Objectives: To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity. Methods: A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020. Results: We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus. Conclusion: There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.

Summary In this review, we systematically searched and summarized the evidence on the immune response and reinfection rate following SARS‐CoV‐2 infection. We also retrieved studies on SARS‐CoV and MERS‐CoV to assess the long‐term duration of antibody responses. A protocol based on Cochrane rapid review methodology was adhered to and databases were searched from 1/1/2000 until 26/5/2020. Of 4744 citations retrieved, 102 studies met our inclusion criteria. Seventy‐four studies were retrieved on SARS‐CoV‐2. While the rate and timing of IgM and IgG seroconversion were inconsistent across studies, most seroconverted for IgG within 2 weeks and 100% (N = 62) within 4 weeks. IgG was still detected at the end of follow‐up (49‐65 days) in all patients (N = 24). Neutralizing antibodies were detected in 92%‐100% of patients (up to 53 days). It is not clear if reinfection with SARS‐CoV‐2 is possible, with studies more suggestive of intermittent detection of residual RNA. Twenty‐five studies were retrieved on SARS‐CoV. In general, SARS‐CoV‐specific IgG was maintained for 1‐2 years post‐infection and declined thereafter, although one study detected IgG up to 12 years post‐infection. Neutralizing antibodies were detected up to 17 years in another study. Three studies on MERS‐CoV reported that IgG may be detected up to 2 years. In conclusion, limited early data suggest that most patients seroconvert for SARS‐CoV‐2‐specific IgG within 2 weeks. While the long‐term duration of antibody responses is unknown, evidence from SARS‐CoV studies suggest SARS‐CoV‐specific IgG is sustained for 1‐2 years and declines thereafter.

ObjectiveTo synthesise evidence from exclusively primary prevention data on the effectiveness of statins for prevention of cardiovascular disease (CVD), including stroke, and outcomes stratified by baseline risk and gender.DesignOverview of systematic reviews (SRs) using Revised-AMSTAR approach to assess quality.Data sourcesCochrane Database of Systematic Reviews, MEDLINE, Embase, PubMed, Scopus and PROSPERO to June 2017.Eligibility criteria for selecting studiesSRs of randomised control trials (RCTs) or individual patient data (IPD) from RCTs, examining the effectiveness of statins versus placebo or no treatment on all-cause mortality, coronary heart disease, CVD (including stroke) and composite endpoints, with stratification by baseline risk and gender.Data extraction and synthesisTwo independent reviewers extracted data and assessed methodological quality. A narrative synthesis was conducted.ResultsThree SRs were included. Quality of included SRs was mixed, and none reported on the risk of bias of included trials.We found trends towards reduced all-cause mortality in all SRs (RR 0.91 [95% CI 0.85 to 0.97]), (RR 0.91 [95% CI 0.83 to 1.01]) and (RR 0.78 [95% CI 0.53 to 1.15]) though it was not statistically significant in two SRs. When stratified by baseline risk, the effect on all-cause mortality was no longer statistically significant except in one medium risk category. One review reported significant reductions (RR 0.85 [95% CI 0.77 to 0.95]) in vascular deaths and non-significant reductions in non-vascular deaths (RR 0.97 [95% CI 0.88 to 1.07]). There were significant reductions in composite outcomes overall, but mixed results were reported in these when stratified by baseline risk. These reviews included studies with participants considered risk equivalent to those with established CVD.ConclusionsThere is limited evidence on the effectiveness of statins for primary prevention with mixed findings from studies including participants with widely ranging baseline risks. Decision making for the use of statins should consider individual baseline risk, absolute risk reduction and whether risk reduction justifies potential harms and taking a daily medicine for life.Trial registration numberCRD42017064761.

IMPORTANCEThe association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.OBJECTIVE To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.DATA SOURCES PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.STUDY SELECTION Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.DATA EXTRACTION AND SYNTHESIS Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken. MAIN OUTCOMES AND MEASURESPrimary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.FINDINGS Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive. CONCLUSIONS AND RELEVANCEThe results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

The Community Mothers programme had sustained beneficial effects on parenting skills and maternal self-esteem 7 years later with benefit extending to subsequent children.