Anakinra was not associated with lower mortality in hospitalised COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials

The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of anakinra on mortality in patients with COVID-19. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of COVID-19 with anakinra, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Five Randomized controlled trials (enrolling 1859 participants) met the inclusion criteria. There was no statistically significant difference in 14-day mortality (RR 0.78, 95% CI 0.43–1.39; P = 0.40), 28-day mortality (RR 1.06, 95% CI 0.89–1.26; P = 0.51), and 90-day mortality (RR 1.01, 95% CI 0.73–1.39; P = 0.97) between the two groups. Sensitivity analyses further confirmed these results. Anakinra was not associated with reduced mortality in hospitalised patients with COVID-19. Anakinra probably should not be used routinely in COVID-19 patients.     

Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis

Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (−3.7 g/L, 95% CI, −5.3 to −2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.     

Effect of COVID-19 vaccination on semen parameters: A systematic review and meta-analysis

The aim of this study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on semen parameters through systematic review and meta-analysis. PubMed, EMBASE, Web of Science, and Cochrane Library were comprehensively searched by June 2022. Studies were considered eligible if they compared semen parameters before and after COVID-19 vaccination or between vaccinated and unvaccinated men, with no restrictions on vaccine types or doses. The effect size was calculated as mean difference (MD) with 95% confidence interval (CI) using a random-effects model. Subgroup and sensitivity analyses were conducted to assess the sources of heterogeneity measured by the I² statistic, with publication bias evaluated by Egger's test. Twelve cohort studies involving 914 participants fulfilled the inclusion criteria. In a comparison of vaccinated versus unvaccinated group, the pooled data revealed no significant differences in semen volume (MD = 0.18 ml, 95% CI −0.02 to 0.38), sperm concentration (MD = 1.16 million/ml, 95% CI −1.34 to 3.66), total sperm motility (MD = −0.14%, 95% CI −2.84 to 2.56), progressive sperm motility (MD = −1.06%, 95% CI −2.88 to 0.77), total sperm count (MD = 5.92 million, 95% CI −10.22 to 22.05), total motile sperm count (MD = 2.18 million, 95% CI −1.28 to 5.63), total progressively motile sperm count (MD = −3.87 million, 95% CI −13.16 to 5.43), and sperm morphology (MD = 0.07%, 95% CI −0.84 to 0.97). The results also remained similar across messenger ribonucleic acid, viral-vector, and inactivated COVID-19 vaccines. Sensitivity analysis identified two individual studies that contributed to heterogeneity, while the effect size was not materially altered. No obvious publication bias was detected among included studies. Our finding suggested that COVID-19 vaccination had no detrimental impact on semen quality, which could be potentially helpful to reduce male vaccine hesitancy and increase vaccination coverage.     

COVID-19 and liver dysfunction: A systematic review and meta-analysis of retrospective studies

Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.     

The effect of adherence to high-quality dietary pattern on COVID-19 outcomes: A systematic review and meta-analysis

Dietary quality and patterns may influence SARS-CoV-2 infection and outcomes, but scientific data and evidence to support such a role are lacking. Therefore, this meta-analysis aims to elucidate the effect of prepandemic diet quality on the risk of COVID-19 infection and hospitalization. PubMed/MEDLINE, CENTRAL, Scopus, and EMBASE were systematically searched for articles published up to September 1, 2022. A systematic review and meta-analysis were performed to calculate each outcome's risk ratio (RR) and 95% confidence interval (CI). Five studies including 4 023 663 individuals (3 149 784 high-quality diet individuals and 873 881 controls) were included in the present meta-analysis. The effectiveness of high-quality dietary pattern against SARS-CoV-2 infection and hospitalization was 28% (95% CI 19%–36%) and 62% (95% CI 25%–80%); respectively. Subgroup analysis based on different levels of diet quality showed no difference between middle and high levels of diet quality in reducing the risk of COVID-19 infection. Interestingly, subgroup analysis based on the different types of high-quality diets and the risk of COVID-19 infection revealed that the effectiveness of plant-based diet against SARS-CoV-2 infection was 50% (95% CI 30%–65%); while the effectiveness of Mediterranean diet against SARS-CoV-2 infection was 22% (95% CI 12%–31%). Adherence to a high-quality dietary pattern is associated with a lower risk of COVID-19 infection and hospitalization. More studies are required to confirm these findings, and future studies should determine the biological mechanisms underlying the association between diet quality and risk of COVID-19 infection.     

