The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

doi:10.1016/j.lfs.2020.118167

Meta-Analysis

. 2020 Oct 1:258:118167.

doi: 10.1016/j.lfs.2020.118167. Epub 2020 Jul 29.

The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

Hamed Akbari¹, Reza Tabrizi², Kamran B Lankarani², Hamid Aria³, Sina Vakili⁴, Fatemeh Asadian⁵, Saam Noroozi⁶, Pedram Keshavarz⁷, Sanaz Faramarz⁸

Affiliations

¹ Department of Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
² Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Bioinformatics and Computational Biology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
⁵ Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
⁶ Department of Biochemistry, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.
⁷ Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁸ Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: sanaz.faramarz68@gmail.com.

PMID: 32735885
PMCID: PMC7387997
DOI: 10.1016/j.lfs.2020.118167

Free PMC article

Meta-Analysis

The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

Hamed Akbari et al. Life Sci. 2020.

Free PMC article

. 2020 Oct 1:258:118167.

doi: 10.1016/j.lfs.2020.118167. Epub 2020 Jul 29.

Authors

Hamed Akbari¹, Reza Tabrizi², Kamran B Lankarani², Hamid Aria³, Sina Vakili⁴, Fatemeh Asadian⁵, Saam Noroozi⁶, Pedram Keshavarz⁷, Sanaz Faramarz⁸

Affiliations

¹ Department of Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
² Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Bioinformatics and Computational Biology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁴ Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
⁵ Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
⁶ Department of Biochemistry, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.
⁷ Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
⁸ Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: sanaz.faramarz68@gmail.com.

PMID: 32735885
PMCID: PMC7387997
DOI: 10.1016/j.lfs.2020.118167

Abstract

Aims: This study aimed to make a comparison between the clinical laboratory-related factors, complete blood count (CBC) indices, cytokines, and lymphocyte subsets in order to distinguish severe coronavirus disease 2019 (COVID-19) cases from the non-severe ones.

Materials and methods: Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I² statistic were used to determine heterogeneity. We used the random-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs).

Key findings: Out of a total of 8557 initial records, 44 articles (50 studies) with 7865 patients (ranging from 13 to 1582), were included. Our meta-analyses with random-effect models showed a significant decrease in lymphocytes, monocyte, CD4+ T cells, CD8+ T cells, CD3 cells, CD19 cells, and natural killer (NK) cells and an increase in the white blood cell (WBC), neutrophils, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP)/hs-CRP, erythrocyte sedimentation rate (ESR), ferritin, procalcitonin (PCT), and serum amyloid A (SAA), interleukin-2 (IL-2), IL-2R, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (INF-γ) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1β, IL-17, and CD4/CD8 T cell ratio between the two groups.

Significance: Decrease in total lymphocytes and lymphocyte subsets as well as the elevation of CRP, ESR, SAA, PCT, ferritin, and cytokines, but not IL-1β and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.

Keywords: COVID-19; Cytokine; Laboratory findings; Lymphocyte subsets; Meta-analysis; Novel coronavirus; SARS-CoV-2.

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Conflict of interest statement

Declaration of competing interest None.

Figures

Unlabelled Image — **Graphical abstract**

**Fig. 1**
The flowchart of study identification and study selection process.

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References

1. Forouzesh M., Rahimi A., Valizadeh R., Dadashzadeh N., Mirzazadeh A. Clinical display, diagnostics and genetic implication of novel coronavirus (COVID-19) epidemic. Eur. Rev. Med. Pharmacol. Sci. 2020;24:4607–4615. - PubMed
1. Vakili S., Akbari H., Ghahramani S., Jamalnia S. 2020. Report of an Iranian COVID-19 Case in a Laparoscopic Cholecystectomy Patient: Case Report and Insights. - DOI
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[1] Forouzesh M., Rahimi A., Valizadeh R., Dadashzadeh N., Mirzazadeh A. Clinical display, diagnostics and genetic implication of novel coronavirus (COVID-19) epidemic. Eur. Rev. Med. Pharmacol. Sci. 2020;24:4607–4615. - PubMed

[2] Forouzesh M., Rahimi A., Valizadeh R., Dadashzadeh N., Mirzazadeh A. Clinical display, diagnostics and genetic implication of novel coronavirus (COVID-19) epidemic. Eur. Rev. Med. Pharmacol. Sci. 2020;24:4607–4615. - PubMed

[3] Vakili S., Akbari H., Ghahramani S., Jamalnia S. 2020. Report of an Iranian COVID-19 Case in a Laparoscopic Cholecystectomy Patient: Case Report and Insights. - DOI

[4] Vakili S., Akbari H., Ghahramani S., Jamalnia S. 2020. Report of an Iranian COVID-19 Case in a Laparoscopic Cholecystectomy Patient: Case Report and Insights. - DOI

[5] COVID-19 coronavirus pandemic, (n.d.). https://www.worldometers.info/coronavirus/.

[6] COVID-19 coronavirus pandemic, (n.d.). https://www.worldometers.info/coronavirus/.

[7] Ye Q., Wang B., Mao J. The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. J. Inf. Secur. 2020;80:607–613. doi: 10.1016/j.jinf.2020.03.037. - DOI - PMC - PubMed

[8] Ye Q., Wang B., Mao J. The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. J. Inf. Secur. 2020;80:607–613. doi: 10.1016/j.jinf.2020.03.037. - DOI - PMC - PubMed

[9] Wang W., He J., Wu S. 2020. The Definition and Risks of Cytokine Release Syndrome-like in 11 COVID-19-infected Pneumonia Critically Ill Patients: Disease Characteristics and Retrospective Analysis. Medrxiv. - PMC - PubMed

[10] Wang W., He J., Wu S. 2020. The Definition and Risks of Cytokine Release Syndrome-like in 11 COVID-19-infected Pneumonia Critically Ill Patients: Disease Characteristics and Retrospective Analysis. Medrxiv. - PMC - PubMed

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The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

Affiliations

The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

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