scholarly journals Association of immunological features with COVID-19 severity: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Zhicheng Zhang ◽  
Guo Ai ◽  
Liping Chen ◽  
Shunfang Liu ◽  
Chen Gong ◽  
...  

Abstract Background: We aim to explore the association of immunological features with COVID-19 severity.Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of some immune cells, CD3+ T cell (×106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (×106, MD, -203.56; 95%CI, -277.94 to -129.18), CD8+ T cell (×106, MD, -128.88; 95%CI, -163.97 to -93.79), B cell (×106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (×106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of some cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of some chemokines, MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant differences were found in other indicators, Treg cell (×106, MD, -0.13; 95%CI, -1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, -0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, -0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, -2.88 to 4.75).Conclusion: Our meta-analysis revealed significant lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), significant higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and significant higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhicheng Zhang ◽  
Guo Ai ◽  
Liping Chen ◽  
Shunfang Liu ◽  
Chen Gong ◽  
...  

Abstract Background COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. Methods We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. Results A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4+ T cell (× 106, MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8+ T cell (× 106, MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 106/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 106/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75). Conclusion Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.


2020 ◽  
Author(s):  
Zhicheng Zhang ◽  
Guo Ai ◽  
Liping Chen ◽  
Shunfang Liu ◽  
Chen Gong ◽  
...  

Abstract BackgroundWe aim to explore the association of immunological features with COVID-19 severity.MethodsWe conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed and Web of Science.ResultsA total of 16 studies with 1689 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells, CD3+ T cell (× 106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (× 106, MD, -225.89; 95%CI, -306.36 to -145.43), CD8+ T cell (× 106, MD, -138.59; 95%CI, -176.36 to -100.82), B cell (× 106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (× 106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75). However, no significant differences were found in other indicators, IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), Treg cell (× 106, MD, -0.13; 95%CI, -1.40 to 1.14), and CD4+/CD8+ ratio (MD, 0.17; 95%CI, -0.14 to 0.49).ConclusionOur meta-analysis revealed significant lower levels in immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells) and significant higher levels in cytokines (TNF-α, IL-5, IL-6 and IL-10) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253968
Author(s):  
Bowen Li ◽  
Yifeng Xu ◽  
Cailian Lu ◽  
Zhenheng Wei ◽  
Yongyue Li ◽  
...  

Background Recently, increasing attention has been paid to the periodontal health of orthodontic patients in the maintenance stage in clinical practice. The focus of this meta-analysis was to compare the effects of vacuum-formed retainers (VFR) and Hawley retainers (HR) on periodontal health, in order to provide a reference for clinical selection. Methods From the establishment of the database until November 2020, a large number of databases were searched to find relevant randomized control trials, including the Cochrane Library databases, Embase, PubMed, Medline via Ovi, Web of Science, Scopus, Grey Literature in Europe, Google Scholar and CNKI. Related literature was manually searched and included in the analysis. Two researchers screened the literature according to relevant criteria. The size of the effect was determined using RevMan5.3 software, and the mean difference and 95% confidence intervals (CI) were used to estimate the results using a random effects model. Results This meta-analysis included six randomized controlled trials involving 304 patients. The results of the meta-analysis showed that there was no statistical difference in sulcus probing depth status between the VFR group and the HR group, including at 1, 3, and 6 months. Compared with the VFR group, the HR group showed a lower gingival index at 1 month (mean difference = 0.12, 95%CI: 0.06 to 0.19) and 3 months (mean difference = 0.11, 95%CI: 0.06 to 0.17), while there was no statistically significant difference at 6 months (mean difference = 0.10, 95%CI: -0.07 to 0.27). The plaque index of the HR group also showed a good state at 1 month (mean difference = 0.06, 95%CI: 0.01 to 0.12), 3 months (mean difference = 0.12, 95%CI: 0.08 to 0.16), and 6 months (mean difference = 0.19, 95%CI: 0.09 to 0.29). Subgroup analysis of PLI showed that when all teeth were measured, PLI status was lower in the HR group at 6 months (mean difference = 0.32, 95%CI: 0.18 to 0.46). PLI status was also low for the other teeth group (mean difference = 0.15, 95%CI: 0.08 to 0.22). Conclusion Our meta-analysis showed that patients using the Hawley retainer had better periodontal health compared with those using vacuum-formed retainers. However, more research is needed to look at the periodontal health of patients using these two retainers.


2016 ◽  
Author(s):  
Gyanesh Singh ◽  
Hasan Korkaya

Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.


2016 ◽  
Author(s):  
Gyanesh Singh ◽  
Hasan Korkaya

Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.


