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Table of Contents
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 249-250

Authors' response

Department of Medicine, All India Institute of Medical Sciences, New Delhi, India

Date of Submission18-Aug-2020
Date of Acceptance04-Sep-2020
Date of Web Publication5-Jan-2021

Correspondence Address:
N Wig
Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JCSR.JCSR_70_20

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How to cite this article:
Praveen T, Desai D, Soneja M, Wig N. Authors' response. J Clin Sci Res 2020;9:249-50

How to cite this URL:
Praveen T, Desai D, Soneja M, Wig N. Authors' response. J Clin Sci Res [serial online] 2020 [cited 2021 Jan 20];9:249-50. Available from: https://www.jcsr.co.in/text.asp?2020/9/4/249/306196

We thank Rao and Nagesh[1] for their interest in contributing to the understanding of immunodysregulation in coronavirus disease 2019 (COVID-19) pneumonia and highlighting the importance of renin–angiotensin system (RAS) pathway and interleukin-6 (IL-6) in driving cytokine storm. The authors reasoned that the crux of the pathogenesis lies in the dysregulated RAS axis which subsequently drives cytokine storm and also downregulates CD8+/natural killer (NK) cell activity. We agree with the authors that RAS pathway is very important in driving inflammation and NK cell dysfunction could be secondary to high IL-6 levels in patients with severe disease. However, the high IL-6 levels are seen more in the later part of the course of the disease, whereas lymphopenia, decreased NK cell number and function have also been demonstrated even in mild cases.[2],[3] We postulate that the underlying immune defects (lymphopenia and NK cell dysfunction) in particular populations (elderly, malignancy and obesity) lead to ineffective clearance of the virus and a subsequent higher possibility of severe disease[4] [Figure 1]. In our review, we did mention about the biphasic nature of the immune response where immunoparalysis sets in after a phase of hyperinflammation.[5]
Figure 1: The vicious cycle of immune defects leading to reduced viral clearance and severe COVID-19 which further induces immune defects. NK = Natural killer; COVID-19 = severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease

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The authors suggest that the immune response in severe COVID-19 may be particularly distinct from other aetiologies driving high IL-6. However, we believe that increase in IL-6 levels is not specific for COVID-19 and very high levels of IL-6 (more than what is seen in severe COVID-19) have been previously demonstrated in sepsis and other causes of ARDS.[6],[7],[8] We acknowledge the gaps in our understanding of the COVID-19 immune response and the need for further research in the same area.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Rao SN, Nagesh S. Renin-angiotensin axis as a trigger for immune dysregulation in COVID-19. J Clin Sci Res XX; XX: XX.  Back to cited text no. 1
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020;17:533-5.  Back to cited text no. 2
Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, et al. Lymphopenia predicts disease severity of COVID-19: A descriptive and predictive study. Signal Transduct Target Ther 2020;5:1-3.  Back to cited text no. 3
Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R, et al. Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Ann Oncol 2020;31:894-901.  Back to cited text no. 4
Praveen T, Desai D, Soneja M, Wig N. Immune dysregulation in COVID-19 and its therapeutic implications. J Clin Sci Res 2020;9:37.  Back to cited text no. 5
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Hou T, Huang D, Zeng R, Ye Z, Zhang Y. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: A systematic review and meta-analysis. Int J Clin Exp Med 2015;8:15238-45.  Back to cited text no. 6
Song J, Park DW, Moon S, Cho HJ, Park JH, Seok H, et al. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect Dis 2019;19:968.  Back to cited text no. 7
Hui L, Zhang X, An X, Li J, Zang K, Shang F, et al. Higher serum procalcitonin and IL-6 levels predict worse diagnosis for acute respiratory distress syndrome patients with multiple organ dysfunction. Int J Clin Exp Pathol 2017;10:7401-7.  Back to cited text no. 8


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