A meta-review of meta-analyses and an updated meta-analysis on the efficacy of chloroquine and hydroxychloroquine in treating COVID19 infection

Objective: To synthesize the findings presented in systematic reviews and meta-analyses as well as to update the evidence using a meta-analysis in evaluating the efficacy and safety of CQ and HCQ with or without Azithromycin for the treatment of COVID19 infection.Methods: The design of this meta-review followed the Preferred Reporting Items for Overviews of Systematic Reviews including harms checklist (PRIO-harms). A comprehensive search included several electronic databases in identifying all systematic reviews and metaanalyses as well as experimental studies which investigated the efficacy and safety of CQ, HCQ with or without antibiotics as COVID19 treatment. Findings from the systematic reviews and meta-analyses were reported using a structured summary including tables and forest plots. The updated meta-analysis of experimental studies was carried out using the distributional assumption-free quality effects model. Risk of bias was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool for reviews and the MethodologicAl STandard for Epidemiological Research (MASTER) scale for the experimental studies. The main outcome for both the meta-review and the updated meta-analysis was mortality. Secondary outcomes included transfer to the intensive care unit (ICU) or mechanical ventilation, worsening of illness, viral clearance and the occurrence of adverse events. Results: A total of 13 reviews with 40 primary studies comprising 113,000 participants were included. Most of the primary studies were observational (n=27) and the rest were experimental studies. Two meta-analyses reported a high risk of mortality with similar ORs of 2.5 for HCQ with Azithromycin. However, four other meta-analyses reported contradictory results with two reporting a high risk of mortality and the other two reporting no significant association between HCQ with mortality. Most reviews reported that HCQ with or without Azithromycin had no significant effect on virological cure, disease exacerbation or the risk of transfer to the ICU, need for intubation or mechanical ventilation. After exclusion of studies that did not meet the eligibility criteria, the updated meta-analysis contained eight experimental studies (7 RCTs and 1 quasiexperimental trial), with a total of 5279 participants of whom 1856 were on either CQ/HCQ or combined with Azithromycin. CQ/HCQ with or without Azithromycin was significantly associated with a higher risk of adverse events. HCQ was not effective in reducing mortality transfer to the ICU, intubation or need for mechanical ventilation virological cure (RR 1.0, 95%CI 0.9-1.2, I2 =55%, n=5 studies) nor disease exacerbation (RR 1.2, 95%CI 0.3-5.0, I2 =29%, n=3 studies). Conclusion: There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation

The prevalence of adaptive immunity to COVID-19 and reinfection after recovery - a comprehensive systematic review and meta-analysis.

This study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies and T and B memory cells after recovery. In addition, the prevalence of COVID-19 reinfection and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. A synthesis of existing research was conducted. The Cochrane Library, the China Academic Journals Full Text Database, PubMed, and Scopus, and preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. Included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity was assessed using the I and Cochran's Q statistics and publication bias was assessed using Doi plots. Fifty-four studies from 18 countries, with around 12,000,000 individuals, followed up to 8 months after recovery, were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG - 90.4% (95%CI 72.2-99.9, I = 89.0%), CD4+ - 91.7% (95%CI 78.2-97.1y), and memory B cells 80.6% (95%CI 65.0-90.2) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0-0.7, I = 98.8). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1-0.3, I = 90.5%). Around 90% of recovered individuals had evidence of immunological memory to SARS-CoV-2, at 6-8 months after recovery and had a low risk of reinfection

The delivery of obesity interventions to children and adolescents with physical disabilities: a systematic review

Background To examine the process and mechanisms of delivering obesity interventions to physically disabled children/adolescents. Methods PubMed, Medline, CINAHL Plus, Embase, Cochrane Library, Google Scholar, ClinicalTrials.gov, Science Direct were systematically and manually searched for studies conducted in physically disabled children/adolescents (0–18 years). Included interventions were physical activity, diet and obesity prevention education. Included outcomes were body mass index (BMI)/weight and obesity prevention knowledge. The Mixed Methods Appraisal Tool aided methodological quality assessments. Data were extracted and delivery models were synthesized and narratively summarized using the social ecological model. Results Seven studies of low (n = 4) and moderate (n = 3) scoring on methodological quality were eligible for inclusion. Study duration was 5 months or less (n = 5), 8 months (n = 1) and 2 years (n = 1). Interventions were delivered at home, school, hospital and rehabilitation centre through the internet, face-to-face and parents. No intervention was delivered at three or more levels of individual, interpersonal, institutional or community levels. No study reported significant outcomes on reduction in BMI/weight, or increase in obesity prevention knowledge. Conclusions Evidence reviewed in this study shows that obesity interventions for physically disabled children/adolescents lack both in delivery and design. Gaps revealed should be considered when developing interventions for this special population

The diagnostic accuracy of HbA , compared to the oral glucose tolerance test, for screening for type 2 diabetes mellitus in Africa-a systematic review and meta-analysis.

