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Deciphering new turns of cytokine storm in COVID-19

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Since the cytokine storm appears to be one of the common causes of mortality in the COVID-19 pandemic, Dr Yatin Mehta, chairman, Medanta Institute of Critical Care and Anesthesiology, Medanta the Medicity, Gurgaon posits that the early recognition of cytokine storm and the prompt treatment may lead to better outcome

Ever since the outbreak of COVID-19, the term ‘cytokine storm’ has become increasingly used across different spectrums. The widespread use of this term is likely related to its rather immediate meaning, which recalls the role of the immune system in producing an uncontrolled and generalised inflammatory response [1].

The COVID-19 infection is accompanied by an aggressive inflammatory response with the release of a large amount of pro-inflammatory cytokines in an event known as ‘cytokine storm’. The host immune response to the SARS-CoV-2 virus is hyperactive resulting in an excessive inflammatory reaction. Several studies analysing cytokine profiles from COVID-19 patients suggested that the cytokine storm correlated directly with lung injury, multi-organ failure, and unfavourable prognosis of severe COVID-19 infection [2].

Cytokine atorm also plays an important role in the process of disease aggravation [3]. Clinical studies have detected a cytokine storm in critical patients with COVID-19. Therefore, effectively suppressing the cytokine storm is an important way to prevent the deterioration of patients with COVID-19 infection and save their lives [4].

Also, abnormal and uncontrolled production of cytokines has been observed in critically ill patients with COVID-19 pneumonia. And the ensuing uncontrolled cytokine storm in COVID-19 patients is centrally involved in the exacerbation of symptoms and disease development and represents a major factor contributing to COVID-19 mortality. In this sense, COVID-19 disease shares similarities with other viral diseases such as SARS, MERS and influenza, where the development of a cytokine storm is a warning sign of disease escalation [5].

In tandem with the above observations, a retrospective study of 41 patients with COVID-19 showed that most SARS-CoV-2 infected patients present clinically with mild symptoms, while a minority of patients progressively declining due to the infection and eventually dying of Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MOD). Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia was first published on January 30, 2020, and recommended for the first time that cytokine monitoring be applied to improve the curative rate and reduce mortality [6].

The health care providers have observed that cytokine storm suffered in COVID-19 is causing major complications and death. Cytokines are supposed to destroy novel coronavirus, but the levels go so high, that they are destroying organs wherein most of the patients who are critically ill due to the failure of their kidneys, need urgent kidney replacement therapy or dialysis [7].

In case of kidney failure due to ‘cytokine storm’ wherein urgent dialysis is required, the continuous renal replacement therapy (CRRT) may be one of the preferred modalities, especially for those who have hemodynamic instability, as recommended by American Society of Nephrology in the case of COVID-19 pandemic.

CRRT is a blood purification therapy applied for 24 hours a day. At present, among the other therapies being used, CRRT is beneficial in maintaining volume balance, haemodynamic stability and to improve the clearance efficiency of middle-sized molecules such as cytokines especially when used with adsorptive filters which can help with the improved clearance of cytokines from circulation [8].

Besides benefiting severely ill patients by removing potentially harmful components and maintaining haemodynamic and metabolic status, CRRT can be used to regulate the immune response of patients with sepsis, with the goal to regulate circulating levels of inflammatory cytokine mediators [9].

The COVID-19 conundrum has put an unprecedented burden over the entire healthcare ecosystem wherein the role of healthcare workers whether it is a specialist or an assistant has become utmost crucial. In the team of COVID-19 doctors, the essence of intensive care specialists has increased significantly given the condition that the cytokines are affecting organs like the heart and kidneys. Also as per the observational studies, 25-30 per cent critically ill patients of COVID-19 suffer with Acute Kidney Injury (AKI).

Cytokine storm appears to be one of the common causes of mortality in the COVID-19 pandemic, hence the early recognition of cytokine storm and the prompt treatment may lead to better outcome. [10]

 References:

  1. https://www.sciencedirect.com/science/article/pii/S1359610120300927#:~:text=COVID%2D19%20pandemic%20is%20raging,care%20systems%20under%20severe%20strain.&text=The%20%E2%80%9Ccytokine%20storm%E2%80%9D%20and%20the,of%20several%20immune%2Dactive%20molecules.&text=The%20%E2%80%9Ccytokine%20storm%E2%80%9D%20is%20the,event%20related%20to%20COVID%2D19. J.R. Tisoncik, M.J. Korth, C.P. Simmons, J. Farrar, T.R. Martin, M.G. Katze, Into the eye of the cytokine storm, Microbiol. Mol. Biol. Rev., 76 (1) (2012), pp. 16-32.
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308649/
  3. Subhal Dixit, Yatin Mehta, Kapil Zirpe, Abdul Ansari. Cytokine storm in novel coronavirus disease (covid-19): expert management considerations”. Indian J Crit Care Med 2020;24(6):429–434.
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194613/ Wan S., Yi Q., Fan S., Lv J., Zhang X., Guo L., et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). 2020:medRxiv2020.02.10.20021832.
  5. https://www.sciencedirect.com/science/article/pii/S1359610120300484 J.T. Wu, K. Leung, G.M. Leung Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study Lancet (2020)
  6. https://www.sciencedirect.com/science/article/pii/S1359610120300484 Y.H. Jin, L. Cai, Z.S. Cheng, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) Mil. Med. Res., 7 (1) (2020), p. 4
  7. https://www.thailandmedical.news/news/covid-19-cytokine-storms-nephrologists-invent-new-blood-filters-for-use-in-dialysis-machines-to-remove-cytokines-in-covid-19-patients
  8. https://www.asn-online.org/ntds/resources/Webcast_2020_04_21_AKI!NOW.mp4
  9. https://www.sciencedirect.com/science/article/pii/S1359610120300484
  10. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01446/full

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