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| CORRESPONDENCE |
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| Year : 2020 | Volume
: 9
| Issue : 4 | Page : 249-250 |
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Authors' response
T Praveen, D Desai, M Soneja, N Wig
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
| Date of Submission | 18-Aug-2020 |
| Date of Acceptance | 04-Sep-2020 |
| Date of Web Publication | 5-Jan-2021 |
Correspondence Address:
N Wig
Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 029
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JCSR.JCSR_70_20
How to cite this article:
Praveen T, Desai D, Soneja M, Wig N. Authors' response. J Clin Sci Res 2020;9:249-50 |
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Rao SN, Nagesh S. Renin-angiotensin axis as a trigger for immune dysregulation in COVID-19. J Clin Sci Res XX; XX: XX.  |
| 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. |
| 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. |
| 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. |
| 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. [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. |
| 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. |
| 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. |
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