SARS-CoV-2 quarantine mandated by contact tracing: burden and infection rate among close contacts in Zurich, Switzerland, 2020-2021 (preprint)

ObjectivesBefore vaccines and effective treatments were available, quarantine of close contacts was important to limit the spread of SARS-CoV-2. To evaluate potential benefits and harms of quarantine, we aimed to estimate infection rates and describe experiences and mental health among persons in mandated quarantine during the early SARS-CoV-2 pandemic. MethodsWe invited adults in mandated quarantine after an exposure to SARS-CoV-2 identified through contact tracing of the Canton of Zurich, Switzerland, between August 2020 and January 2021. Participants completed two questionnaires and received up to two SARS-CoV-2 polymerase chain reaction tests, during and at the end of quarantine. ResultsAmong 395 participants, quarantine duration ranged from 2 to 20 days. By day 11 since the last contact, 11.1% [95% CI 8.4%-14.7%] were infected with SARS-CoV-2. The proportion of participants with symptoms of depression doubled from 9.3% before quarantine to 18.9% during quarantine, and 12.1% reported quarantine was very or extremely difficult. ConclusionsAlthough quarantine was only moderately burdensome for most participants, some experienced significant difficulties and burden. Policymakers need to balance infection control with potential harms placed on individuals.

Persistent humoral immunity in children and adolescents throughout the COVID-19 pandemic (June 2020 to July 2022): a prospective school-based cohort study (Ciao Corona) in Switzerland (preprint)

Objectives: To assess the longitudinal development of humoral immunity in children and adolescents during the COVID-19 pandemic, with a particular focus on how anti-spike IgG antibodies and neutralising response changed during the first Omicron peak (December 2021 to May 2022). Design: Prospective school-based study during the COVID-19 pandemic (June 2020 to July 2022) including five testing rounds with corresponding cross-sectional cohorts and a longitudinal cohort who participated in at least four rounds. Setting: 55 randomly selected schools in the Canton of Zurich, Switzerland. Participants: Between 1875 to 2500 children and adolescents per testing round and 751 in the longitudinal cohort. Main outcome measures: Development of SARS-CoV-2 seroprevalence, anti-spike IgG antibodies and neutralising antibody response over time, persistence of antibodies and variation of antibody levels in individuals only infected, vaccinated or with hybrid immunity during the early Omicron period. Results: By July 2022 96.9% (95% credible interval [CrI] 95.2 to 98.1%) of children and adolescents had anti-spike IgG antibodies against SARS-CoV-2. The substantial increase in seroprevalence during the first peak of the Omicron wave was largely driven by primary infections in mostly unvaccinated children under the age of 12 (28.4% [95% CrI 24.2 to 33.2%] in December 2021, to 95.7% [95% CrI 93.4 to 97.4%] in July 2022). This stands in contrast to adolescents aged 12 years and older (69.4% [95% CrI 64.0 to 75.4%] in December 2021 to 98.4% [95% CrI 97.3 to 99.2%] in July 2022), who were eligible for vaccination since June 2021. Children and adolescents with hybrid immunity or immunity from vaccination had high anti-spike IgG titres (median Mean Fluorescence Intensity (MFI) ratio of 136.2 [Inter Quartile Range [IQR]: 121.9 to 154.3] and 127.6 [IQR: 114.1 to 151.0]) and strong neutralising responses (e.g., anti-Omicron 98.9% [95% Confidence Interval [CI] 96.0 to 99.7%] and 81.6% [95% CI 74.9 to 86.9%]). Meanwhile, infected but unvaccinated children and adolescents had substantially lower anti-spike IgG titres (median MFI ratio of 54.8 [IQR: 22.8 to 89.8]) and neutralising responses (e.g., anti-Omicron 64.9% [95% CI 59.8 to 69.7%]). Conclusion: These findings show that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity and boosted anti-spike IgG titres and neutralising capacity in children and adolescents. This was particularly driven by unvaccinated children (<12 years), who became seropositive due to the highly infectious Omicron variant. Nevertheless, during the entire study parents of only one adolescent reported hospital stay of less than 24 hours related to a possible acute infection.

