• Users Online: 110
  • Print this page
  • Email this page

 
Table of Contents
CORRESPONDENCE
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
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_70_20

Rights and Permissions

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

Click here to view


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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
    
2.
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
    
3.
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
    
4.
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
    
5.
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
  [Full text]  
6.
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
    
7.
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
    
8.
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
    


    Figures

  [Figure 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
References
Article Figures

 Article Access Statistics
    Viewed38    
    Printed2    
    Emailed0    
    PDF Downloaded8    
    Comments [Add]    

Recommend this journal