scholarly journals Association of inflammatory markers with severity of disease and mortality in COVID-19 patients: a systematic review and meta-analysis

Author(s):  
Sara Khan ◽  
Pinki Mishra ◽  
Rizwana Parveen ◽  
Ram Bajpai ◽  
Mohd Ashif Khan ◽  
...  

Purpose: Literature suggests association of inflammatory markers with the severity and mortality related to COVID-19, but there are varying conclusions available. We aimed to provide an overview of the association of inflammatory markers with the severity and mortality of COVID-19 patients. Methods: We searched Medline (via PubMed), Cochrane, Clinicaltrials.gov databases until Sept 1, 2020. Results: A total of 21 studies comprising 4023 patients with COVID-19 were included in our analysis. Levels of IL-6 (WMD=18.17 95%CI 3.38 to 32.96, p=0.016), IL-8 (WMD=12.09 95%CI 4.41 to 19.77, p=0.002), MCP-1 (WMD=146.66 95%CI 88.16 to 205.16, p<0.001), CRP (WMD=31.09 95%CI 10.08 to 52.10, p=0.004), PCT (WMD= -31.23 95%CI -37.70 to -24.76, p<0.001), IL-2R (WMD=861.93 95%CI 275.45 to 1448.41, p=0.004), ferritin (WMD= 1083.34 95%CI 431.99 to 1734.70, p=0.001) were found significantly higher in the severe group compared with the non-severe group of COVID-19 patients. Moreover, non-survivors had a higher levels of IL-2R (WMD= -666.06 95%CI -782.54 to -549.59, p<0.001), IL-8 (WMD= -26.63 95%CI -33.031 to -20.236, p<0.001), IL-10 (WMD= -7.60 95%CI -8.93 to -6.26, p<0.001), TNF-α (WMD= -4.60 95%CI -5.71 to -3.48, p<0.001), IL- 1β (WMD=22.66 95%CI 8.13 to 37.19, p=0.002), CRP (WMD= -96.40 95%CI -117.84 to -74.97, p<0.001), and ferritin (WMD= -937.60 95%CI -1084.15 to -791.065, p<0.001) when compared to the non-survivor group. Conclusion: This meta-analysis highlights the association of inflammatory markers with the severity and mortality of COVID-19 patients. Measurement of these inflammatory markers may assist clinicians to monitor and evaluate the severity and prognosis of COVID-19 thereby reducing the mortality rate. Keywords: inflammatory markers, cytokine storm, interleukin, disease severity, COVID-19

Author(s):  
Mahdi Vajdi ◽  
Mahsa Mahmoudi-Nezhad ◽  
Mahdieh Abbasalizad Farhangi

Abstract. Data about the effects of alpha-lipoic acid (ALA) supplementation on inflammatory markers are inconsistent. This systematic review and dose-response meta-analysis of randomized controlled trials was performed to summarize the effects of ALA supplementation on inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to February 2020. Among all of the eligible studies, 20 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran’s Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eligible studies with a total sample size of 947 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced CRP (WMD: −0.69 mg/L, 95% CI: −1.13, −0.26, P=0.002), IL-6 (WMD: −1.83 pg/ml, 95% CI: −2.90, −0.76, P=0.001), and TNF-α concentrations (WMD: −0.45 pg/ml, 95% CI: −0.85, −0.04, P=0.032). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on serum CRP, IL-6 and TNF-α concentration. In subgroup analysis, ALA dosage, baseline concentrations of the parameter, sample size, and gender were considered as possible sources of heterogeneity. In summary, ALA supplementation improves inflammatory markers without any evidence of non-linear association to dose or duration of the trial.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2327
Author(s):  
Omid Asbaghi ◽  
Damoon Ashtary-Larky ◽  
Reza Bagheri ◽  
Parisa Moosavian ◽  
Behzad Nazarian ◽  
...  

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: −0.59 mg/L, 95% CI −0.85 to −0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: −0.12, 95% CI −0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: −0.18, 95% CI −0.86 to 0.49 pg/mL, p = 0.594). The dose–response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.


2020 ◽  
Author(s):  
Zhenlu Li ◽  
Qianqiu Che ◽  
Mao Li ◽  
Jianping Liu ◽  
Rao Du ◽  
...  

Abstract Background Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used to treat patients with 2019 coronavirus disease (COVID-19). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.


2021 ◽  
Author(s):  
Zhenlu Li ◽  
Qianqiu Che ◽  
Mao Li ◽  
Jianping Liu ◽  
Rao Du ◽  
...  

Abstract Background Tocilizumab (TCZ) is an anti-interleukin-6 antibody that has been used to treat patients with 2019 coronavirus disease (COVID-19). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.


2020 ◽  
Author(s):  
Seshadri Reddy Varikasuvu ◽  
Naveen Dutt ◽  
Saurabh Varshney ◽  
Shahir Asfahan ◽  
Paresh P. Kulkarni ◽  
...  

Author(s):  
Rafael Paschoal ESTEVES LIMA ◽  
Andressa Rafaela Silva ATANAZIO ◽  
Fernando Oliveira COSTA ◽  
Fabiano Araújo CUNHA ◽  
Lucas Guimarães ABREU

Author(s):  
Panagiotis Paliogiannis ◽  
Arduino Aleksander Mangoni ◽  
Michela Cangemi ◽  
Alessandro Giuseppe Fois ◽  
Ciriaco Carru ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t =  − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t =  − 2.77, p = 0.008) and C-reactive protein (t =  − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.


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