Post COVID-19 Condition, Work Ability and Occupational Changes: Results from a Population-based Cohort (preprint)

BackgroundEvidence from population-based studies on the impact of post COVID-19 condition (PCC) on ability to work is limited but critical due to its high prevalence among individuals of working-age. ObjectiveTo evaluate the association between PCC, work ability, and occupational changes. DesignPopulation-based, longitudinal cohort. SettingGeneral population, Canton of Zurich, Switzerland. Participants672 adults of working-age with SARS-CoV-2 infection. MeasurementsCurrent work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), as well as PCC-related occupational changes at one year after infection. ResultsThere was very strong evidence that current work ability scores were 0.62 (95% confidence interval (CI) 0.30 to 0.95) points lower among those with PCC compared to those without. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (odds ratio (OR) 0.30, 95% CI 0.20 to 0.46) and mental (OR 0.40, 0.27 to 0.62) demands among those with PCC compared to those without. Higher age and history of psychiatric diagnosis were associated with a more substantial reduction in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce and 43% of those with PCC-related occupational changes reporting financial difficulties as a result. LimitationsSelection, use of self-reported outcome measures, and limited generalizability to individuals with most severe COVID-19 or following vaccination. ConclusionsThese findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity. Primary Funding SourceFederal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland. Study RegistrationISRCTN14990068.

Longitudinal Humoral and Cell-Mediated Immune Responses in a Population-Based Cohort in Zurich, Switzerland between March and June 2022 - Evidence for Protection against Omicron SARS-CoV-2 Infection by Neutralizing Antibodies and Spike-specific T cell responses (preprint)

Background: The correlate(s) of protection against SARS-CoV-2 remain incompletely de-fined. Additional information regarding the combinations of antibody and T cell-mediated immunity which can protect against (re)infection are needed. Methods: We conducted a population-based, longitudinal cohort study including 1044 individuals of varying SARS-CoV-2 vaccination and infection statuses. We assessed Spike (S)- and Nucleocapsid (N)-IgG and wildtype, delta, and omicron neutralizing antibodies. In a subset of 328 individuals, we evaluated S, Membrane (M) and N-specific T cells. 3 months later, we reassessed antibody (n=964) and T cell (n=141) responses and evaluated factors associated with protection from (re)infection. Results: At study start, >98% of participants were S-IgG seropositive. N-IgG and M/N-T cell responses increased over time, indicating viral (re)exposure, despite existing S-IgG. Com-pared to N-IgG, M/N-T cells were a more sensitive measure of viral exposure. N-IgG titers in the top 33% of participants, omicron neutralizing antibodies in the top 25%, and S-specific T cell responses were all associated with reduced likelihood of (re)infection over time. Conclusions: Population-level SARS-CoV-2 immunity is S-IgG-dominated, but heterogenous. M/N T cell responses can distinguish previous infection from vaccination, and monitoring a combination of N-IgG, omicron neutralizing antibodies and S-T cell responses may help estimate protection against SARS-CoV-2 (re)infection.

Comparative adverse effects, perceptions and attitudes related to BNT162b2, mRNA1273, or JNJ-78436735 SARS-CoV-2 vaccines: A population-based longitudinal cohort (preprint)

