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Digital proximity tracing has been promoted as a major technological innovation for its potential added benefits of greater speed, wider reach and better scalability compared with traditional manual contact tracing. First launched in Switzerland on 25 June 2020, the SwissCovid digital proximity tracing app has now been in use for more than one year. In light of this milestone, we raise the questions: What is currently known about the role of SwissCovid in mitigating the pandemic? Were the expectations fulfilled? In this review, we will summarise the current state of the literature from empirical studies on the adoption, performance and effectiveness of SwissCovid. The review consists of three sections. The first section summarizes findings from effectiveness studies, which suggest that SwissCovid exposure notifications contributed to preventive actions in 76% of exposure notification recipients and were associated with a faster quarantine time in some SwissCovid user groups. The second describes the public perception and current state of adoption of SwissCovid in Switzerland in light of prevalent misconceptions and overemphasised expectations. the third places the evidence on SwissCovid in an international context. Specifically, we compare key performance indicators of SwissCovid, which are of similar magnitude as for digital proximity tracing apps from other European countries. Using findings from Switzerland, we subsequently derive a preliminary measure of the population-level effectiveness of digital proximity tracing apps. We estimate that exposure notifications may have contributed to the notification and identification of 500 to 1000 SARS-CoV-2-positive app users per month. We explore why this effectiveness estimation is somewhat lower when compared with Germany or the United Kingdom. In light of the presented evidence, we conclude that digital proximity tracing works well in specific contexts, such as in mitigating non-household spread. However, future applications of digital proximity tracing should invest into stakeholder onboarding and increased process automatization – without deviating from the principles of voluntariness and user privacy.

BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization.MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes.ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care.ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.RegistrationISRCTN14990068

Key Points Question What is the possible contribution of digital contact tracing (DCT) apps to the interruption of SARS-CoV-2 transmission chains? Findings This comparative effectiveness study found that the number of DCT app users receiving a quarantine recommendation corresponded to the equivalent of as many as 5% of all mandatory quarantined contacts identified by manual contact tracing in the canton of Zurich, Switzerland. Furthermore, approximately 1 in 11 notification triggers led to SARS-CoV-2 testing of an exposed proximity contact who subsequently had positive test results. Meaning These findings suggest that DCT apps can make a relevant contribution to transmission prevention, with the potential to scale as more persons use the apps., 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., This data-informed simulation study estimates key populations and performance indicators along the exposure notification cascade of the SwissCovid digital contact tracing app in September and October 2020 in Zurich, Switzerland.

ImportanceDigital proximity tracing (DPT) apps were released in several countries to help interrupt SARS-CoV-2 transmission chains in the population. However, the impact of DPT on pandemic mitigation still remains to be demonstrated.ObjectiveTo estimate key populations and performance indicators along the DPT app notification cascade in a clearly defined regional (Canton of Zurich, using all of Switzerland as a comparison) and temporal context (September/October 2020).DesignPublicly available administrative and research data, including key DPT performance indicators, SARS-CoV-2 testing statistics, infoline call statistics, and observational study data, were compiled. A model of the DPT notification cascade was developed and key performance indicators for DPT processes were defined. Subpopulation sizes at each cascade step were estimated using data triangulation. Resulting estimates were systematically checked for internal consistency and consistency with other up- or downstream estimates in the cascade. Stochastic simulations were performed to explore robustness of results.ResultsFor the Canton of Zurich, we estimate that 537 app users received a positive SARS-CoV-2 test in September 2020, of whom 324 received and entered a CovidCode. This triggered an app notification for an estimated 1374 proximity contacts and led to 722 infoline calls. In total, 170 callers received a quarantine recommendation, and 30 app users tested positive for SARS-CoV-2 after an app notification, reflecting a performance above the national level.Based on this quantification, key performance indicators were evaluated. For September 2020, these analyses suggest that SwissCovid triggered quarantine recommendations in the equivalent of 5% of all exposed contacts placed in quarantine by manual contact tracing. Per 11 CovidCodes entered in the app, we estimate that almost 1 contact tested positive for SARS-CoV-2 upon app notification.However, longitudinal indicator analyses demonstrate bottlenecks in the notification cascade, as capacity limits were reached due to large increases in SARS-CoV-2 incidence in October 2020.ConclusionAlthough requiring confirmation, our estimations on the number of notified proximity contacts receiving quarantine recommendations or testing positive after notification suggest relevant contributions to mitigating the pandemic. Increasing SwissCovid app uptake and improving notification cascade performance may further enhance its impact.Key pointsQuestionWhat is the real-life impact of Digital proximity tracing (DPT) apps on interrupting SARS-CoV-2 transmission chains?FindingsThis data-informed simulation study found that, in the canton of Zurich, the number of app notified persons receiving a quarantine recommendation corresponds to the equivalent of up to 5% of all mandatory quarantined contacts identified by manual contact tracing. Furthermore, about 1 in 11 notification triggers led to SARS-CoV-2 testing of an exposed proximity contact who was consecutively tested positive.MeaningDPT apps exert a measurable impact that will further scale as more persons use the apps.

