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

Life Sci. 2020 Oct 1:258:118167. doi: 10.1016/j.lfs.2020.118167. Epub 2020 Jul 29.

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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Betacoronavirus / immunology
  • Betacoronavirus / isolation & purification
  • CD4-CD8 Ratio
  • COVID-19
  • Coronavirus Infections / blood*
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / immunology
  • Cytokines / blood*
  • Cytokines / immunology
  • Humans
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Pandemics
  • Pneumonia, Viral / blood*
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / immunology
  • Prognosis
  • SARS-CoV-2

Substances

  • Cytokines