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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.

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-?), and interferon-gamma (INF-?) in the severe group compared to the non-severe group. However, no significant differences were found in IL-1?, 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-1? and IL-17, were closely associated with COVID-19 severity, implying reliable indicators of severe COVID-19.

SUBMITTER: Akbari H

PROVIDER: S-EPMC7387997 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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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.

Akbari Hamed H Tabrizi Reza R Lankarani Kamran B KB Aria Hamid H Vakili Sina S Asadian Fatemeh F Noroozi Saam S Keshavarz Pedram P Faramarz Sanaz S

Life sciences 20200729

<h4>Aims</h4>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.<h4>Materials and methods</h4>Relevant studies were searched in PubMed, Embase, Scopus, and Web of Science databases until March 31, 2020. Cochrane's Q test and the I<sup>2</sup> statistic were used to determine heterogeneity. We us ...[more]

PMID: 32735885

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Project description:PurposeA series of complications caused by severe COVID-19 can significantly affect short-term results. Therefore, early diagnosis is essential for critically COVID-19 patients. we aimed to investigate the correlation among D-dimer levels, lymphocyte subsets, cytokines, and disease severity in COVID-19 patients.MethodsSystematic review and meta- analysis of PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Embase, clinical trials, and China National Knowledge Infrastructure (CNKI) until 1 August 2022. We considered case-control, and cohort studies that compared laboratory parameters between patients with severe or non-serious diseases or between survivors and non-survivors. Pooled data was assessed by use of a random-effects model and used I 2 to test heterogeneity. We assessed the risk of bias using the Newcastle- Ottawa Scale.ResultsOf the 5,561 identified studies, 32 were eligible and included in our analysis (N = 3,337 participants). Random-effect results indicated that patients with COVID-19 in severe group had higher levels for D-dimer (WMD = 1.217 mg/L, 95%CI=[0.788, 1.646], P < 0.001), neutrophil-to-lymphocyte ratio (NLR) (WMD = 6.939, 95%CI = [4.581, 9.297], P < 0.001), IL-2 (WMD = 0.371 pg/ml, 95%CI = [-0.190, 0.932], P = 0.004), IL-4 (WMD = 0.139 pg/ml, 95%CI = [0.060, 0.219], P = 0.717), IL-6 (WMD = 44.251 pg/ml, 95%CI = [27.010, 61.493], P < 0.001), IL-10 (WMD = 3.718 pg/ml, 95%CI = [2.648, 4.788], P < 0.001) as well as lower levels of lymphocytes (WMD = -0.468( × 109/L), 95%CI = [-0.543, -0.394], P < 0.001), T cells (WMD = -446.746(/μL), 95%CI = [-619.607, -273.885], P < 0.001), B cells (WMD = -60.616(/μL), 95%CI = [-96.452, -24.780], P < 0.001), NK cells (WMD = -68.297(/μL), 95%CI = [-90.600, -45.994], P < 0.001), CD3+T cells (WMD = -487.870(/μL), 95%CI = [-627.248, -348.492], P < 0.001), CD4+T cells (WMD = -290.134(/μL), 95%CI = [-370.834, -209.435], P < 0.001), CD8+T cells (WMD = -188.781(/μL), 95%CI = [-227.806, -149.757], P < 0.001).ConclusionsThere is a correlation among higher levels of D-dimer, cytokines, lower levels of lymphocyte subsets, and disease severity in COVID-19 patients. These effective biomarkers may help clinicians to evaluate the severity and prognosis of COVID-19. This study is registered with PROSPERO, number CRD42020196659.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=196659; PROSPERO registration number: CRD42020196659.

