSS, Santos VS. Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data. Eur J Intern Med. 2020;76:97-9.
Tang ML, Li YQ, Chen X, Lin H, Jiang ZC, Gu DL, et al. Co-Infection with Common Respiratory Pathogens and SARS-CoV-2 in Patients with COVID-19 Pneumonia and Laboratory Biochemistry Findings: A Retrospective Cross-Sectional Study of 78 Patients from a Single Center in China. Med Sci Monit. 2021;27:e929783.
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(10223):497-506.
Liu ZM, Li JP, Wang SP, Chen DY, Zeng W, Chen SC, et al. Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19. Int J Med Sci. 2020;17(16):2468-76.
Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clinica Chimica Acta Int J Clin Che. 2020;505:190-1.
Matsuyama T, Kubli SP, Yoshinaga SK, Pfeffer K, Mak TW. An aberrant STAT pathway is central to COVID-19. Cell Death Differ. 2020;27(12):3209-25.
Le Y, Chen T, Xun K, Ding T. Expression of the Long Intergenic Non-Coding RNA (lincRNA) of the NED25 Gene Modulates the microRNA-125b, STAT3, Nitric Oxide, and Procalcitonin Signaling Pathways in Patients with Sepsis. Med Sci Monit. 2018;24:4555-66.
Yang D, Chu H, Hou Y, Chai Y, Shuai H, Lee AC, et a;. Attenuated Interferon and Proinflammatory Response in SARS-CoV-2-Infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation. J Infect Dis. 2020;222(5):734-45.
Martinez FO, Combes TW, Orsenigo F, Gordon S. Monocyte activation in systemic Covid-19 infection: Assay and rationale. EBioMedicine. 2020;59:102964.
Cecconi M, Piovani D, Brunetta E, Aghemo A, Greco M, Ciccarelli M, et al. Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy. J Clin Med. 2020;9(5):1548.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, etal. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13.
Nasir N, Rehman F, Omair SF. Risk factors for bacterial infections in patients with moderate to severe COVID-19: A case-control study. J Med Virol. 2021;93(7):4564-9.
May M, Chang M, Dietz D, Shoucri S, Laracy J, Sobieszczyk ME, et al. Limited Utility of Procalcitonin in Identifying Community-Associated Bacterial Infections in Patients Presenting with Coronavirus Disease 2019. Antimicrob Agents Chemother. 2021;65(4):e02167-20.
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.
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.
Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect. 2020;81(2):e16-25.
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(10229):1054-62.
Zhang JJY, Lee KS, Ang LW, Leo YS, Young BE. Risk Factors for Severe Disease and Efficacy of Treatment in Patients Infected With COVID-19: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis. Clin Infect Dis. 2020;71(16):2199-206.
Meier MA, Branche A, Neeser OL, Wirz Y, Haubitz S, Bouadma L, et al. Procalcitonin-guided Antibiotic Treatment in Patients With Positive Blood Cultures: A Patient-level Meta-analysis of Randomized Trials. Clin Infect Dis. 2019;69(3):388-96.
Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059-66.
Thaden JT, Maskarinec SA. When two for the price of one isn't a bargain: estimating prevalence and microbiology of bacterial co-infections in patients with COVID-19. Clin Microbiol Infect. 2020;26(12):1602-3.
Albrecht T, Fons M, Boldogh I. Effects on Cells. In: Baron S, eds. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.
McCullers JA. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol. 2014;12(4):252-62.
Ahmed S, Jafri L, Hoodbhoy Z, Siddiqui I. Prognostic Value of Serum Procalcitonin in COVID-19 Patients: A Systematic Review. Indian J Crit Care Med. 2021;25(1):77-84.