Importance Long-term control of SARS-CoV-2 requires effective vaccination strategies. This has been challenged by public mistrust and spread of misinformation regarding vaccine safety. Hence, better understanding and communication on the longer-term and comparative experiences of general population individuals following SARS-CoV-2 vaccination are required. Objective To evaluate and compare self-reported adverse effects following SARS-CoV-2 vaccination, participants’ perceptions regarding vaccinations and their compliance with recommended public health measures. Design, Setting and Participants Population-based longitudinal cohort of 575 adults, randomly selected from all individuals presenting to the reference vaccination center of the Canton of Zurich, Switzerland, for receipt of BNT162b2, mRNA1273, or JNJ-78436735. Exposures BNT162b2, mRNA1273, or JNJ-78436735 vaccines. Main Outcomes and Measures Primary outcomes included period prevalence, onset, duration, and severity of self-reported adverse effects over 12 weeks following vaccination with a specific focus on the proportion of participants reporting allergic reactions, menstrual irregularities, or cardiac adverse effects, or requiring hospitalization. Secondary outcomes included risk factors associated with reporting adverse effects, perception of vaccine importance, trust in public health authorities and pharmaceutical companies, and compliance with recommended public health measures. Results 454 (79.0%) participants reported at least one adverse effect during 12 weeks after vaccination. Prevalence was highest among mRNA-1273 recipients (88.7% vs. 77.3% after BNT162b2, 69.1% after JNJ-78436735). Most adverse effects were systemic (72%), occurred within 24 hours (67.9%), and resolved in less than three days (76.3%). 85.2% were reported as mild or moderate. Allergic reactions were reported by 0.4% of participants, hospitalizations by 0.7%, cardiac adverse effects by 1.4%. Menstrual irregularities were reported by 9% of female participants younger than 50 years. Female sex, younger age, higher education, and receipt of mRNA-1273 were associated with reporting adverse effects. Compared to JNJ-78436735 recipients, a higher proportion of mRNA vaccine recipients agreed that vaccination is important (87.5% vs. 28.5%), and trusted public health authorities (80.2% vs. 30.3%) and pharmaceutical companies (71.7% vs. 23.6%). Conclusions and Relevance Our population-based cohort provided real-world data on self-reported adverse effects following SARS-CoV-2 vaccination and highlights the importance of transparent communication regarding adverse effects and building trust in public health authorities to ensure successful future vaccination campaigns. Main Points Our representative population-based cohort study demonstrated the safety of three SARS-CoV-2 vaccines and provides real-world estimates on adverse effect incidence.Transparent communication of expected adverse effects to vaccine-seeking individuals is pivotal to build trust in current or future vaccination campaigns.

Post COVID-19 condition after Wildtype, Delta, and Omicron variant SARS-CoV-2 infection and vaccination: pooled analysis of two population-based cohorts (preprint)

BackgroundPost COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. Further evidence is needed on the risk of PCC after vaccination and infection with newer variants. This study aimed to evaluate the prevalence and severity of PCC across different variants and vaccination histories. MethodsWe used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses. FindingsWe found strong evidence that vaccinated individuals infected with Omicron had a reduced risk of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The risk among non-vaccinated individuals was similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants. InterpretationThe risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies. FundingSwiss School of Public Health (SSPH+), University of Zurich Foundation, Cantonal Department of Health Zurich, Swiss Federal Office of Public Health Study registrationsISRCTN14990068, ISRCTN18181860 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched MEDLINE, EMBASE, and medRxiv for primary studies assessing the prevalence and symptoms associated with post COVID-19 condition (PCC) after infection with different SARS-CoV-2 variants and among infected individuals with and without prior vaccination. We used a specific search strategy limited to the timeframe between Jan 01, 2020, and Aug 29, 2022, without language restriction (reported in Supplementary Table S1). We further searched identified systematic reviews for additional references. We screened 221 unique records and identified four studies investigating the association of Delta or Omicron variant infections and 11 studies investigating the association of prior vaccination with PCC. Current evidence is uncertain whether infection with emerging variants may be associated with a reduction of the risk of developing PCC. Two studies found a decreased risk of PCC with Omicron compared to Delta infection, or to individuals infected during any prior wave. One study found a lower risk of PCC with Alpha compared to Wildtype SARS-CoV-2, but an increased risk among those infected with the Delta or Omicron variant. One study primarily examined symptom clusters across different waves. All identified studies defined PCC as symptoms occurring at [≥]4 weeks or [≥]12 weeks after infection, and were conducted among hospitalised patients, healthcare workers, or users of the United Kingdom ZOE symptom app. Evidence regarding the preventive effects of vaccination on PCC was of higher certainty, with eight out of 11 studies reporting a substantially reduced PCC incidence with mRNA- and adenovirus vector-based vaccines. The magnitude of the effect in these studies varied, with estimated adjusted odds ratios ranging from 0.22 to 0.85. Nonetheless, three studies found no difference between vaccinated and non-vaccinated infected individuals, including two of three studies evaluating PCC at six months after infection. The third study with a six-month horizon found a higher odds ratio than any other study reporting a reduction at [≥]4 weeks or [≥]12 weeks. Study populations and designs varied strongly, and only one study evaluated the independent effects of SARS-CoV-2 variants and vaccination. Added value of this studyThis study investigates the association of PCC with infection with Delta and Omicron variants and prior vaccination compared to Wildtype SARS-CoV-2 infection among unvaccinated individuals. We found that infection with the Omicron variant and prior vaccination were associated with a lower risk of developing PCC six months after infection. Compared to previous work, this study is the first to evaluate PCC with a longer-term follow-up, while simultaneously evaluating the risk reduction by Delta and Omicron variants and prior vaccination on PCC. By relying on prospectively collected data from two representative population-based cohorts, we were able to provide an in-depth analysis of the longer-term risk reduction through prior vaccination and novel variants, the severity of PCC-related symptoms, and symptom clusters across pandemic waves between 2020 and early 2022. Implications of all the available evidenceIn conjunction with existing evidence, our study suggests that infection with the Omicron variant and prior vaccination are likely to substantially reduce the risk of developing PCC compared to infection with Wildtype SARS-CoV-2 without prior vaccination. We demonstrate that this risk reduction persists up to six months after infection, and that PCC-related symptoms are reduced to a similar extent across different levels of severity. However, the risk of having mild to even potentially severe PCC six months after infection is not eliminated. Hence, vaccinations will likely continue to be an important mainstay in the management of the further course of the pandemic. The prevention of further infection and PCC may still provide important benefits for public health, even if SARS-CoV-2 further evolves to cause milder infections and becomes endemic. Therefore, information from this study will be crucial to guide vaccination strategies and decisions on timing and enforcement of public health measures worldwide.