To assess the diagnostic accuracy of HbA , compared to fasting plasma glucose (FPG) and the oral glucose tolerance test (OGTT), in screening for type 2 diabetes (T2D) in Africa. We systematically searched databases for studies that compared the HbA to either the OGTT, or the FPG for T2D diagnosis were included. The QUADAS 2 tool was used for assessing the quality of included studies. We used the split component synthesis (SCS) method for the meta-analysis of diagnostic accuracy studies to pool the studies for meta-analysis of sensitivity and specificity, primarily at the HbA ≥48mmol/mol (6.5%) cut-off and at other cut-offs. We assessed heterogeneity using the I statistic and publication bias using Doi plots. Eleven studies, from seven African countries, with 12925 participants, were included. Against the OGTT, HbA ≥48mmol/mol (6.5%) had a pooled sensitivity of 57.7% (95%CI 43.4-70.9) and specificity of 92.3% (95%CI 83.9 - 96.5). Against the FPG, HbA ≥48mmol/mol (6.5%) had a pooled sensitivity of 64.5% (95%CI 50.5 - 76.4) and specificity of 94.3% (95%CI 87.9 - 97.5). The highest sensitivity for HbA , against the OGTT, was at the 42mmol/mol (6.0%) cut off. In Africa, the HbA ≥48mmol/mol (6.5%) cut-off may miss almost half of the individuals with T2D based on blood glucose measures

Efficacy of chloroquine and hydroxychloroquine in treating COVID-19 infection: A meta-review of systematic reviews and an updated meta-analysis

To synthesize findings from systematic reviews and meta-analyses on the efficacy and safety of chloroquine (CQ) and hydroxychloroquine (HCQ) with or without Azithromycin for treating COVID-19, and to update the evidence using a meta-analysis. A comprehensive search was carried out in electronic databases for systematic reviews, meta-analyses and experimental studies which investigated the efficacy and safety of CQ, HCQ with or without Azithromycin to treat COVID-19. Findings from the reviews were synthesised using tables and forest plots and the quality effect model was used for the updated meta-analysis. The main outcomes were mortality, the need for intensive care services, disease exacerbation, viral clearance and occurrence of adverse events. Thirteen reviews with 40 primary studies were included. Two meta-analyses reported a high risk of mortality, with ORs of 2.2 and 3.0, and the two others found no association between HCQ and mortality. Findings from two meta-analyses showed that HCQ with Azithromycin increased the risk of mortality, with similar ORs of 2.5. The updated meta-analysis of experimental studies showed that the drugs were not effective in reducing mortality (RR 1.1, 95%CI 1.0-1.3, I = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9-1.4, I = 0.0%), virological cure (OR 1.5, 95%CI 0.5-4.4, I = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3-5.9, I = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5-59.9, I = 76.6%). There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation. PROSPERO: CRD4202019135

The prevalence of adaptive immunity to COVID-19 and reinfection after recovery - a comprehensive systematic review and meta-analysis of 12 011 447 individuals

Research purpose: The research aims to estimate the prevalence of detectable SARS-CoV-2 antibodies, T and B memory cells after recovery, to determine the prevalence of SARS-CoV-2 reinfection, and to investigate the protective efficacy of infection with SARS-CoV-2 against reinfection. Methodology: Several online databases were searched for studies conducted between 1 January 2020 to 1 April 2021. Studies which compared COVID-19 infection between individuals with and without prior infection were included and assessed for quality and risk of bias. Pooled estimates of the prevalence of humoral and cellular immunity parameters and reinfection were obtained in a meta-analysis using bias adjusted synthesis methods. Findings: At ? 6 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG - 90.4% (95%CI 72.2-99.9, I2=89.0%, p<0.01, 5 studies), and CD4+ - 91.7% (95%CI 78.2 - 97.1, one study). The pooled prevalence of reinfection was 0.2% (95%CI 0.0 - 0.7, I2 = 98.8, 9 studies). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1 - 0.3, I2 = 90.5%, 5 studies). Research value: This review of 12 million individuals presents evidence that most individuals who recover from COVID-19 develop immunological memory to SARS-CoV-2, thus, reinfection after recovery was rare