Project description:BackgroundPrognostic factors for the Coronavirus disease 2019 (COVID1-9) are not well established. This study aimed to summarize the available data on the association between the severity of COVID-19 and common hematological, inflammatory and biochemical parameters.MethodsEMBASE, MEDLINE, Web of sciences were searched to identify all published studies providing relevant data. Random-effects meta-analysis was used to pool effect sizes.ResultsThe bibliographic search yielded 287 citations, 31 of which were finally retained. Meta-analysis of standardized mean difference (SMD) between severe and non-severe COVID-19 cases showed that CK-MB (SMD = 0.68,95%CI: 0.48;0.87; P-value:< 0.001), troponin I (SMD = 0.71, 95%CI:0.42;1.00; P-value:< 0.001), D-dimer (SMD = 0.54,95%CI:0.31;0.77; P-value:< 0.001), prothrombin time (SMD = 0.48, 95%CI:0.23;0.73; P-value: < 0.001), procalcitonin (SMD = 0.72, 95%CI: 0.34;1,11; P-value:< 0.001), interleukin-6 (SMD = 0.93, 95%CI: 0.25;1.61;P-value: 0.007),C-reactive protein (CRP) (SMD = 1.34, 95%CI:0.83;1.86; P-value:< 0.001), ALAT (SMD = 0.53, 95%CI: 0.34;0,71; P-value:< 0.001), ASAT (SMD = 0.96, 95%CI: 0.58;1.34; P-value: < 0.001), LDH (SMD = 1.36, 95%CI: 0.75;1.98; P-value:< 0.001), CK (SMD = 0.48, 95%CI: 0.10;0.87; P-value:0.01), total bilirubin (SMD = 0.32, 95%CI: 0.18;0.47;P-value: < 0.001), γ-GT (SMD = 1.03, 95%CI: 0.83;1.22; P-value: < 0.001), myoglobin (SMD = 1.14, 95%CI: 0.81;1.47; P-value:< 0.001), blood urea nitrogen (SMD = 0.32, 95%CI: 0.18;0.47;P-value:< 0.001) and Creatininemia (SMD = 0.18, 95%CI: 0.01;0.35; P-value:0.04) were significantly more elevated in severe cases, in opposition to lymphocyte count (SMD = -0.57, 95%CI:-0.71; - 0.42; P-value: < 0.001) and proportion of lymphocytes (SMD = -0.81, 95%CI: - 1.12; - 0.49; P-value:< 0.001) which were found to be significantly lower in severe patients with other biomarker such as thrombocytes (SMD = -0.26, 95%CI: - 0.48; - 0.04; P-value:0.02), eosinophils (SMD = - 0.28, 95%CI:-0.50; - 0.06; P-value:0.01), haemoglobin (SMD = -0.20, 95%CI: - 0.37,-0.03; P-value:0.02), albuminemia (SMD-1.67,95%CI -2.40; - 0.94; P-value:< 0.001), which were also lower. Furthermore, severe COVID-19 cases had a higher risk to have lymphopenia (RR =1.66, 95%CI: 1.26;2.20; P-value:0.002), thrombocytopenia (RR = 1.86, 95%CI: 1.59;2.17; P-value: < 0.001), elevated procalcitonin level (RR = 2.94, 95%CI: 2.09-4.15; P-value:< 0.001), CRP (RR =1.41,95%CI: 1.17-1.70; P-value:0.003), ASAT(RR =2.27, 95%CI: 1.76;2.94; P-value:< 0.001), CK(RR = 2.61, 95%CI: 1.35;5.05; P-value: 0.01), Creatininemia (RR = 3.66, 95%CI: 1.53;8.81; P-value: 0.02) and LDH blood level (RR = 2.03, 95%CI: 1.42;290; P-value: 0.003).ConclusionSome inflammatory (procalcitonin, CRP), haematologic (lymphocyte, Thrombocytes), and biochemical (CK-MB, Troponin I, D-dimer, ASAT, ALAT, LDH, γ-GT) biomarkers are significantly associated with severe COVID-19. These biomarkers might help in prognostic risk stratification of patients with COVID-19.

Project description:BackgroundCOVID-19 was first identified in Wuhan, China, in December 2019, spreading to the rest of the globe, becoming a pandemic. Some studies have shown an association between pregnancy status and severe COVID-19 with a cytokine storm, whereas others have shown contrasting results.ObjectiveThe aim of this study was to examine the relationship between pregnancy status and the clinical COVID-19 severity characterized by the cytokine storm through a systematic review and meta-analysis.MethodsWe searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting pregnancy status and comparing the COVID-19 severity cytokine storm outcome were included. COVID-19 severity characterized by a cytokine storm was described using parameters such as intensive care unit admission, invasive mechanical ventilation, mechanical ventilation, hospital admission, pro- and anti-inflammatory cytokine levels, consolidation on chest computed tomography scan, pulmonary infiltration, extreme fevers as characteristic of a cytokine storm, syndromic severity, higher neutrophil count indicative of a cytokine storm, and severe COVID-19 presentation.ResultsA total of 17 articles including data for 840,332 women with COVID-19 were included. This meta-analysis revealed a correlation between positive pregnancy status and severe COVID-19 with a cytokine storm (random-effects model odds ratio [OR] 2.47, 95% CI 1.63-3.73; P<.001), with a cumulative incidence of 6432 (14.1%) and 24,352 (3.1%) among pregnant and nonpregnant women with COVID-19, respectively. The fixed-effects model also showed a correlation between pregnancy status and severe COVID-19 with a cytokine storm (OR 7.41, 95% CI 7.02-7.83; P<.001). Considerable heterogeneity was found among all pooled studies (I²=98%, P<.001). Furthermore, the updated analysis showed substantially low heterogeneity (I²=29 %, P=.19), and the funnel plot revealed no publication bias. The subanalysis between single-center and multicenter studies demonstrated similar heterogeneity (I2=72% and 98%, respectively). Sensitivity analysis on each subgroup revealed that pregnancy was significantly related to severe COVID-19 with a cytokine storm from single-center studies (fixed-effects model OR 3.97, 95% CI 2.26-6.95; P<.001) with very low heterogeneity (I²=2%, P=.42).ConclusionsBeing pregnant is clearly associated with experiencing a severe course of COVID-19 characterized by a cytokine storm. The COVID-19 pandemic should serve as an impetus for further research on pregnant women diagnosed with COVID-19 to map out the salient risk factors associated with its severity.Trial registrationPROSPERO CRD42021242011; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242011.

Dataset Information

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

Publications

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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