Use of Bluetooth contact tracing technology to model COVID-19 quarantine policies in high-risk closed populations.

Containment measures in high-risk closed settings, like migrant worker (MW) dormitories, are critical for mitigating emerging infectious disease outbreaks and protecting potentially vulnerable populations in outbreaks such as coronavirus disease 2019 (COVID-19). The direct impact of social distancing measures can be assessed through wearable contact tracing devices. Here, we developed an individual-based model using data collected through a Bluetooth wearable device that collected 33.6M and 52.8M contact events in two dormitories in Singapore, one apartment style and the other a barrack style, to assess the impact of measures to reduce the social contact of cases and their contacts. The simulation of highly detailed contact networks accounts for different infrastructural levels, including room, floor, block, and dormitory, and intensity in terms of being regular or transient. Via a branching process model, we then simulated outbreaks that matched the prevalence during the COVID-19 outbreak in the two dormitories and explored alternative scenarios for control. We found that strict isolation of all cases and quarantine of all contacts would lead to very low prevalence but that quarantining only regular contacts would lead to only marginally higher prevalence but substantially fewer total man-hours lost in quarantine. Reducing the density of contacts by 30% through the construction of additional dormitories was modelled to reduce the prevalence by 14 and 9% under smaller and larger outbreaks, respectively. Wearable contact tracing devices may be used not just for contact tracing efforts but also to inform alternative containment measures in high-risk closed settings.

Modelling lockdown and exit strategies for COVID-19 in Singapore.

BACKGROUND: With at least 94 countries undergoing or exiting lockdowns for contact suppression to control the COVID-19 outbreak, sustainable and public health-driven exit strategies are required. Here we explore the impact of lockdown and exit strategies in Singapore for immediate planning. METHODS: We use an agent-based model to examine the impacts of epidemic control over 480 days. A limited control baseline of case isolation and household member quarantining is used. We measure the impact of lockdown duration and start date on final infection attack sizes. We then apply a 3-month gradual exit strategy, immediately re-opening schools and easing workplace distancing measures, and compare this to long-term social distancing measures. FINDINGS: At baseline, we estimated 815 400 total infections (21.6% of the population). Early lockdown at 5 weeks with no exit strategy averted 18 500 (2.27% of baseline averted), 21 300 (2.61%) and 22 400 (2.75%) infections for 6, 8 and 9-week lockdown durations. Using the exit strategy averted a corresponding 114 700, 121 700 and 126 000 total cases, representing 12.07-13.06% of the total epidemic size under baseline. This diminishes to 9 900-11 300 for a late 8-week start time. Long-term social distancing at 6 and 8-week durations are viable but less effective. INTERPRETATION: Gradual release exit strategies are critical to maintain epidemic suppression under a new normal. We present final infection attack sizes assuming the ongoing importation of cases, which require preparation for a potential second epidemic wave due to ongoing epidemics elsewhere. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre.

Urban-Rural Disparities for COVID-19: Evidence from 10 Countries and Areas in the Western Pacific

Background Limited evidence on the effectiveness of various types of social distancing measures, from voluntary physical distancing to a community-wide quarantine, exists for the Western Pacific Region (WPR) which has large urban and rural populations. Methods We estimated the time-varying reproduction number (Rt) in a Bayesian framework using district-level mobility data provided by Facebook (i) to assess how various social distancing policies have contributed to the reduction in transmissibility of SARS-COV-2 and (ii) to examine within-country variations in behavioural responses, quantified by reductions in mobility, for urban and rural areas. Results Social distancing measures were largely effective in reducing transmissibility, with Rt estimates decreased to around the threshold of 1. Within-country analysis showed substantial variation in public compliance across regions. Reductions in mobility were significantly lower in rural and remote areas than in urban areas and metropolitan cities (p < 0.001) which had the same scale of social distancing orders in place. Conclusions Our findings provide empirical evidence that public compliance and consequent intervention effectiveness differ between urban and rural areas in the WPR. Further work is required to ascertain the factors affecting these differing behavioural responses, which can assist in policy-making efforts and increase public compliance in rural areas where populations are older and have poorer access to healthcare.

Modelling the Impact of Mass Testing to Transition from Pandemic Mitigation to Endemic COVID-19.

