Early evidence of effectiveness of digital contact tracing for SARS-CoV-2 in Switzerland.

In the wake of the pandemic of coronavirus disease 2019 (COVID-19), contact tracing has become a key element of strategies to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given the rapid and intense spread of SARS-CoV-2, digital contact tracing has emerged as a potential complementary tool to support containment and mitigation efforts. Early modelling studies highlighted the potential of digital contact tracing to break transmission chains, and Google and Apple subsequently developed the Exposure Notification (EN) framework, making it available to the vast majority of smartphones. A growing number of governments have launched or announced EN-based contact tracing apps, but their effectiveness remains unknown. Here, we report early findings of the digital contact tracing app deployment in Switzerland. We demonstrate proof-of-principle that digital contact tracing reaches exposed contacts, who then test positive for SARS-CoV-2. This indicates that digital contact tracing is an effective complementary tool for controlling the spread of SARS-CoV-2. Continued technical improvement and international compatibility can further increase the efficacy, particularly also across country borders.

[The preparedness of the Italian obstetric surveillance system in the response to the emergency of the SARS-CoV-2 pandemic: methodological aspects of a population-based study]. / La preparedness dell'Italian obstetric surveillance system in occasione della pandemia da SARS-CoV-2: aspetti metodologici di uno studio di popolazione.

This paper aims to describe the Italian obstetric surveillance system (ItOSS) preparedness as an element for a timely response to the new Coronavirus pandemic. ItOSS is a surveillance network that has been collecting data on maternal mortality and conducting population studies on obstetric near misses since 2013. At the beginning of the pandemic, ItOSS launched a new population-based project to monitor SARS-CoV-2 infection during pregnancy and post-partum and promptly give back information useful to clinicians and decision-makers. All the regions and autonomous provinces, for a total of 289 birth units (PN), joined the study. Data relating to pregnant or post-partum women with a confirmed SARS-CoV-2 infection diagnosis addressing the maternities for outpatient visits or hospitalization were collected. The project methodology entails that each participating maternity reports the cases to ItOSS uploading data through an open-source platform. The on-line form includes sociodemographic and clinical data and maternal-neonatal outcomes. Biological samples to detect possible vertical transmission are also collected voluntarily. A total of 534 incident cases were reported from February 25th to July 10th 2020; 7 regions also collected biological samples for 227 cases; data collection is still ongoing.A preliminary analysis of the first 146 SARS-CoV-2 positive women who gave birth between February 25th to April 22nd shows an incidence rate of the infection equal to 2.1/1,000 in Italy and 6.9/1,000 in the Lombardy Region (Northern Italy). The brief time needed to setting up and operating the project, the national coverage, the adoption of shared tools for data collection, the quality and completeness of the information collected show how the availability of active networks like ItOSS represents a crucial element to hold a high level of preparedness in case of a health emergency.

Quantifying SARS-CoV-2 Infection Risk Within the Google/Apple Exposure Notification Framework to Inform Quarantine Recommendations.

Most early Bluetooth-based exposure notification apps use three binary classifications to recommend quarantine following SARS-CoV-2 exposure: a window of infectiousness in the transmitter, ≥15 minutes duration, and Bluetooth attenuation below a threshold. However, Bluetooth attenuation is not a reliable measure of distance, and infection risk is not a binary function of distance, nor duration, nor timing. We model uncertainty in the shape and orientation of an exhaled virus-containing plume and in inhalation parameters, and measure uncertainty in distance as a function of Bluetooth attenuation. We calculate expected dose by combining this with estimated infectiousness based on timing relative to symptom onset. We calibrate an exponential dose-response curve based on infection probabilities of household contacts. The probability of current or future infectiousness, conditioned on how long postexposure an exposed individual has been symptom-free, decreases during quarantine, with shape determined by incubation periods, proportion of asymptomatic cases, and asymptomatic shedding durations. It can be adjusted for negative test results using Bayes' theorem. We capture a 10-fold range of risk using six infectiousness values, 11-fold range using three Bluetooth attenuation bins, ∼sixfold range from exposure duration given the 30 minute duration cap imposed by the Google/Apple v1.1, and ∼11-fold between the beginning and end of 14 day quarantine. Public health authorities can either set a threshold on initial infection risk to determine 14-day quarantine onset, or on the conditional probability of current and future infectiousness conditions to determine both quarantine and duration.

