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/)

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 conducted a living systematic review to address three questions: (1) Amongst 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 2020. We searched PubMed, Embase, bioRxiv and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 2 February 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 94 studies. Heterogeneity was high and we could not reliably estimate values for the proportion of asymptomatic infections overall (interquartile range 13-45%, prediction interval 2-89%), or in studies based on screening of defined populations (interquartile range 18-59%, prediction interval 3-95%). In screening studies at low risk of information bias, the prediction interval was 4-69% (summary proportion 23%, 95% CI 14-35%). In 40 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 18% (95% CI 14-24%, prediction interval 3-64%) and, in studies at low risk of selection bias, 25% (95% CI 18-33%, prediction interval 5-66%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.43 (95% CI 0.05-3.44, 5 studies). (3) In 11 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 in studies that were not designed to measure persistently asymptomatic infection, high risks of selection and information bias, and the absence of studies about variants of concern or in people who have been vaccinated. CONCLUSIONS This review does not provide a summary estimate of the proportion of asymptomatic SARS-CoV-2 across all study designs. In studies based on contact and outbreak investigation, most SARS-CoV-2 infections were not persistently asymptomatic. Summary estimates from meta-analysis may be misleading when variability between studies is extreme. 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 wild-type SARS-CoV-2.

Background: 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: i) symptoms and severity, ii) risk factors for severe disease, iii) the risk of becoming infected, iv) the risk of transmission and v) long-term consequences following a VOC infection. Methods: We carried out a systematic review. We searched the COVID-19 Open Access Project database up to 1 March 2022 and PubMed up to 9 May 2022 for observational epidemiological studies about alpha, beta, gamma, delta and omicron VOCs among 0 to 18 year olds. We synthesised data for each question descriptively and assessed the risks of bias at the outcome level. Results: We included 53 articles, of which 47% were from high-income countries and none were from low-income countries, according to World Bank categories. 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 at least partially vaccinated adults. Long-term symptoms or signs 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.

In acute appendicitis, timely diagnosis and rapid intervention are critical for effective management. However, geographic location and socioeconomic context can play an important role in developing countries' clinical course and outcome. The aim of this study is to observe the consequences of acute appendicitis between urban and rural patients. A prospective analytical study was conducted from April 25 to October 25, 2016, in Chittagong Medical College Hospital, Chattogram, Bangladesh. A total of 200 patients, 100 patients in each arm with a clinical diagnosis of acute appendicitis, were enrolled. 33.5% were in the age group of 21-30 years. The male:female ratio was 1.94:1. 45% of the urban patients came from the middle class, while 47% of the rural patients were from poor socioeconomic backgrounds. The mean duration of the presentation was 2.96 ± 1.88 days in urban and 5.28 ± 2.8 days in rural patients. 87% of urban and 33% of rural patients received conservative treatment before hospitalization. 74.11% of rural and 30% of urban patients delayed consenting to surgery. Perforation was found in 17.78% of urban and 33.33% of rural patients and gangrenous appendicitis in 12.22% of urban and 66.67% of rural patients. Rural patients suffered more complications like wound infection (34.4% and 68.4%, resp.), septic shock (0% and 7.9%, resp.), burst abdomen (0% and 5.3%, resp.), and death in two rural patients. Mean hospital stay was 4.37 ± 1.69 days in urban and 8.41 ± 2.44 days in rural patients. The rural population has higher morbidity and mortality when compared to the urban population of Bangladesh.