As countries transition from pandemic mitigation to endemic COVID-19, mass testing may blunt the impact on the healthcare system of the liminal wave. We used GeoDEMOS-R, an agent-based model of Singapore's population with demographic distributions and vaccination status. A 250-day COVID-19 Delta variant model was run at varying maximal rapid antigen test sensitivities and frequencies. Without testing, the number of infections reached 1,021,000 (899,400-1,147,000) at 250 days. When conducting fortnightly and weekly mass routine rapid antigen testing 30 days into the outbreak at a maximal test sensitivity of 0.6, this was reduced by 12.8% (11.3-14.5%) and 25.2% (22.5-28.5%). An increase in maximal test sensitivity of 0.2 results a corresponding reduction of 17.5% (15.5-20.2%) and 34.4% (30.5-39.1%). Within the maximal test sensitivity range of 0.6-0.8, test frequency has a greater impact than maximal test sensitivity with an average reduction of 2.2% in infections for each day removed between tests in comparison to a 0.43% average reduction per 1% increase in test frequency. Our findings highlight that mass testing using rapid diagnostic tests can be used as an effective intervention for countries transitioning from pandemic mitigation to endemic COVID-19.

Testing strategies to contain COVID-19 in migrant worker dormitories.

INTRODUCTION: COVID-19 transmission within overcrowded migrant worker dormitories is an ongoing global issue. Many countries have implemented extensive control measures to prevent the entire migrant worker population from becoming infected. Here, we explore case count outcomes when utilizing lockdown and testing under different testing measures and transmissibility settings. METHODS: We built a mathematical model which estimates transmission across 10 different blocks with 1000 individuals per block under different parameter combinations and testing conditions over the period of 1 month. We vary parameters including differences in block connectivity, underlying recovered proportions at the time of intervention, case importation rates and testing protocols using either PCR or rapid antigen testing. RESULTS: We estimate that a relatively transmissible environment with fortnightly PCR testing at a relatively low initial recovered proportion of 40%, low connectivity where 10% of contacts occurred outside of the infected individuals' block and a high importation rate of 1 100 000 per day, results in an average of 39 (95%Interval: 9-121) new COVID-19 cases after one month of observation. Similar results were observed for weekly rapid antigen testing at 33 (9-95) cases. INTERPRETATION: Our findings support the need for either fortnightly PCR testing or weekly rapid antigen testing in high population density environments such as migrant worker dormitories. Repeated mass testing is highly effective, preventing localized site outbreaks and reducing the need for site wide lockdowns or other extensive social distancing measures within and outside of dormitories.

Determining quarantine length and testing frequency for international border opening during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in the closure or partial closure of international borders in almost all countries. Here, we investigate the efficacy of imported case detection considering quarantine length and different testing measures for travellers on arrival. METHODS: We examine eight broad border control strategies from utilizing quarantine alone, pre-testing, entry and exit testing, and testing during quarantine. In comparing the efficacy of these strategies, we calculate the probability of detecting travellers who have been infected up to 2 weeks pre-departure according to their estimated incubation and infectious period. We estimate the number of undetected infected travellers permitted entry for these strategies across a prevalence range of 0.1-2% per million travellers. RESULTS: At 14-day quarantine, on average 2.2% (range: 0.5-8.2%) of imported infections are missed across the strategies, leading to 22 (5-82) imported cases at 0.1% prevalence per million travellers, increasing up to 430 (106-1641) at 2%. The strategy utilizing exit testing results in 3.9% (3.1-4.9%) of imported cases being missed at 7-day quarantine, down to 0.4% (0.3-0.7%) at 21-day quarantine, and the introduction of daily testing, as the most risk averse strategy, reduces the proportion further to 2.5-4.2% at day 7 and 0.1-0.2% at day 21 dependent on the tests used. Rapid antigen testing every 3 days in quarantine leads to 3% being missed at 7 days and 0.7% at 14 days, which is comparable to PCR testing with a 24-hour turnaround. CONCLUSIONS: Mandatory testing, at a minimal of pre-testing and on arrival, is strongly recommended where the length of quarantining should then be determined by the destination country's level of risk averseness, pandemic preparedness and origin of travellers. Repeated testing during quarantining should also be utilized to mitigate case importation risk and reduce the quarantining duration required.