Individual-Level Evaluation of the Exposure Notification Cascade in the SwissCovid Digital Proximity Tracing App: Observational Study.

BACKGROUND: Digital proximity tracing (DPT) aims to complement manual contact tracing (MCT) in identifying exposed contacts and preventing further transmission of SARS-CoV-2 in the population. Although several DPT apps, including SwissCovid, have shown to have promising effects on mitigating the pandemic, several challenges have impeded them from fully achieving the desired results. A key question now relates to how the effectiveness of DPT can be improved, which requires a better understanding of factors influencing its processes. OBJECTIVE: In this study, we aim to provide a detailed examination of the exposure notification (EN) cascade and to evaluate potential contextual influences for successful receipt of an EN and subsequent actions taken by cases and contacts in different exposure settings. METHODS: We used data from 285 pairs of SARS-CoV-2-infected cases and their contacts within an observational cohort study of cases and contacts identified by MCT and enrolled between August 6, 2020, and January 17, 2021, in the canton of Zurich, Switzerland. We surveyed participants with electronic questionnaires. Data were summarized descriptively and stratified by exposure setting. RESULTS: We found that only 79 (58.5%) of 135 contacts using the SwissCovid app whose corresponding cases reported to have triggered the EN also received one. Of these, 18 (22.8%) received the EN before MCT. Compared to those receiving an EN after MCT (61/79, 77.2%), we observed that a higher proportion of contacts receiving an EN before MCT were exposed in nonhousehold settings (11/18, 61.1%, vs 34/61, 55.7%) and their corresponding cases had more frequently reported mild-to-moderate symptoms (14/18, 77.8%, vs 42/61, 68.9%). Of the 18 contacts receiving an EN before MCT, 14 (77.8%) took recommended measures: 12 (66.7%) were tested for SARS-CoV-2, and 7 (38.9%) called the SwissCovid Infoline. In nonhousehold settings, the proportion of contacts taking preventive actions after receiving an EN was higher compared to same-household settings (82%, vs 67%). In addition, 1 (9%) of 11 ENs received in the nonhousehold setting before MCT led to the identification of a SARS-CoV-2-infected case by prompting the contact to get tested. This corresponds to 1 in 85 exposures of a contact to a case in a nonhousehold setting, in which both were app users and the case triggered the EN. CONCLUSIONS: Our descriptive evaluation of the DPT notification cascade provides further evidence that DPT is an important complementary tool in pandemic mitigation, especially in nonhousehold exposure settings. However, the effect of DPT apps can only be exerted if code generation processes are efficient and exposed contacts are willing to undertake preventive actions. This highlights the need to focus efforts on keeping barriers to efficient code generation as low as possible and promoting not only app adoption but also compliance with the recommended measures upon an EN. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry 14990068; https://doi.org/10.1186/ISRCTN14990068.

Automated Digital Notification of COVID-19 Diagnoses Through Text and Email Messaging - North Carolina, December 2020-January 2021.

During October 3, 2020-January 9, 2021, North Carolina experienced a 400% increase in daily reported COVID-19 cases (1). To handle the increased number of cases and rapidly notify persons receiving a positive SARS-CoV-2 test result (patients), North Carolina state and local health departments moved from telephone call notification only to telephone call plus automated text and email notification (digital notification) beginning on December 24, 2020. Overall, among 200,258 patients, 142,975 (71%) were notified by telephone call or digital notification within the actionable period (10 days from their diagnosis date)* during January 2021, including at least 112,543 (56%) notified within 24 hours of report to North Carolina state and local health departments, a significantly higher proportion than the 25,905 of 175,979 (15%) notified within 24 hours during the preceding month (p<0.001). Differences in text notification by age, race, and ethnicity were observed. Automated digital notification is a feasible, rapid and efficient method to support timely outreach to patients, provide guidance on how to isolate, access resources, inform close contacts, and increase the efficiency of case investigation staff members.

