Introduction
The COVID-19 or the Coronavirus pandemic took far more severe a turn than one could have imagined. The severe acute respiratory syndrome caused by Coronavirus spread quickly and confirmed the death of many people worldwide. Several definite diagnostic parameters were determined to deal with this viral infection. Pathological tests that were found relevant to diagnose COVID-19 infection included RT PCR (Real-Time Polymerase Chain Reaction), D-Dimer, chest X-ray, CRP (C-Reactive Protein), and HRCT (High-Resolution Computed Tomography).
However, few studies have shown a correlation between the severity of Covid-19 infection and increased levels of PCT or Procalcitonin in the blood. How? Keep reading.
What is procalcitonin?
Procalcitonin is a precursor of the hormone called calcitonin, a calcium regulating hormone. It consists of 116 amino acids and is mainly produced by the thyroid cells. In a healthy individual, the procalcitonin levels in the blood are minimal as a maximum of it gets used to synthesize calcitonin. The produced calcitonin is then stored in the body reserves and used in a definite manner to conduct various functions of the body, such as calcium homeostasis.
Procalcitonin as a diagnostic marker
The sole function of procalcitonin is to generate calcitonin, of which only a minimal amount enters the bloodstream. High procalcitonin levels suggest a systemic inflammatory condition, mainly bacterial infection. It occurs due to the activation of an alternative pathway. This activation encourages more procalcitonin to flow in the blood instead of contributing to the synthesis of calcitonin.
This feature of procalcitonin was relevant in making the diagnosis stronger for a bacterial infection and assisting in the therapeutic ventures. Furthermore, procalcitonin levels are known to rise rapidly when an infection is at its peak and then fall when the infection is resolved. This helps in deciding the antibiotic therapy, its doses, and the required alterations in the course of the treatment.
The known limitation to procalcitonin was that it helps diagnose an inflammatory response of the body only when its origin is a bacterial species. Therefore, no viral infection was found to seek the support of procalcitonin for its detection until the emergence of the coronavirus pandemic.
Moreover, the levels of procalcitonin were also seen on the higher side in conditions such as burns, trauma, after intestinal surgery, heart attack, pancreatitis, and certain carcinomas.
Contribution of Procalcitonin to COVID-19
Increased levels of procalcitonin have been associated with coronavirus infection diagnosis, although it has been recognized as a reliable biomarker in the case of bacterial infection.
Referring to the previous studies, most of the time, it is concluded that the synthesis and the following release of procalcitonin in the bloodstream are regulated or intensified in the presence of bacterial infection. The reason behind this enhanced extra-thyroid release of procalcitonin is the activation of the various metabolites such as TNF-α(Tumor Necrosis Factor), IL-6 (Interleukin), and bacterial endotoxins. The metabolite interferon (INF)-γ is known for suppressing the production of this biomarker, i.e., procalcitonin. Also, (INF)-γ is the one whose levels are elevated during the viral infection.
If analyzed in all ways, there would be no change in procalcitonin levels when the body is under coronavirus infection. So it will not be considered an overstatement if we regard procalcitonin as a biomarker for diagnosing bacterial infections, not viral infections.
However, as per the article from the Advances in Motion, Massachusetts General Hospital, a few studies conducted in China showed elevated levels of procalcitonin in almost about 30% of patients suffering from COVID-19.
A few likelihoods suggest the rise of procalcitonin level during COVID-19 infection. They are given as follows:
- Bacterial co-infection
The severity of the covid infection is marked by pneumonia in most cases. At times, viral pneumonia gets converted into bacterial, which is not evident. The reason is that the symptoms of bacterial pneumonia could be confused with the moderate level of covid-19 infection. Also, it has been recorded that patients with severe COVID-19 infection (hospitalized in ICU) had a high rate of bacterial co-infection.