Additional file 4. GRADE evidence profile.

Additional file 1. PICO, Search strategy, List of excluded studies.

Additional file 3. Full results.

Additional file 2. Risk of Bias assessment details.

To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses.One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.

Background Isolation is an indispensable measure to contain the SARS-CoV-2 virus, but it may have a negative impact on mental health and overall wellbeing. Evidence on the isolation experience, facilitating and complicating factors is needed to mitigate negative effects. Methods and findings This observational, population-based cohort study enrolled 1547 adults from the general population with SARS-CoV-2 infection reported to authorities between 27 February 2020 and 19 January 2021 in Zurich, Switzerland. We assessed the proportion of individuals reporting symptoms of depression and anxiety before, during and after isolation (by DASS-21), and queried worries, positive experiences, and difficulties. We analyzed the association of these outcomes with socio-demographics using ordinal regression. Additionally, we report free-text statements by participants to capture most important aspects of isolation. The proportion of participants affected by depression or anxiety increased during isolation from 10·0% to 17·1% and 9·1% to 17·6%, respectively. Ordinal regression showed that taking care of children increased the difficulty of isolation (OR 2·10, CI 1·43–3·08) and risk of non-compliance (OR 1·63, CI 1·05–2·53), especially in younger participants. A facilitating factor that individuals commonly expressed was receiving more support during isolation. Conclusion Isolation due to SARS-CoV-2 presents a mental burden, especially for younger individuals and those taking care of children. Public health authorities need to train personnel and draw from community-based resources to provide targeted support, information, and guidance to individuals during isolation. Such efforts could alleviate the negative impact isolation has on the mental and physical health of individuals and ensure compliance of the population with recommendations.

Summary Background Since the benefit–harm balance of adding inhaled corticosteroids to long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles. Methods Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care. Findings Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54–83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40–91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per μL, patients with a BEC of 150 cells per μL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32–95% in those aged 40–79 years and 41–93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per μL or more at 52–86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%. Interpretation The net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids. Funding None.

