Background India has experienced the second largest outbreak of COVID-19 globally, yet there is a paucity of studies analysing contact tracing data in the region which can optimise public health interventions (PHI’s). Methods We analysed contact tracing data from Karnataka, India between 9 March and 21 July 2020. We estimated metrics of transmission including the reproduction number (R), overdispersion (k), secondary attack rate (SAR), and serial interval. R and k were jointly estimated using a Bayesian Markov Chain Monte Carlo approach. We studied determinants of risk of further transmission and risk of being symptomatic using Poisson regression models. Findings Up to 21 July 2020, we found 111 index cases that crossed the super-spreading threshold of ≥8 secondary cases. Among 956 confirmed traced cases, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases. Among 16715 contacts, overall SAR was 3.6% [95% CI, 3.4–3.9] and symptomatic cases were more infectious than asymptomatic cases (SAR 7.7% vs 2.0%; aRR 3.63 [3.04–4.34]). As compared to infectors aged 19–44 years, children were less infectious (aRR 0.21 [0.07–0.66] for 0–5 years and 0.47 [0.32–0.68] for 6–18 years). Infectors who were confirmed ≥4 days after symptom onset were associated with higher infectiousness (aRR 3.01 [2.11–4.31]). As compared to asymptomatic cases, symptomatic cases were 8.16 [3.29–20.24] times more likely to cause symptomatic infection in their secondary cases. Serial interval had a mean of 5.4 [4.4–6.4] days, and case fatality rate was 2.5% [2.4–2.7] which increased with age. Conclusion We found significant heterogeneity in the individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in the underlying number of contacts. To strengthen contact tracing in over-dispersed outbreaks, testing and tracing delays should be minimised and retrospective contact tracing should be implemented. Targeted measures to reduce potential superspreading events should be implemented. Interventions aimed at children might have a relatively small impact on reducing transmission owing to their low symptomaticity and infectivity. We propose that symptomatic cases could cause a snowballing effect on clinical severity and infectiousness across transmission generations; further studies are needed to confirm this finding.

Case fatality rate (CFR) and doubling time are important characteristics of any epidemic. For coronavirus disease 2019 (COVID-19), wide variations in the CFR and doubling time have been noted among various countries. Early in the epidemic, CFR calculations involving all patients as denominator do not account for the hospitalised patients who are ill and will die in the future. Hence, we calculated cumulative CFR (cCFR) using only patients whose final clinical outcomes were known at a certain time point. We also estimated the daily average doubling time. Calculating CFR using this method leads to temporal stability in the fatality rates, the cCFR stabilises at different values for different countries. The possible reasons for this are an improved outcome rate by the end of the epidemic and a wider testing strategy. The United States, France, Turkey and China had high cCFR at the start due to low outcome rate. By 22 April, Germany, China and South Korea had a low cCFR. China and South Korea controlled the epidemic and achieved high doubling times. The doubling time in Russia did not cross 10 days during the study period.

Background and ObjectivesThe involvement of medical students in strategies to control COVID-19 might be considered to cope with the shortage of healthcare workers. This study aims at assessing the level of knowledge about COVID-19, willingness to volunteer, potential areas of involvement and reasons for deterrence towards volunteering among medical students.MethodsA cross-sectional study was conducted among undergraduate medical students of a tertiary care teaching hospital in New Delhi. A web-based questionnaire was used to elicit demographic information, knowledge of COVID-19, willingness to volunteer and reasons for deterrence for working during COVID-19 pandemic and self-declared knowledge in six domains.ResultsA total of 292 students participated in the study with a mean age of 19.9±3.1 years. The mean (S.D.) knowledge score of COVID-19 was 6.9 (1.1) (maximum score 10). Knowledge score was significantly different among preclinical (6.5), paraclinical (7.18), and clinical groups (7.03). Almost three fourth (75.3%) participants were willing to volunteer in COVID-19 pandemic, though 67.8% had not received any training in emergency medicine or public health crisis management. Willingness to work was maximum in areas of social work and indirect patient care (62.3% each). Lack of personal protective equipment was cited as a highly deterrent factor for volunteering (62.7%) followed by fear of transmitting the infection to family (45.9%), fear of causing harm to the patient (34.2%), and absence of treatment (22.2%).Interpretation & conclusionsMajority of the students were willing to volunteer even though they had not received adequate training. Students may serve as an auxiliary force during the pandemic, especially in the non-clinical setting.