A Systematic Review of COVID-19 Epidemiology Based on Current Evidence.

As the novel coronavirus (SARS-CoV-2) continues to spread rapidly across the globe, we aimed to identify and summarize the existing evidence on epidemiological characteristics of SARS-CoV-2 and the effectiveness of control measures to inform policymakers and leaders in formulating management guidelines, and to provide directions for future research. We conducted a systematic review of the published literature and preprints on the coronavirus disease (COVID-19) outbreak following predefined eligibility criteria. Of 317 research articles generated from our initial search on PubMed and preprint archives on 21 February 2020, 41 met our inclusion criteria and were included in the review. Current evidence suggests that it takes about 3-7 days for the epidemic to double in size. Of 21 estimates for the basic reproduction number ranging from 1.9 to 6.5, 13 were between 2.0 and 3.0. The incubation period was estimated to be 4-6 days, whereas the serial interval was estimated to be 4-8 days. Though the true case fatality risk is yet unknown, current model-based estimates ranged from 0.3% to 1.4% for outside China. There is an urgent need for rigorous research focusing on the mitigation efforts to minimize the impact on society.

Identifying COVID-19 cases in outpatient settings.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Strategies at points of entry to reduce importation risk of COVID-19 cases and reopen travel.

BACKGROUND: With more countries exiting lockdown, public health safety requires screening measures at international travel entry points that can prevent the reintroduction or importation of the severe acute respiratory syndrome-related coronavirus-2. Here, we estimate the number of cases captured, quarantining days averted and secondary cases expected to occur with screening interventions. METHODS: To estimate active case exportation risk from 153 countries with recorded coronavirus disease-2019 cases and deaths, we created a simple data-driven framework to calculate the number of infectious and upcoming infectious individuals out of 100 000 000 potential travellers from each country, and assessed six importation risk reduction strategies; Strategy 1 (S1) has no screening on entry, S2 tests all travellers and isolates test-positives where those who test negative at 7 days are permitted entry, S3 the equivalent but for a 14 day period, S4 quarantines all travellers for 7 days where all are subsequently permitted entry, S5 the equivalent for 14 days and S6 the testing of all travellers and prevention of entry for those who test positive. RESULTS: The average reduction in case importation across countries relative to S1 is 90.2% for S2, 91.7% for S3, 55.4% for S4, 91.2% for S5 and 77.2% for S6. An average of 79.6% of infected travellers are infectious upon arrival. For the top 100 exporting countries, an 88.2% average reduction in secondary cases is expected through S2 with the 7-day isolation of test-positives, increasing to 92.1% for S3 for 14-day isolation. A substantially smaller reduction of 30.0% is expected for 7-day all traveller quarantining, increasing to 84.3% for 14-day all traveller quarantining. CONCLUSIONS: The testing and isolation of test-positives should be implemented provided good testing practices are in place. If testing is not feasible, quarantining for a minimum of 14 days is recommended with strict adherence measures in place.

Effectiveness of Containment Measures Against COVID-19 in Singapore: Implications for Other National Containment Efforts.

BACKGROUND: We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number, (Equation is included in full-text article.)) over the course of the outbreak. METHODS: We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate (Equation is included in full-text article.)and evaluated increase in mean number of secondary cases per individual for each day's delay in starting isolation or quarantine. RESULTS: As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean (Equation is included in full-text article.)was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day's delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05). CONCLUSIONS: We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept (Equation is included in full-text article.)below one.

The costs of an expanded screening criteria for COVID-19: A modelling study.