BackgroundDigital proximity tracing (DPT) apps may warn exposed individuals faster than manual contact tracing (MCT), leading to earlier interruption of transmission chains through quarantine. However, it is yet unclear whether these apps lead to a reduction in transmissions under real-world conditions. This study aimed at evaluating whether the SwissCovid DPT app is effective in warning close contacts of SARS-CoV-2 infected cases and prompting them to quarantine earlier.MethodsA population-based sample of adult index cases and close contacts identified through MCT and enrolled in the Zurich SARS-CoV-2 Cohort study were surveyed regarding use of the SwissCovid app and SARS-CoV-2 exposure setting. We analyzed ooutcomes related to app effectiveness and adherence (i.e., receipt and uploading of notification codes by index cases; receipt of app warnings and steps taken by close contacts). Furthermore, we performed adjusted time-to-event analyses stratified by exposure setting to estimate the effect of the app on time between relevant exposure and entering quarantine among close contacts.FindingsWe included 393 index cases and 261 close contacts in the analysis. Among index cases using SwissCovid, 88% reported receiving and uploading a notification code in the app to trigger a warning among proximity contacts. Among close contacts using the app, 38% reported receiving an app warning due to the risk exposure. We found that non-household contacts who were notified by the app started quarantine at a median of 2 days after exposure, while those not notified started quarantine at a median of 3 days. In stratified multivariable analyses, app notified contacts had a greater probability of going into quarantine earlier than those without app notification (HR 1·53, 95% CI 1·15-2·03).InterpretationOur study showed that non-household contacts notified by the app started quarantine one day earlier than those not notified by the app. These findings constitute the first evidence that DPT may reach exposed contacts faster than MCT, leading to earlier quarantine and potential interruption of SARS-CoV-2 transmission chains.FundingCantonal Health Directorate Zurich, University of Zurich Foundation and the Swiss Federal Office of Public Health.

BACKGROUND Digital proximity tracing apps have been released to mitigate the transmission of SARS-CoV-2, the virus known to cause COVID-19. However, it remains unclear how the acceptance and uptake of these apps can be improved. OBJECTIVE This study aimed to investigate the coverage of the SwissCovid app and the reasons for its nonuse in Switzerland during a period of increasing incidence of COVID-19 cases. METHODS We collected data between September 28 and October 8, 2020, via a nationwide online panel survey (COVID-19 Social Monitor, N=1511). We examined sociodemographic and behavioral factors associated with app use by using multivariable logistic regression, whereas reasons for app nonuse were analyzed descriptively. RESULTS Overall, 46.5% (703/1511) of the survey participants reported they used the SwissCovid app, which was an increase from 43.9% (662/1508) reported in the previous study wave conducted in July 2020. A higher monthly household income (ie, income >CHF 10,000 or >US $11,000 vs income ≤CHF 6000 or CONCLUSIONS Eliminating technical hurdles and communicating the benefits of digital proximity tracing apps are crucial to promote further uptake and adherence of such apps and, ultimately, enhance their effectiveness to aid pandemic mitigation strategies.

Background Digital proximity tracing (DPT) apps have been released to mitigate SARS-CoV-2 transmission. But it remains unclear how their acceptance and uptake can be improved. The aim of this study was to investigate SwissCovid app coverage and reasons for not using the app in Switzerland during a time of increasing SARS-CoV-2 incidence. Methods By use of data collected between 28.09.2020 to 08.10.2020 for a nationwide online panel survey (Covid-19 Social Monitor, n=1’511 participants), socio-demographic and behavioral factors associated with app usage were examined using multivariable logistic regression. Reasons for app non-use were analyzed descriptively. Results Overall, 46.5% of participants reported using the SwissCovid app (up from 43.9% in a study wave conducted in July 2020). A higher monthly household income (e.g. OR 1.92 [1.40-2.64] for an income >CHF 10’000 vs. an income ≤ CHF 6’000), more frequent internet use (e.g., daily (reference) vs. less than weekly OR 0.37 [0.16-0.85]), better adherence to mask-wearing recommendations (e.g., always or most of the time (reference) vs. rarely or never OR 0.28 [0.15-0.52]), and being a non-smoker (OR 1.32 [1.01-1.71]) were associated with an increased likelihood for app uptake. Citizenship status (e.g., non-Swiss citizenship 0.61 [0.43-0.87] vs. Swiss citizenship only), and language region (French 0.61 [0.46-0.80], vs. Swiss German) were associated with a lower app uptake probability. In a randomly selected subsample (n=711) with more detailed information, higher levels of trust in government and health authorities were additionally associated with a higher app uptake probability (e.g., OR 3.13 [1.58-6.22] for high vs. low trust (reference)). The most frequent reasons for app non-use was lack of perceived benefit of the app (36.8%), 22.8% reported to have no compatible phone, and 22.4% had privacy concerns. Conclusion Removing technical hurdles and communicating the benefits of DPT-apps are crucial to promote further uptake, compliance, and ultimately to enhance effectiveness of DPT-apps for pandemic mitigation.