Background Bariatric surgery can alleviate cardiovascular risk via effects on cardiovascular disease (CVD) risk factors such as diabetes mellitus, hypertension, and dyslipidemia. Our study aimed to assess the cholesterol efflux capacity (CEC) of HDL as a negative risk factor for CVD in individuals with obesity and identify the factors associated with improvement in CEC 3 months following bariatric surgery. Methods We recruited 40 control individuals (mean BMI of 22.2 kg/m2) and 56 obese individuals (mean BMI of 45.9 kg/m2). The biochemical parameters, inflammatory status and CEC of HDL was measured for the obese individuals before bariatric surgery and at 3 months after surgery. The CEC was measured using a cell-based cholesterol efflux system of BODIPY-cholesterol-labelled THP-1 macrophages. Results A significant reduction in BMI (− 17%, p < 0.001), resolution of insulin sensitivity (HOMA2-IR = − 23.4%, p = 0.002; Adipo IR = − 16%, p = 0.009) and inflammation [log resistin = − 6%, p = 0.07] were observed 3 months post-surgery. CEC significantly improved 3 months after surgery [Pre: 0.91 ± 0.13; Post: 1.02 ± 0.16; p = 0.001] despite a decrease in HDL-C levels. The change in CEC correlated with the change in apo A-I (r = 0.39, p = 0.02) and adiponectin levels (r = 0.35, p = 0.03). Conclusion The results suggest that improvements in CEC, through improvement in adipose tissue health in terms of adipokine secretion and insulin sensitivity could be an important pathway in modulating obesity-related CVD risk.

Background: Aprepitant has been shown to reduce chemotherapy-induced nausea and vomiting in children receiving highly emetogenic chemotherapy (HEC). In this study, we assessed the cost-effectiveness of aprepitant for children receiving HEC in India, United Kingdom, and the United States. Procedure:We utilized individual patient-level outcome data from a pediatric randomized trial, which demonstrated the superiority of an aprepitant-based anti-emetic prophylaxis over standard ondansetron and dexamethasone for HEC. Health state for each day of follow-up was analyzed and quality-adjusted life years (QALYs) were estimated. The incremental cost-utility ratio (ICUR), incremental cost-effectiveness ratio (ICER), and net monetary benefit (NMB) for each country were estimated. Sensitivity analyses by varying cost of aprepitant, hospitalization, and health state utility values by ±25% were conducted.Results: Use of the aprepitant-based regimen resulted in gain of 0.

IntroductionDue to the accelerated pace and quantum of scientific publication during the COVID-19 pandemic, a large number of articles on COVID-19 have been retracted. Pre-prints though not peer-reviewed offer the advantage of rapid dissemination of new findings. In this study, we aim to systematically compare the article characteristics, time to retraction, social media attention, citations, and reasons for retraction between retracted pre-print and peer-reviewed articles on COVID-19. MethodsWe utilized the Retraction Watch database to identify retracted articles on COVID-19 published from 1st January 2020 to 10th March 2022. The articles were reviewed and metadata such as article characteristics (type, category), time to retraction, reasons for retraction, and Altmetric Attention Score (AAS) and citation count were collected. ResultsWe identified 40 retracted pre-prints and 143 retracted peer-reviewed articles. The median (IQR) retraction time for pre-print and peer-reviewed articles was 29 (10-81.5) days and 139 (63-202) days (p = 0.0001). Pre-prints and peer-reviewed article had median (IQR) AAS of 26.5 (4-1155) and 8 (1-38.5), respectively (p = 0.0082). The median (IQR) citation count for pre-prints and peer-reviewed articles was 3 (0-14) and 3 (0-17), respectively (p = 0.5633). The AAS and citation counts were correlated for both pre-prints (r = 0.5200, p = 0.0006) and peer-reviewed articles(r = 0.5909, p = 0.0001). The commonest reason for retraction for pre-prints and peer-reviewed articles concerns about data and results.ConclusionThe increased adoption of pre-prints results in faster identification of erroneous articles compared to the traditional peer-review process.

