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 2 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 2 = 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 2 = 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 2 = 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.Registration PROSPERO: CRD42020201234

Aims:The effectiveness of physical activity (PA) programs for prevention of gestational diabetes (GDM) lacks conclusive evidence. The aim of this study was to generate clear evidence regarding the effectiveness of physical activity programs in GDM prevention to guide clinical practice. Methods: PubMed/Medline, ISI Web of Science, Scopus, and EMBASE were searched to identify the randomized trials (RCTs) published until June 2019. Randomised controlled trials enrolling women at high risk before the 20 th week of gestation comparing the effect of PA interventions with usual care for prevention of GDM were retrieved. Data obtained were synthesised using a bias-adjusted model of meta-analysis. Results: A total of 1467 adult women in 11 eligible trials were included. The risk of GDM was significantly lower with PA, but only when it was delivered in the healthcare facility (RR 0.53; 95% CI 0.38 to 0.74). The number needed to treat with PA in pregnancy (compared to usual care) to prevent one GDM event was 18 (95% CI 14 -29). The overall effect of PA interventions regardless of location of the intervention was RR 0.69 (95% CI 0.51 -0.94). Conclusions: This study provides evidence that in-facility physical activity programs started before the 20 th week of gestation can significantly decrease the incidence of GDM among women at high risk.

Objective 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. Methods 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. Results 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 2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9–1.4, I 2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5–4.4, I 2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3–5.9, I 2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5–59.9, I 2 = 76.6%). Conclusion There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation. Registration PROSPERO: CRD42020191353.

Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome-incident GDM in women at high risk.We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85-1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed.

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Backgrounds Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. Methods We conducted a survey of systematic reviews published in two periods: January 1, 2015, to January 1, 2020, and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. Results We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant (proportion difference=−0.09, 95% CI −0.21 to 0.03, p = 0.12). Conclusion Systematic review authors routinely treated studies with zero-events in both arms as “non-informative” carriers and excluded them from their reviews. Whether studies with no events are “informative” or not largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

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Objectives This study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies as well as T and B memory cells during infection with SARS-CoV-2 and after recovery. In addition, prevalence of COVID-19 reinfection, and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. Methods and analyses A synthesis of existing research was conducted. The Cochrane Library for COVID-19 resources, the China Academic Journals Full Text Database, PubMed, and Scopus as well as preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. We included studies with the relevant outcomes of interest. All 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 between included studies was assessed using the I2 and Cochrans Q statistics and publication bias was assessed using Doi plots. Results Fifty-four studies, from 18 countries, with a total of 12 011 447 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 to 99.9, I2=89.0%, 5 studies), CD4+ 91.7% (95%CI 78.2 to 97.1, one study), and memory B cells 80.6% (95%CI 65.0 to 90.2, one study) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0 to 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 to 0.3, I2 = 90.5%, 5 studies). Conclusion Around 90% of people previously infected with SARS-CoV-2 had evidence of immunological memory to SARS-CoV-2, which was sustained for at least 6-8 months after recovery, and had a low risk of reinfection.