Background/research question: Patient-centered decision-making in preventive medicine involves the consideration of an individual's baseline risks for disease, expected treatment effects and outcomes, and personal preferences. Whether a treatment ultimately provides a net benefit strongly [for full text, please go to the a.m. URL], Nützliche patientenrelevante Forschung; 21. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

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 2019 (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.

Supplemental material, Supplementary_material for Net benefit of statins for primary prevention of cardiovascular disease in people 75 years or older: a benefit–harm balance modeling study by Henock G. Yebyo, Hélène E. Aschmann, Dominik Menges, Cynthia M. Boyd and Milo A. Puhan in Therapeutic Advances in Chronic Disease

Background: We determined the risk thresholds above which statin use would be more likely to provide a net benefit for people over the age of 75 years without history of cardiovascular disease (CVD). Methods: An exponential model was used to estimate the differences in expected benefit and harms in people treated with statins over a 10-year horizon versus not treated. The analysis was repeated 100,000 times to consider the statistical uncertainty and produce a distribution of the benefit–harm balance index from which we determined the 10-year CVD risk threshold where benefits outweighed the harms. We considered treatment estimates from trials and observational studies, baseline risks, patient preferences, and competing risks of non-CVD death, and statistical uncertainty. Results: Based on average preferences, statins were more likely to provide a net benefit at a 10-year CVD risk of 24% and 25% for men aged 75–79 years and 80–84 years, respectively, and 21% for women in both age groups. However, these thresholds varied significantly depending on differences in individual patient preferences for the statin-related outcomes, with interquartile ranges of 21–33% and 23–36% for men aged 75–79 years and 80–84 years, respectively, as well as 20–32% and 21–32% for women aged 75–79 years and 80–84 years, respectively. Conclusions: Statins would more likely provide a net benefit for primary prevention in older people taking the average preferences if their CVD risk is well above 20%. However, the thresholds could be much higher or lower depending on preferences of individual patients, which suggests more emphasis should be placed on individual-based decision-making, instead of recommending statins for everyone based on a single or a small number of thresholds.

The brains of sengis (elephant shrews, order Macroscelidae) have long been known to contain a hippocampus that in terms of allometric progression indices is larger than that of most primates and equal in size to that of humans. In this report, we provide descriptions of hippocampal cytoarchitecture in the eastern rock sengi (Elephantulus myurus), of the distributions of hippocampal calretinin, calbindin, parvalbumin, and somatostatin, of principal neuron numbers, and of cell numbers related to proliferation and neuronal differentiation in adult hippocampal neurogenesis. Sengi hippocampal cytoarchitecture is an amalgamation of characters that are found in CA1 of, e.g., guinea pig and rabbits and in CA3 and dentate gyrus of primates. Correspondence analysis of total cell numbers and quantitative relations between principal cell populations relate this sengi to macaque monkeys and domestic pigs, and distinguish the sengi from distinct patterns of relations found in humans, dogs, and murine rodents. Calretinin and calbindin are present in some cell populations that also express these proteins in other species, e.g., interneurons at the stratum oriens/alveus border or temporal hilar mossy cells, but neurons expressing these markers are often scarce or absent in other layers. The distributions of parvalbumin and somatostatin resemble those in other species. Normalized numbers of PCNA+ proliferating cells and doublecortin-positive (DCX+) differentiating cells of neuronal lineage fall within the overall ranges of murid rodents, but differed from three murid species captured in the same habitat in that fewer DCX+ cells relative to PCNA+ were observed. The large and well-differentiated sengi hippocampus is not accompanied by correspondingly sized cortical and subcortical limbic areas that are the main hippocampal sources of afferents and targets of efferents. This points to intrinsic hippocampal information processing as the selective advantage of the large sengi hippocampus.