Author(s):  
Zhili Wang ◽  
Yu He ◽  
zhengxiu luo

Abstract Objective: To evaluate the discriminative ability of laboratory abnormalities between general mycoplasma pneumoniae pneumonia (GMPP) and refractory MPP (RMPP) in children. Methods: An electronic search in PubMed, Web of Science, Embase, and Cochrane Library was performed to identify studies reporting on laboratory abnormalities in children with GMPP and RMPP. Data were independently extracted by two reviewers. Meta-analyses within the random-effects model were used to synthesize data. Effect sizes were calculated as standardized mean differences (SMD) or weighted mean difference (WMD). The Newcastle-Ottawa Scale (NOS) was used to assess the methodologic quality of included studies. Results: Twenty-one articles (3,877 patients) comparing laboratory findings between patients with GMPP and RMPP were eligible for this meta-analysis. Patients with RMPP had significantly increased neutrophils, CD8+ lymphocytes, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), D-dimer, total IgA, total IgM, as well as decreased lymphocytes, hemoglobin, and albumin. Multiple inflammatory biomarkers (C-reactive protein [CRP], procalcitonin [PCT], erythrocyte sedimentation rate [ESR], ferritin, interleukin [IL]-6, IL-10, IL-17, IL-18, interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) were also markedly elevated in RMPP patients. Conclusions: Elevated levels of CD8+ lymphocytes, LDH, AST, D-dimer, total IgA, total IgM, inflammatory biomarkers (CRP, PCT, ESR, ferritin, IL-6, IL-10, IL-17, IL-18, IFN-γ, and TNF-α), and lower lymphocytes, hemoglobin, and albumin are associated with RMPP and thus may be used as early identification or even prediction of RMPP in children. Keywords: Child; Refractory Mycoplasma pneumoniae pneumonia; clinical chemistry; meta-analysis


2021 ◽  
Vol 7 (3) ◽  
pp. 205521732110323
Author(s):  
Kouichi Ito ◽  
Naoko Ito ◽  
Sudhir K Yadav ◽  
Shradha Suresh ◽  
Yong Lin ◽  
...  

Background Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells. Objective To investigate the difference in immunological parameters in response to GA20 and GA40 treatments. Methods We analyzed five pro-inflammatory cytokines (IL-1β, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20. Results Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups. Conclusions The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3358-3358 ◽  
Author(s):  
Kazusa Ishii ◽  
Haneen Shalabi ◽  
Bonnie Yates ◽  
Cindy Delbrook ◽  
Crystal L. Mackall ◽  
...  