Though procalcitonin is a poor diagnostic marker for covid, it could help determine any inflammatory syndrome that is not specifically covid but has a close association with it, such as bacterial co-infection. Levels of procalcitonin were significantly dropped when covid infected patients were offered antibiotic therapy. An antibiotic treatment would not work on a viral infection such as covid; however, it could essentially take charge of curing the underlying bacterial infection. This indirect analysis suggests the possibility of an underlying bacterial co-infection in the covid patients, which elevates the procalcitonin levels in the blood.
- Immune dysregulation
Coronavirus causes an infection that essentially targets the lungs leading to severe respiratory disorders. At an advanced stage, the infection could even result in respiratory failure. This condition initiates the increased production of cytokines that stand as metabolites for commencing the alternative pathway for procalcitonin synthesis. The standard pathway is impeded, hindering calcitonin production, doubling the procalcitonin levels into the bloodstream. Thus, immune dysregulation due to the severity of covid infection could stand as one of the possibilities for high procalcitonin levels.
- Respiratory problem
COVID-19 could result in manifestations of a spectrum of respiratory problems. Acute Respiratory Distress Syndrome (ARDS) is quite a severe respiratory complication that needs to be treated on time, or else it could take a fatal turn. ARDS is a life-threatening medical condition marked by the leakage of fluid in the lungs. The accumulation of this fluid makes it difficult for an individual to breathe; as a result, the oxygen level of the body drops.
It was found that many patients with severe ARDS showed increased levels of serum procalcitonin due to an injury to the lung, which triggers its synthesis. In addition, the severity of ARDS could be correlated with elevated procalcitonin levels, making it appear as an excellent prognostic marker to some extent.
The ambiguous note
Many patients with severe COVID-19 infection featured high levels of procalcitonin. However, the degree of severity varied in each study intended to find the usefulness of procalcitonin as a diagnostic parameter for Coronavirus. Thus, it becomes difficult to interpret due to the unclear available data. However, it could be inferred that most studies emphasized the possibility of co-infection caused by bacterial species.
Note: It is vital to correlate the procalcitonin levels with other clinical findings as it is insufficient to suggest a particular medical condition independently.
References:
- Hu R, Han C, Pei S, Yin M, Chen X. Procalcitonin levels in COVID-19 patients. Int J Antimicrob Agents [Internet]. 2020;56(2):106051. Available from: http://dx.doi.org/10.1016/j.ijantimicag.2020.106051
- Radiology management, ICU management, healthcare IT, cardiology management, executive management. 2022 [cited 2022 Feb 6]; Available from: https://healthmanagement.org/c/healthmanagement/issuearticle/the-role-of-procalcitonin-for-risk-assessment-and-treatment-of-covid-19-patients
- Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta [Internet]. 2020;505:190–1. Available from: http://dx.doi.org/10.1016/j.cca.2020.03.004
- Meaning of elevated procalcitonin unclear in COVID-19 [Internet]. Mass General Advances in Motion. 2020 [cited 2022 Feb 6]. Available from: https://advances.massgeneral.org/research-and-innovation/article.aspx?id=1174
- Williams P, McWilliams C, Soomro K, Harding I, Gurney S, Thomas M, et al. The dynamics of procalcitonin in COVID-19 patients admitted to Intensive care unit – a multi-centre cohort study in the South West of England, UK. J Infect [Internet]. 2021 [cited 2022 Feb 6];82(6):e24–6. Available from: https://www.journalofinfection.com/article/S0163-4453(21)00128-6/fulltext
- Rowland T, Hilliard H, Barlow G. Procalcitonin: potential role in diagnosis and management of sepsis. Adv Clin Chem [Internet]. 2015 [cited 2022 Feb 6];68:71–86. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/procalcitonin
- Yu Z, Ji M, Hu X, Yan J, Jin Z. Value of procalcitonin on predicting the severity and prognosis in patients with early ARDS: a prospective observation study. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue [Internet]. 2017;29(1):34–8. Available from: http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.01.008