Myocarditis and Pericarditis After COVID-19 mRNA Vaccination: Practical Considerations for Care Providers.

The mRNA vaccines against COVID-19 infection have been effective in reducing the number of symptomatic cases worldwide. With widespread uptake, case series of vaccine-related myocarditis/pericarditis have been reported, particularly in adolescents and young adults. Men tend to be affected with greater frequency, and symptom onset is usually within 1 week after vaccination. Clinical course appears to be mild in most cases. On the basis of the available evidence, we highlight a clinical framework to guide providers on how to assess, investigate, diagnose, and report suspected and confirmed cases. In any patient with highly suggestive symptoms temporally related to COVID-19 mRNA vaccination, standardized workup includes serum troponin measurement and polymerase chain reaction testing for COVID-19 infection, routine additional lab work, and a 12-lead electrocardiogram. Echocardiography is recommended as the imaging modality of choice for patients with unexplained troponin elevation and/or pathologic electrocardiogram changes. Cardiovascular specialist consultation and hospitalization should be considered on the basis of the results of standard investigations. Treatment is largely supportive, and myocarditis/pericarditis that is diagnosed according to defined clinical criteria should be reported to public health authorities in every jurisdiction. Finally, we recommend COVID-19 vaccination in all individuals in accordance with the Health Canada and National Advisory Committee on Immunization guidelines. In patients with suspected myocarditis/pericarditis after the first dose of an mRNA vaccine, deferral of a second dose is recommended until additional reports become available.

A Data-Driven Simulation of the Exposure Notification Cascade for Digital Contact Tracing of SARS-CoV-2 in Zurich, Switzerland.

Importance: Digital contact tracing (DCT) apps have been released in several countries to help interrupt SARS-CoV-2 transmission chains. However, the effect of DCT on pandemic mitigation remains to be demonstrated. Objective: To estimate key populations and performance indicators along the exposure notification cascade of the SwissCovid DCT app in a clearly defined regional and temporal context. Design, Setting, and Participants: This comparative effectiveness study was based on a simulation informed by measured data from issued quarantine recommendations and positive SARS-CoV-2 test results after DCT exposure notifications in the canton of Zurich. A stochastic model was developed to re-create the DCT notification cascade for Zurich. Population sizes at each cascade step were estimated using triangulation based on publicly available administrative and observational research data for the study duration from September 1 to October 31, 2020. The resultant estimates were checked for internal consistency and consistency with upstream or downstream estimates in the cascade. Stochastic sampling from data-informed parameter distributions was performed to explore the robustness of results. Subsequently, key performance indicators were evaluated to assess the potential contribution of DCT compared with manual contact tracing. Main Outcomes and Measures: Receiving a voluntary quarantine recommendation and/or a positive SARS-CoV-2 test result after exposure notification. Results: In September 2020, 537 app users received a positive SARS-CoV-2 test result in Zurich, 324 of whom received and entered an upload authorization code. This code triggered an app notification for an estimated 1374 (95% simulation interval [SI], 932-2586) proximity contacts and led to 722 information hotline calls, with an estimated 170 callers (95% SI, 154-186) receiving a quarantine recommendation. An estimated 939 (95% SI, 720-1127) notified app users underwent testing for SARS-CoV-2, of whom 30 (95% SI, 23-36) had positive results after an app notification. Key indicator evaluations revealed that the DCT app triggered quarantine recommendations for the equivalent of 5% of all exposed contacts placed in quarantine by manual contact tracing. For every 10.9 (95% SI, 7.6-15.6) upload authorization codes entered in the app, 1 contact had positive test results for SARS-CoV-2 after app notification. Longitudinal indicator analyses demonstrated bottlenecks in the notification cascade, because capacity limits were reached owing to an increased incidence of SARS-CoV-2 infection in October 2020. Conclusions and Relevance: In this simulation study of the notification cascade of the SwissCovid DCT app, receipt of exposure notifications was associated with quarantine recommendations and identification of SARS-CoV-2-positive cases. These findings in notified proximity contacts reflect important intermediary steps toward transmission prevention.