Respiratory viral co-infections in patients with COVID-19 and associated outcomes: A systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to critically assess the published literature related to community-acquired viral co-infections and COVID-19 and to evaluate the prevalence, most identified co-pathogens, and relevant risk factors. Furthermore, we aimed to examine the clinical features and outcomes of co-infected compared to mono-infected COVID-19 patients. We systematically searched PubMed, Web of Science, Embase, Scopus, and The Cochrane Library for studies published from 1 November 2019 to 13 August 2021. We included patients of all ages and any COVID-19 severity who were screened for respiratory viral co-infection within 48 h of COVID-19 diagnosis. The main outcome was the proportion of patients with a respiratory viral co-infection. The systematic review was registered to PROSPERO (CRD42021272235). Out of 6053 initially retrieved studies, 59 studies with a total of 16,643 SARS-CoV-2 positive patients were included. The global pooled prevalence was 5.01% (95% CI 3.34%–7.27%; I² = 95%) based on a random-effects model, with Influenza Viruses (1.54%) and Enteroviruses (1.32%) being the most prevalent pathogens. Subgroup analyses showed that co-infection was significantly higher in paediatric (9.39%) than adult (3.51%) patients (p-value = 0.02). Furthermore, co-infected patients were more likely to be dyspnoeic and the odds of fatality (OR = 1.66) were increased. Although a relatively low proportion of COVID-19 patients have a respiratory viral co-infection, our findings show that multiplex viral panel testing may be advisable in patients with compatible symptoms. Indeed, respiratory virus co-infections may be associated with adverse clinical outcomes and therefore have therapeutic and prognostic implications.     

Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of “time to clinical cure,” “virological cure,” “death or clinical worsening of disease,” “radiological progression,” and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in “time to body temperature normalization” and one study reported less “cough days” in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.     

Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19

To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1β (IL-1β), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF)-α, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1β, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-α, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1β was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.     

Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO₂ (r_s= 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.     

A meta-analysis of the association between Caesarean section and childhood asthma

Background Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting. Objective To review published literature and perform a meta‐analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma. Methods MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta‐analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies. Results Twenty‐three studies were identified. The overall meta‐analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I²=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I²=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6). Conclusion In this meta‐analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.     

Epidemiologic characteristics of cases with reinfection,recurrence, and hospital readmission due to COVID-19: A systematic review and meta-analysis

Recent studies reported that some recovered COVID-19 patients have tested positive for virus nucleic acid again. A systematic search was performed in Web of Science, PubMed, Scopus, and Google Scholar up to March 6, 2021. The pooled estimation of reinfection, recurrence, and hospital readmission among recovered COVID-19 patients was 3, 133, and 75 per 1000 patients, respectively. The overall estimation of reinfection among males compared to females was greater. The prevalence of recurrence in females compared to males was more common. Also, hospital readmission between sex groups was the same. There is uncertainty about long-term immunity after SARS-Cov-2 infection. Thus, the possibility of reinfection and recurrence after recovery is not unexpected. In addition, there is a probability of hospital readmission due to adverse events of COVID-19 after discharge. However, with mass vaccination of people and using the principles of prevention and appropriate management of the disease, frequent occurrence of the disease can be controlled.     

Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta-analyses were conducted to determine the associations between IL17A rs8193036 (−737C/T), rs2275913 (−197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta-analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR] = 1.490, 95% confidence interval [CI] = 1.027–2.161, p = .036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta-analysis. This meta-analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility.     

Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis

Currently approved therapies for COVID-19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in-hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID-19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta-analysis to assess the effect of quercetin on clinical outcomes in COVID-19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random-effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10–0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10–0.62) but did not decrease the risk of all-cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID-19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large-scale RCTs are needed to confirm these findings.     

Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19

The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated 43 adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin-6 (IL-6), d -dimer (d -D), glucose, thrombin time, fibrinogen, and C-reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL-6 were 24.3 and 0.795 µg/L, respectively, while those of d -D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL-6 combined with d -D was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and d -D tandem testing was up to 93.3%, while the sensitivity of IL-6 and d -D by parallel test in the severe COVID-19 was 96.4%. IL-6 and d -D were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value.     

COVID-19 patients' clinical characteristics,discharge rate,and fatality rate of meta-analysis

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).     

COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis

The susceptibility, risk factors, and prognosis of COVID-19 in patients with inflammatory bowel disease (IBD) remain unknown. Thus, our study aims to assess the prevalence and clinical outcomes of COVID-19 in IBD. We searched PubMed, EMBASE, and medRxiv from 2019 to 1 June 2022 for cohort and case-control studies comparing the prevalence and clinical outcomes of COVID-19 in patients with IBD and in the general population. We also compared the outcomes of patients receiving and not receiving 5-aminosalicylates (ASA), tumour necrosis factor antagonists, biologics, systemic corticosteroids, or immunomodulators for IBD. Thirty five studies were eligible for our analysis. Pooled odds ratio of COVID-19-related hospitalisation, intensive care unit (ICU) admission, or death in IBD compared to in non-IBD were 0.58 (95% confidence interval (CI) = 0.28–1.18), 1.09 (95% CI = 0.27–4.47), and 0.67 (95% CI = 0.32–1.42), respectively. Inflammatory bowel disease was not associated with increased hospitalisation, ICU admission, or death. Susceptibility to COVID-19 did not increase with any drugs for IBD. Hospitalisation, ICU admission, and death were more likely with 5-ASA and corticosteroid use. COVID-19-related hospitalisation (Odds Ratio (OR): 0.53; 95% CI = 0.38–0.74) and death (OR: 0.13; 95% CI = 0.13–0.70) were less likely with Crohn's disease than ulcerative colitis (UC). In conclusion, IBD does not increase the mortality and morbidity of COVID-19. However, physicians should be aware that additional monitoring is needed in UC patients or in patients taking 5-ASA or systemic corticosteroids.