OBJECTIVES: Nosocomial infection is an ongoing concern in the COVID-19 outbreak. The effective screening of suspected cases in the healthcare setting is therefore necessary, enabling the early identification and prompt isolation of cases for epidemic containment. We aimed to assess the cost and health outcomes of an extended screening strategy, implemented in Singapore on 07 February 2020, which maximizes case identification in the public healthcare system. METHODS: We explored the effects of the expanded screening criteria which allow clinicians to isolate and investigate patients presenting with undifferentiated fever or respiratory symptoms or chest x-ray abnormalities. We formulated a cost appraisal framework which evaluated the treatment costs averted from the prevention of secondary transmission in the hospital setting, as determined by a branching process infection model, and compared these to the costs of the additional testing required to meet the criteria. RESULTS: In the base case analysis, an R0 of 2.5 and incubation period of 4 days, an estimated 239 (95% CI: 201-287) cases could be averted over 150 days within the hospital setting through ESC. A corresponding $2.36 (2-2.85) million USD in costs could be averted with net cost savings of $124,000 (95% CI: -334,000 to 516,000). In the sensitivity analyses, when positive identification rates (PIR) were above 7%, regardless of R0 and incubation period, all scenarios were cost-saving. CONCLUSION: The expanded screening criteria can help to identify and promptly isolate positive COVID cases in a cost-saving manner or within acceptable cost margins where the costs incurred from the testing of negative patients could be negated by the averted costs. Outbreak control must be sustainable and effective; the proposed screening criteria should be considered to mitigate nosocomial transmission risk within healthcare facilities.

Scenarios to Manage the Demand for N95 Respirators for Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: By estimating N95 respirator demand based on simulated epidemics, we aim to assist planning efforts requiring estimations of respirator demand for the healthcare system to continue operating safely in the coming months. METHODS: We assess respiratory needs over the course of mild, moderate and severe epidemic scenarios within Singapore as a case study using a transmission dynamic model. The number of respirators required within the respiratory isolation wards and intensive care units was estimated over the course of the epidemic. We also considered single-use, extended-use and prolonged-use strategies for N95 respirators for use by healthcare workers treating suspected but negative (misclassified) or confirmed COVID-19 patients. RESULTS: Depending on the confirmed to misclassified case ratio, from 1:0 to 1:10, a range of 117.1 million to 1.1 billion masks are required for single-use. This decreases to 71.6-784.4 million for extended-use and 12.8-148.2 million for prolonged-use, representing a 31.8-38.9% and 86.5-89.1% reduction, respectively. CONCLUSION: An extended-use policy should be considered when short-term supply chains are strained but planning measures are in place to ensure long-term availability. With severe shortage expectations from a severe epidemic, as some European countries have experienced, prolonged use is necessary to prolong supply.

Importations of COVID-19 into African countries and risk of onward spread.

BACKGROUND: The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 has caused widespread transmission around the world. As new epicentres in Europe and America have arisen, of particular concern is the increased number of imported coronavirus disease 2019 (COVID-19) cases in Africa, where the impact of the pandemic could be more severe. We aim to estimate the number of COVID-19 cases imported from 12 major epicentres in Europe and America to each African country, as well as the probability of reaching 10,000 cases in total by the end of March, April, May, and June following viral introduction. METHODS: We used the reported number of cases imported from the 12 major epicentres in Europe and America to Singapore, as well as flight data, to estimate the number of imported cases in each African country. Under the assumption that Singapore has detected all the imported cases, the estimates for Africa were thus conservative. We then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until 10,000 cases are reached or the end of June, whichever is earlier. Specifically, 1,000 simulations were run separately under four different combinations of parameter values to test the sensitivity of our results. RESULTS: We estimated Morocco, Algeria, South Africa, Egypt, Tunisia, and Nigeria as having the largest number of COVID-19 cases imported from the 12 major epicentres. Based on our 1,000 simulation runs, Morocco and Algeria's estimated probability of reaching 10,000 cases by end of March was close to 100% under all scenarios. In particular, we identified countries with less than 1,000 cases in total reported by end of June whilst the estimated probability of reaching 10,000 cases by then was higher than 50% even under the most optimistic scenario. CONCLUSIONS: Our study highlights particular countries that are likely to reach (or have reached) 10,000 cases far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic.

Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study.

BACKGROUND: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. METHODS: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R0] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R0 value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. FINDINGS: For the baseline scenario, when R0 was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000-320 000), corresponding to 7·4% (IQR 6·5-8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000-776 000) when R0 was 2·0, corresponding to 19·3% (17·8-20·6) of the Singaporean population, and 1 207 000 cases (1 164 000-1 249 000) when R0 was 2·5, corresponding to 32% (30·9-33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6-99·9) when R0 was 1·5, by 93·0% (81·5-99·7) when R0 was 2·0, and by 78·2% (59·0 -94·4) when R0 was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R0 of 1·5. INTERPRETATION: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre.