|Year : 2020 | Volume
| Issue : 4 | Page : 249-250
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|
Professor and Head, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 029
Source of Support: None, Conflict of Interest: None
|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 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., 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 [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.
|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.,, 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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rao SN, Nagesh S. Renin-angiotensin axis as a trigger for immune dysregulation in COVID-19. J Clin Sci Res XX; XX: XX.
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.
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.
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.
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]
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.
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.
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.