Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

Role of mammography accessibility, deprivation and spatial effect in breast cancer screening participation in France: an observational ecological study.

BACKGROUND: The detection of cancer in its early latent stages can improve patients' chances of recovery and thereby reduce the overall burden of the disease. Our objectives were to investigate factors (geographic accessibility and deprivation level) affecting mammography screening participation variation and to determine how much geographic variation in participation rates can be explained by spillover effects between adjacent areas, while controlling for covariates. METHODS: Mammography screening participation rates between 2015 and 2016 were calculated by census blocks (CB), for women aged 50-74 years, residing in Lyon metropolitan area. Global spatial autocorrelation tests were applied to identify the geographic variation of participation. Spatial regression models were used to incorporate spatial structure to estimate associations between mammography participation rate and the combined effect (geographic accessibility and deprivation level) adjusting for modes of travel and social cohesion. RESULTS: The mammography participation rate was found to have a statistically significant and positive spatial correlation. The participation rate of one CB was significantly and positively associated with the participation rates of neighbouring CB. The participation was 53.2% in residential and rural areas and 46.6% in urban areas, p < 0.001. Using Spatial Lag models, whereas the population living in most deprived CBs have statistically significantly lower mammography participation rates than lower deprived ones, significant interaction demonstrates that the relation differs according to the degree of urbanization. CONCLUSIONS: This study makes an important methodological contribution in measuring geographical access and understanding better the combined effect of deprivation and the degree of urbanization on mammography participation and other contextual factors that affect the decision of using mammography screening services -which is a critical component of healthcare planning and equity.

Outbreaks of publications about emerging infectious diseases: the case of SARS-CoV-2 and Zika virus.

BACKGROUND: Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections to analyse the evolution of the evidence. METHODS: We annotated publications on Zika virus and SARS-CoV-2 that we collected using living evidence databases according to study design. We used descriptive statistics to categorise and compare study designs over time. RESULTS: We found 2286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294 (24%). For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. The number of preprints was much higher for SARS-CoV-2 than for Zika virus. CONCLUSIONS: Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.

SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review.

OBJECTIVES: Infections by SARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently than earlier viral lineages. We aimed to address five questions about SARS-CoV-2 VOC infections in children and adolescents: (1) symptoms and severity, (2) risk factors for severe disease, (3) the risk of infection, (4) the risk of transmission and (5) long-term consequences following a VOC infection. DESIGN: Systematic review. DATA SOURCES: The COVID-19 Open Access Project database was searched up to 1 March 2022 and PubMed was searched up to 9 May 2022. ELIGIBILITY CRITERIA: We included observational studies about Alpha, Beta, Gamma, Delta and Omicron VOCs among ≤18-year-olds. We included studies in English, German, French, Greek, Italian, Spanish and Turkish. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted and verified the data and assessed the risk of bias. We descriptively synthesised the data and assessed the risks of bias at the outcome level. RESULTS: We included 53 articles. Most children with any VOC infection presented with mild disease, with more severe disease being described with the Delta or the Gamma VOC. Diabetes and obesity were reported as risk factors for severe disease during the whole pandemic period. The risk of becoming infected with a SARS-CoV-2 VOC seemed to increase with age, while in daycare settings the risk of onward transmission of VOCs was higher for younger than older children or partially vaccinated adults. Long-term symptoms following an infection with a VOC were described in <5% of children and adolescents. CONCLUSION: Overall patterns of SARS-CoV-2 VOC infections in children and adolescents are similar to those of earlier lineages. Comparisons between different pandemic periods, countries and age groups should be improved with complete reporting of relevant contextual factors, including VOCs, vaccination status of study participants and the risk of exposure of the population to SARS-CoV-2. PROSPERO REGISTRATION NUMBER: CRD42022295207.