The Impact of COVID-19 Containment Actions on Extra-Analytical Phases of the Clinical Laboratory: A Case Report.

Laboratory information systems need to adapt to new demands created by the COVID-19 pandemic, which has set up new normals like containment measures and social distancing. Some of these have negatively impacted the pre- and postanalytical phases of laboratory testing. Here, we present an intriguing finding related to the generation of the accession number/specimen number on the investigation module of a hospital management information system and its impact on the dissemination of reports resulting in the wrong release of reports on a female patient amidst the background of COVID-19 containment measures. We analyze the situation that led to this false reporting and the importance of the proper customization of information software in laboratories along with a robust postanalytical framework of laboratory work culture to avert such untoward incidents. This introspection has made us realize that COVID-19 has been a scientific, medical, and social challenge. We need to redefine our priorities in the days to come because SARS-CoV-2 is here to stay.

Estimating the COVID-19 Prevalence in Spain With Indirect Reporting via Open Surveys.

During the initial phases of the COVID-19 pandemic, accurate tracking has proven unfeasible. Initial estimation methods pointed toward case numbers that were much higher than officially reported. In the CoronaSurveys project, we have been addressing this issue using open online surveys with indirect reporting. We compare our estimates with the results of a serology study for Spain, obtaining high correlations (R squared 0.89). In our view, these results strongly support the idea of using open surveys with indirect reporting as a method to broadly sense the progress of a pandemic.

Identifying the outbreak signal of COVID-19 before the response of the traditional disease monitoring system.

SYNOPSIS: Early identification of the emergence of an outbreak of a novel infectious disease is critical to generating a timely response. The traditional monitoring system is adequate for detecting the outbreak of common diseases; however, it is insufficient for the discovery of novel infectious diseases. In this study, we used COVID-19 as an example to compare the delay time of different tools for identifying disease outbreaks. The results showed that both the abnormal spike in influenza-like illnesses and the peak of online searches of key terms could provide early signals. We emphasize the importance of testing these findings and discussing the broader potential to use syndromic surveillance, internet searches, and social media data together with traditional disease surveillance systems for early detection and understanding of novel emerging infectious diseases.

Measurement-based evaluation of Google/Apple Exposure Notification API for proximity detection in a light-rail tram.

We report on the results of a Covid-19 contact tracing app measurement study carried out on a standard design of European commuter tram. Our measurements indicate that in the tram there is little correlation between Bluetooth received signal strength and distance between handsets. We applied the detection rules used by the Italian, Swiss and German apps to our measurement data and also characterised the impact on performance of changes in the parameters used in these detection rules. We find that the Swiss and German detection rules trigger no exposure notifications on our data, while the Italian detection rule generates a true positive rate of 50% and a false positive rate of 50%. Our analysis indicates that the performance of such detection rules is similar to that of triggering notifications by randomly selecting from the participants in our experiments, regardless of proximity.

qRT-PCR Platforms for Diagnosing and Reporting SARS-CoV-2 Infection in Human Samples.

The protocols herein outline the use of qRT-PCR to detect the presence of SARS-CoV-2 genomic RNA in patient samples. In order to cope with potential fluctuations in supply chain and testing demands and to enable expedient adaptation of reagents and assays on hand, we include details for three parallel methodologies (one- and two-step singleplex and one-step multiplex assays). The diagnostic platforms described can be easily adapted by basic science research laboratories for SARS-CoV-2 diagnostic testing with relatively short turnaround time. For complete details on the use and execution of this protocol, please refer to Vanuytsel et al. (2020).

Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.

