Number of natural killer cells and cytokine levels in peripheral blood at various degrees of severity
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Keywords:
COVID-19, severity, NK cells, cytokines
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Abstract
This study aims to investigate NK cell number and cytokines level in various degrees of severity in COVID-19 cases. A total of 63 COVID-19 patient aged >18 y were divided into mild-moderate and severe-critical groups. Patient characteristics and peripheral blood count were obtained from medical records. NK cells number, levels of IFN-?, IL-10, and IL-12 in peripheral blood were examined by means of flow cytometry. The severe-critical group had leukocytosis, neutrophilia, lymphopenia, higher Neutrophil Lymphocyte Ratio, lower NK cell number and higher level of IL-10. In severe-critical group, those aged >60 years had higher IL-10. In both groups, patients with diabetes comorbidities had a higher number of NK cells (p<0.05). NK cell number and IL-10 in peripheral blood have potential as a predictor of severe COVID-19 patients.
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Devita, N., Arjana, A. Z., Intansari, U. S., & Susilowati, R. (2023). Number of natural killer cells and cytokine levels in peripheral blood at various degrees of severity. Communications in Science and Technology, 8(1), 66-74. https://doi.org/10.21924/cst.8.1.2023.1106
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V. Mxinwa, P.V. Dludla, T.M. Nyambuya, K. Mokgalaboni, S.E. Mazibuko-mbeje, B.B. Nkambule, Natural killer cell levels in adults living with type 2 diabetes?: a systematic review and meta-analysis of clinical studies, BMC Immunol. 21(2020) 51-70.
W. De Jager, K. Bourcier, G.T. Rijkers, B.J. Prakken, V. Seyfert-Margolis, Prerequisites for cytokine measurements in clinical trials with multiplex immunoassay, BMC Immunol. 10 (2009).
Kemenkes RI. Ikhtisar Penanganan COVID-19. Jakarta: Kemenkes RI, 2022.
P.H.. Tsai, W.Y. Lai, Y.Y. Lin, Y.H. Luo, Y.T. Lin, H.K. Chen, et al., Clinical manifestation and disease progression in COVID-19 infection, J Chinese Med Assoc. 84 (2021) 3–8.
Kemenkes RI. Pedoman Tatalaksana COVID-19: edisi 2, Indonesia: Kementrian Kesehatan RI, 2020.
D.S. Oliveira, N.I. Medeiros, J.A.S. Gomes, Immune response to COVID-19: What do we currently know?, Microb Pathog.. 148 (2020).
P. Parham. The Immune System. 4th edition. New York: Garland Science, 2015.
F. Ahmed, D.H. Jo, S.H. Lee, Can Natural Killer Cells Be a Principal Player in Anti-SARS-CoV-2 Immunity?, Front Immunol. 11 (2020) 1-8.
C. van Eeden, L. Khan, M.S. Osman, J.W.C. Tervaert, Natural killer cell dysfunction and its role in COVID-19, Int J Mol Sci. 21 (2020) 1–17.
K. Schroder, P.J. Hertzog, T. Ravasi, D.A. Huve, Interferon-?: an overview of signals, mechanisms, and functions, J Leukoc Biol. 75 (2004) 163–169.
Y. Jiang, X. Wei, J. Guan, S. Qin, Z. Wang, H. Lu, et al,. COVID-19 pneumonia: CD8+ T and NK cells are decreased in number but compensate for increases in cytotoxic potential, Clin Immunol. 218 (2020).
A. Mazzoni, L. Salvati, L. Maggi, M. Capone, A. Vanni, M. Spinicci, et al., Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent,. J Clin Invest. 130 (2020) 4694–49703.
C. Qin, L. Zhou, Z. Hu, S. Zhang, S. Yang, Y. Tao, et al., Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China, Clin Infect Dis. 71 (2020) 762–728.
M. Osman, R.M. Faridi, W. Sligl, M.T. Shabani-Rad, P. Dharmani-Khan, A. Parker, et al., Impaired natural killer cell counts and cytolytic activity in patients with severe COVID-19, Blood Adv. 4 (2020) 5035–5039.
H. Han, Q. Ma, C. Li, R. Liu, L. Zhao, W. Wang, et al., Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors, Emerg Microbes Infect. 9 (2020) 1123–1130.
M. Market, L. Angka, A.B. Martel, D. Bastin, O. Olanubi, G. Tennakoon, et al., Flattening the COVID-19 Curve With Natural Killer Cell-Based Immunotherapies,. Front Immunol. 11(2020) 1–23.
H. Islam, T.C. Chamberlain, A.L. Mui, J.P Little, Elevated Interleukin-10 Levels in COVID-19: Potentiation of Pro-Inflammatory Responses or Impaired Anti-Inflammatory Action?, Front Immunol. 12 (2021) 10–14.
N. Mangalmurti, C.A. Hunter, Cytokine Storms: Understanding COVID-19, Immunity. 53 (2020) 19–25.
R. Moll-Bernardes, A.S. de Sousa, A.V.S. Macedo, R.D. Lopes, N. Vera, L.C.R. Maia, et al., IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Tria, Front Cardiovasc Med. 8 (2021) 1–10.
L.H. Tjan, K. Furukawa, T. Nagano, T. Kiriu, M. Nishimura, J. Arii, et al., Early Differences in Cytokine Production by Severity of Coronavirus Disease 2019, J Infect Dis. 223 (2021) 1145–1149.
