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, Reza Tabrizi, Kamran B Lankarani, Hamid Aria, Sina Vakili, Fatemeh Asadian, Saam Noroozi, Pedram Keshavarz, Sanaz Faramarz

Journal: Life sciences 2020;258():118167

PMID: 32735885

Plain Language Summary

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Literature shows that lymphopenia [reduced level of the blood cell lymphocyte] and cytokine release syndrome are among the characteristics caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - the new infectious Coronavirus Disease 2019 (COVID-19). The main aims of this study were (a) to analyse the different characteristics of cytokine levels, lymphocyte subsets, complete blood count (CBC) indices, and a number of infection-related factors between mild/moderate and severe/critical patients, and (b) to screen out suitable indicators for the prediction of the disease severity in order to provide some insight into the subsequent clinical interventions. This study is a systemic review and meta-analysis of 50 studies (44 articles) with a total of 7865 patients including 2286 in the severe group and 5579 in the non-severe group. Results demonstrated a significant lymphopenia in severe/critical infected cases compared to mild/moderate COVID-19 ones across 46 studies. The severity of COVID-19 has also a significant, positive association with a number of infection related factors (such as C-reactive protein) and ferritin levels. Moreover, with respect to CBC indices, the findings revealed significantly higher levels in white blood cells and neutrophil, while lower lymphocyte and monocyte levels in severe than in non-severe confirmed COVID-19 patients. Authors conclude that it is essential that clinicians have access to reliable quick pathogen tests and feasible differential diagnoses based on the clinical descriptions in their first contact with suspected patients.

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 I 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.

Copyright © 2020 Elsevier Inc. All rights reserved.

Address: 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.; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.; 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.; Biochemistry Department, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.; Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.; Department of Biochemistry, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.; Medical Imaging Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.; Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: [email protected].

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