Abstract Background: Cytokine release syndrome (CRS) in the setting of CAR T cell therapy manifests as a wide constellation of symptoms with multi-organ involvement. CRS can vary from a mild, self-limited course to a life-threatening systemic inflammatory response which, in severe cases, may be associated with manifestations similar to those seen in hemophagocytic lymphohistiocytosis (HLH). Tocilizumab, an anti-human IL-6 receptor antibody, has become a widely accepted pharmacologic intervention of first choice in severe CRS based on the observation of elevated levels of inflammatory cytokines, most notably interleukin (IL)-6 and interferon (IFN)-γ. Indeed, following administration of tocilizumab, most patients show rapid signs of improvement. However, in rare circumstances, CRS may be refractory to tocilizumab, and repeat administration or institution of additional immunosuppression is needed. Here we summarize cytokine profiles and CRS seen in patients treated with anti-CD22-CAR T cells and propose tocilizumab-refractory CRS as a potentially distinct pathophysiological entity from typical CRS that may merit alternative immunosuppressive interventions other than tocilizumab. Methods: Children and young adults with relapsed/refractory CD22+ ALL were treated with anti-CD22 CAR T cells. Serial samples for serum cytokine levels (IFN-γ, IL-6, IL-2, IL-10, IL-12p70, IL-1β, IL-15, IL-13, IL-4, IL-8, TNF-α, GM-CSF, MIP1-α) were obtained at pre-specified time points (0, 12, 24, 48, 72 hours, then daily on days 4 - 14 and 28 following CAR T cell infusion). Transduced CAR T cell dosage ranged from 3x10e5 cells/kg (dose level [DL] 1), 1x10e6 cells/kg (DL2), and 3x10e6 cells/kg (DL3). CRS severity was determined according to recently proposed grading system (Lee DW et al., Blood. 2014). Disease burden was assessed using standard morphology and flow cytometry analysis of bone marrow and peripheral blood samples. Results: Cytokine profiles are available on 10 patients treated: first 9 patients enrolled in our phase I trial (NCT02315612), and the tenth patient was treated off-protocol on an emergency investigational new drug protocol given lack of alternative treatment option for rapidly progressing disease. All subjects, median age 20 years (range, 6-22 years), had a diagnosis of multiply relapsed ALL. Seven of 10 subjects developed CRS. Five subjects with CRS were complete responders to CAR therapy (Table). The median time to the onset of CRS was 9 days (range, 7-12 days) post-infusion and resolved within 1 week with supportive care alone except in one patient who received pharmacologic intervention for grade 4 CRS. Rise in C-reactive protein (CRP) tended to correlate with clinical severity of CRS. Chronological changes in the level of IFN-γ, IL-6, IL-1β, IL-8, TNF-α, and MIP1-α generally mirrored the CRP trend, typically preceding CRP change by 1-2 days. In contrast to the CRS (maximum grade 2) seen in the first 9 patients, the 10th patient treated at DL3 developed grade 4 CRS with manifestations characteristic of HLH unresponsive to tocilizumab. Cytokine profile for this patient, compared to those of other CRS patients, was notable for a substantially higher serum IL-2 (35 pg/mL vs median 6.1 (range, 1.2-13.5)) and GM-CSF level (28 pg/mL vs median 1.0 (range, 0-6.1)) at 12 hours post infusion. Subsequent CRP elevation was not initially accompanied by a rise in IL-6 as in other patients, which may have explained the lack of response to tocilizumab (Figure). Evaluation for a genetic cause of HLH did not reveal any mutations (PRF1, MUNC13-4, RAB27A, STX11, STXBP2). Although this patient was a complete responder to therapy, the clinical course was complicated by pre-existing respiratory compromise and bacteremia, which may have contributed to increased CAR toxicity with variability in the cytokine profile. Conclusion: Based on our early experience, we postulate that patients with an early increase in GM-CSF and IL-2 may potentially experience more atypical and severe CRS, which without a concomitant rise in IL-6, may not respond to tocilizumab and thus early intervention with other immunosuppression may be indicated. Analysis of larger numbers of patients is required to better delineate clinical confounders and to develop rational pharmacological approach to CAR-mediated inflammatory responses. Ongoing efforts are underway to further analyze clinical samples for biomarkers. Disclosures Mackall: NCI: Patents & Royalties: B7H3 CAR.


2019 ◽  
Vol 147 ◽  
Author(s):  
L. V. Cooper ◽  
P. A. Kristiansen ◽  
H. Christensen ◽  
A. Karachaliou ◽  
C. L. Trotter

Abstract Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482–0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87–2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4–1.7) and during outbreaks (OR 6.7 95% CI 1.6–29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10–14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.


2019 ◽  
Vol 33 (5) ◽  
pp. 486-499 ◽  
Author(s):  
Runting Cai ◽  
Camilla Zimmermann ◽  
Monika Krzyzanowska ◽  
John Granton ◽  
Breffni Hannon

Background: Patients with advanced cancer have an elevated risk of venous thromboembolism. Increasingly, patients are admitted to palliative care settings for brief admissions, with greater numbers of discharges (vs deaths) reported internationally. There is limited guidance around the use of thromboprophylaxis or incidence of venous thromboembolism for these patients. Aim: The aim of this study was to review the use of thromboprophylaxis as well as incidence of venous thromboembolism and bleeding in palliative care units or residential hospices for patients with advanced cancer. Design: A systematic review using Cochrane methods. Data sources: Medline, Embase and the Cochrane Library were searched up to 28 September 2018 along with a grey literature search; the reference lists of selected papers were hand-searched. Inclusion criteria were original papers assessing thromboprophylaxis use in palliative care units or residential hospices for adult inpatients with cancer. Two reviewers independently selected and appraised papers using a tool designed for disparate data. Heterogeneity in study design made a meta-analysis not possible. Results: A total of 11 full-text papers (9 quantitative and 2 qualitative) and 11 abstracts were included. Thromboprophylaxis use ranged between 4% and 53%; venous thromboembolism rates between 0.5% and 20%; and bleeding incidence was between 0.01% and 9.8%. Risk assessment tools were used infrequently and adherence to international thromboprophylaxis guidelines ranged between 5% and 71%. Physician opinions differed around the use of thromboprophylaxis; patients were largely accepting of thromboprophylaxis if it was offered. Conclusion: There is limited evidence around the optimal use of thromboprophylaxis for patients with advanced cancer admitted to palliative care settings. Although some patients may derive benefit, further research in this area is warranted.


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