J. Jin, P. Bai, F. Wu, X. Liu, D. Han, S. Liu, J. Yang, Gender Differences in Patients With COVID-19:Focus on Severity and Mortality, Front. Public Health. 152 (2020).
T.A. Khartabil, H. Russcher, A. van der Ven, Y.B. de Rijke, A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients, Crit Rev Clin Lab Sci. 57 (2020) 415–431.
W. Guan, Z. Ni, Y. Hu, W. Liang, C. Ou, J. He, et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med. 328 (2020) 1708–1720.
K. Zhao, R. Li, X. Wu, Y. Zhao, T. Wang, Z. Zheng, et al., Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis, Eur J Clin Microbiol Infect Dis. 39 (2020) 2279–2287.
A.P. Yang, J. Liu, W. Tao, H. Lee, The diagnostic and predictive role of NLR, d-NLR, and PLR in COVID-19 patients, Bioorg Chem. 103 (2020).
K.U. Toori, M.A. Qureshi, A. Chaudhry, M.F. Safdar, Neutrophil to lymphocyte ratio (NLR) in COVID-19: A cheap prognostic marker in a resource constraint setting, Pak J Med Sci. 37 (2021) 1435-1439.
F. Andiani F, R. Herawati, Y. Triyani, Correlation between NLR and PLR with the Severity of COVID-19 Inpatients, Indonesian J. Clin. Pathol. Med. Lab. 29 (2022) 37-53.
H.G. Munshi, R.B. Montgomery, Severe neutropenia: a diagnostic approach, West J Med. 172 (2000) 248-52.
E. McKenna, R. Wubben, J.M. Isaza-Correa, A.M. Melo, A.U. Mhaonaigh, N. Conlon N, et al., Neutrophils in COVID-19: Not Innocent Bystanders, Front Immunol. 13 (2022) 1–12.
F. Wang, H. Hou, Y. Luo, G. Tang, S. Wu, M. Huang, et al., The laboratory tests and host immunity of COVID-19 patients with different severity of illness, JCI Insight. 5 (2020) 1–11.
M.L. Meizlish, A.B. Pine, J.D. Bishai, G. Joshua, E.R. Nadelmann, M. Simonov, et al., A neutrophil activation signature predicts critical illness and mortality in COVID-19, Blood Adv. 5 (2021) 1164–1177.
M. Ackermann, H.J. Anders, R. Bilyy, G.L. Bowlin, C. Daniel, R. De Lorenzo, et al., Patients with COVID-19: in the dark-NETs of neutrophils, Cell Death Differ. 28 (2021) 3125–3139.
F. Wang, J. Nie, H. Wang, Q. Zhao, Y. Xiong, L. Deng, et al., Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia, J Infect Dis. 221 (2020) 1762–1769.
L. Yang, X. Xie, Z. Tu, J. Fu, D. Xu, Y. Zhou, The signal pathways and treatment of cytokine storm in COVID-19, Signal Transduct Target Ther. 6 (2021) 1–20.
C. Quan, C. LI, H. Ma, Y. Li, H. Zhang, Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection_Associated Hemophagocytic Lymphohistiocytosis, 34, Clin Microbiol Rev. (2021) 1–27
W. Huang, J. Berube, M. McNamara, S. Saksena, M. Hartman, T. Arshad, et al., Lymphocyte Subset Counts in COVID-19 Patients: A Meta-Analysi, .Cytom Part A. 2020;97(8):772–6.
K. Liu, T. Yang, X.F. Peng, S.M., Lv , X.L. Ye, T.S. Zhao, et al., A systematic meta-analysis of immune signatures in patients with COVID-19, Rev Med Virol. 31 (2021) 1–40.
R. Carsetti, S. Zaffina, E. Piano Mortari, S. Terreri, F. Corrente, C. Capponi, et al., Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases,. Front Immunol. 11 (2020) 1–16.
Z. Zhang, G. Ai, L. Chen, S. Liu, C. Gong, X. Zhu, et al., Associations of immunological features with COVID-19 severity: a systematic review and meta-analysis, BMC Infect Dis. 21 (2021) 1–9.
C. Zhang, J. Zhang, J. Niu , Z. Zhou, J. Zhang, Z. Tian, Interleukin-12 improves cytotoxicity of natural killer cells via upregulated expression of NKG2D, Hum Immunol. 69 (2008) 490–500.
C. Huang, Y. Wang, X. Li, L. Ren, J. Zhao, Y. Hu, et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China,. Lancet. 395 (2020) 497–506.
Y. Zhao, L. Qin, P. Zhang, K. Li, L. Liang, J. Sun, et al., Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease, JCI Insight. 5 (2020) 4–14.
M. Biswas, S. Rahaman, T.K. Biswas, Z. Haque, B. Ibrahim, Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis, Intervirology. 64 (2021) 36–47.
R.L. Luporini, J.M. Rodolpho, L.T. Kubota, A.C.M.B. Martin, M.R. Cominetti, F. Anibal, et al., IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19, Cytokine 143 (2021).
V. Mxinwa, P.V. Dludla, T.M. Nyambuya, K. Mokgalaboni, S.E. Mazibuko-mbeje, B.B. Nkambule, Natural killer cell levels in adults living with type 2 diabetes?: a systematic review and meta-analysis of clinical studies, BMC Immunol. 21(2020) 51-70.
W. De Jager, K. Bourcier, G.T. Rijkers, B.J. Prakken, V. Seyfert-Margolis, Prerequisites for cytokine measurements in clinical trials with multiplex immunoassay, BMC Immunol. 10 (2009).