The outbreak of the coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, spread worldwide after its emergence in China. Whether rich or poor, all nations are struggling to cope with this new global health crisis. The speed of the threat's emergence and the quick response required from public health authorities and the public itself makes evident the need for a major reform in pandemic surveillance and notification systems. The development and implementation of a graded, individual-level pandemic notification system could be an effective tool to combat future threats of epidemics. This paper describes a prototype model of such a notification system and its potential advantages and challenges for implementation. Similar to other emergency alerts, this system would include a number of threat levels (level 1-5) with a higher level indicating increasing severity and intensity of safety measures (eg, level 1: general hygiene, level 2: enhanced hygiene, level 3: physical distancing, level 4: shelter in place, and level 5: lockdown). The notifications would be transmitted to cellular devices via text message (for lower threat levels) or push notification (for higher threat levels). The notification system would allow the public to be informed about the threat level in real time and act accordingly in an organized manner. New Zealand and the United Kingdom have recently launched similar alert systems designed to coordinate the ongoing COVID-19 pandemic response more efficiently. Implementing such a system, however, faces multiple challenges. Extensive preparation and coordination among all levels of government and relevant sectors are required. Additionally, such systems may be effective primarily in countries where there exists at least moderate trust in government. Advance and ongoing public education about the nature of the system and its steps would be an essential part of the system, such that all members of the public understand the meaning of each step in advance, similar to what has been established in systems for other emergency responses. This educational component is of utmost importance to minimize adverse public reaction and unintended consequences. The use of mass media and local communities could be considered where mobile phone penetration is low. The implementation of such a notification system would be more challenging in developing countries for several reasons, including inadequate technology, limited use of data plans, high population density, poverty, mistrust in government, and tendency to ignore or failure to understand the warning messages. Despite the challenges, an individual-level pandemic notification system could provide added benefits by giving an additional route for notification that would be complementary to existing platforms.

Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19.

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.

Real-time tracking of self-reported symptoms to predict potential COVID-19.

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.

Emergence of a Novel Coronavirus (COVID-19): Protocol for Extending Surveillance Used by the Royal College of General Practitioners Research and Surveillance Centre and Public Health England.

BACKGROUND: The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) have successfully worked together on the surveillance of influenza and other infectious diseases for over 50 years, including three previous pandemics. With the emergence of the international outbreak of the coronavirus infection (COVID-19), a UK national approach to containment has been established to test people suspected of exposure to COVID-19. At the same time and separately, the RCGP RSC's surveillance has been extended to monitor the temporal and geographical distribution of COVID-19 infection in the community as well as assess the effectiveness of the containment strategy. OBJECTIVES: The aims of this study are to surveil COVID-19 in both asymptomatic populations and ambulatory cases with respiratory infections, ascertain both the rate and pattern of COVID-19 spread, and assess the effectiveness of the containment policy. METHODS: The RCGP RSC, a network of over 500 general practices in England, extract pseudonymized data weekly. This extended surveillance comprises of five components: (1) Recording in medical records of anyone suspected to have or who has been exposed to COVID-19. Computerized medical records suppliers have within a week of request created new codes to support this. (2) Extension of current virological surveillance and testing people with influenza-like illness or lower respiratory tract infections (LRTI)-with the caveat that people suspected to have or who have been exposed to COVID-19 should be referred to the national containment pathway and not seen in primary care. (3) Serology sample collection across all age groups. This will be an extra blood sample taken from people who are attending their general practice for a scheduled blood test. The 100 general practices currently undertaking annual influenza virology surveillance will be involved in the extended virological and serological surveillance. (4) Collecting convalescent serum samples. (5) Data curation. We have the opportunity to escalate the data extraction to twice weekly if needed. Swabs and sera will be analyzed in PHE reference laboratories. RESULTS: General practice clinical system providers have introduced an emergency new set of clinical codes to support COVID-19 surveillance. Additionally, practices participating in current virology surveillance are now taking samples for COVID-19 surveillance from low-risk patients presenting with LRTIs. Within the first 2 weeks of setup of this surveillance, we have identified 3 cases: 1 through the new coding system, the other 2 through the extended virology sampling. CONCLUSIONS: We have rapidly converted the established national RCGP RSC influenza surveillance system into one that can test the effectiveness of the COVID-19 containment policy. The extended surveillance has already seen the use of new codes with 3 cases reported. Rapid sharing of this protocol should enable scientific critique and shared learning. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18606.