Brief AbstractWe analysed SARS-CoV-2 surveillance and contact tracing data from Karnataka, India up to 21 July 2020. We estimated metrics of infectiousness and the tendency for superspreading (overdispersion), and evaluated potential determinants of infectiousness and symptomaticity in COVID-19 cases. Among 956 cases confirmed to be forward-traced, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases, suggesting significant heterogeneity in individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in underlying number of contacts. Secondary attack rate was 3.6% among 16715 close contacts. Transmission was higher when index case was aged >18 years, or was symptomatic (adjusted risk ratio, aRR 3.63), or was lab-confirmed ≥4 days after symptom onset (aRR 3.01). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 times more likely to generate symptomatic secondaries. This could potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are suggested to confirm this. Mean serial interval was 5.4 days. Adding backward contact tracing and targeting control measures to curb super-spreading may be prudent. Due to low symptomaticity and infectivity, interventions aimed at children might have a relatively small impact on reducing transmission.Structured AbstractBackgroundIndia has experienced the second largest outbreak of COVID-19 globally, yet there is a paucity of studies analysing contact tracing data in the region. Such studies can elucidate essential transmission metrics which can help optimize disease control policies.MethodsWe analysed contact tracing data collected under the Integrated Disease Surveillance Programme from Karnataka, India between 9 March and 21 July 2020. We estimated metrics of disease transmission including the reproduction number (R), overdispersion (k), secondary attack rate (SAR), and serial interval. R and k were jointly estimated using a Bayesian Markov Chain Monte Carlo approach. We evaluated the effect of age and other factors on the risk of transmitting the infection, probability of asymptomatic infection, and mortality due to COVID-19.FindingsUp to 21 July, we found 111 index cases that crossed the super-spreading threshold of ≥8 secondary cases. R and k were most reliably estimated at R 0.75 (95% CI, 0.62-0.91) and k 0.12 (0.11-0.15) for confirmed traced cases (n=956); and R 0.91 (0.72-1.15) and k 0.22 (0.17-0.27) from the three largest clusters (n=394). Among 956 confirmed traced cases, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases. Among 16715 contacts, overall SAR was 3.6% (3.4-3.9) and symptomatic cases were more infectious than asymptomatic cases (SAR 7.7% vs 2.0%; aRR 3.63 [3.04-4.34]). As compared to infectors aged 19-44 years, children were less infectious (aRR 0.21 [0.07-0.66] for 0-5 years and 0.47 [0.32-0.68] for 6-18 years). Infectors who were confirmed ≥4 days after symptom onset were associated with higher infectiousness (aRR 3.01 [2.11-4.31]). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 (3.29-20.24) times more likely to generate symptomatic secondaries. Serial interval had a mean of 5.4 (4.4-6.4) days with a Weibull distribution. Overall case fatality rate was 2.5% (2.4-2.7) which increased with age.ConclusionWe found significant heterogeneity in the individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in the underlying number of contacts. To strengthen contact tracing in over-dispersed outbreaks, testing and tracing delays should be minimised, retrospective contact tracing should be considered, and contact tracing performance metrics should be utilised. Targeted measures to reduce potential superspreading events should be implemented. Interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission owing to their low symptomaticity and infectivity. There is some evidence that symptomatic cases produce secondary cases that are more likely to be symptomatic themselves which may potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are needed to confirm this finding.FundingGiridhara R Babu is funded by an Intermediate Fellowship by the Wellcome Trust DBT India Alliance (Clinical and Public Health Research Fellowship); grant number: IA/CPHI/14/1/501499.

ObjectivesTo assess the cost-effectiveness of addition of olanzapine to a prophylactic antiemetic regimen containing aprepitant, dexamethasone and ondansetron among children receiving highly emetogenic chemotherapy (HEC) in India, Bangladesh, Indonesia, the UK and the USA.MethodsHealth states were estimated using individual patient-level outcome data from a randomised trial. The incremental cost–utility ratio (ICUR), incremental cost-effectiveness ratio and net monetary benefit (NMB) were calculated from the patient perspective for India, Bangladesh, Indonesia, the UK and the USA. One-way sensitivity analysis was done by varying the cost of olanzapine, cost of hospitalisation and utility values by ±25%.ResultsThe olanzapine arm had an increment of 0.0018 quality-adjusted life-years (QALY) over the control arm. The mean total expenditure in the olanzapine arm was greater by US$0.51, US$0.43, US$6.73, US$11.05 and US$12.35 in India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR($/QALY) was US$282.60 in India, US$241.42 in Bangladesh, US$3755.93 in Indonesia, US$6161.83 in the UK and US$6887.41 in the USA. The NMB was US$9.86, US$10.12, US$14.08, US$44.74 and US$98.79 for India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR estimates of the base case and sensitivity analysis were below the willingness-to-pay threshold in all scenarios.ConclusionThe addition of olanzapine as a fourth agent for antiemetic prophylaxis is cost-effective despite an increase in overall expenditure. Olanzapine should be uniformly considered for children receiving HEC.