Natural course of post COVID-19 condition and implications for trial design and outcome selection: A population-based longitudinal cohort study (preprint)

Background: Evidence from population-based studies on the longer-term natural course of post COVID-19 condition is limited, but crucial for informing patients and healthcare providers and for effectively designing clinical trials. Objectives: To evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. Design: Population-based, longitudinal cohort. Setting: General population, Canton of Zurich, Switzerland. Patients: 1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. Measurements: Changes in self-reported health status over time, factors associated with persistence of non-recovery, and prevalence and excess risk of symptoms at 6 and 12 months post-infection compared to non-infected individuals. Results: 25% of SARS-CoV-2 infected individuals did not recover by 6 months. Of those, 67% and 58% also did not recover at 12 and 18 months after infection, respectively. Hospitalization for acute COVID-19, pre-existing fatigue and pain or discomfort, and presence of specific systemic, cardiovascular, or musculoskeletal symptoms at 6 months were associated with persistent non-recovery. Symptom prevalence was higher among infected individuals compared to non-infected individuals at 6 months (adjusted risk difference (aRD)=17%) and 12 months (aRD=20%). aRDs for individual symptoms ranged from 2% to 12%, with the highest excess risks observed for altered taste or smell, post-exertional malaise, fatigue, and reduced concentration and memory. Limitations: We relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. Conclusion: These findings emphasize the need for effective interventions to reduce the burden of post COVID-19 condition. They further demonstrate the importance of using multiple outcome measures and of considering the expected rates of natural recovery and heterogenous patient trajectories in the design and interpretation of clinical trials.

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021 (preprint)

ImportanceWhile much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. ObjectiveTo estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery DesignWe jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. ResultsAnalyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevanceThe occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021? FindingsGlobally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered. MeaningThe substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Heterogenous Cellular and Humoral Immune Trajectories after SARS-CoV-2 Infection: Compensatory Responses in a Population-Based Cohort (preprint)

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.

Burden of Post-COVID-19 Syndrome and Implications for Healthcare Service Planning: A Population-based Cohort Study (preprint)

Background Longer-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. Methods This 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. Results Symptoms 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. Conclusions In 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. Registration ISRCTN14990068

The role of the SwissCovid digital contact tracing app during the pandemic response: results for the Canton of Zurich (preprint)

Importance: Digital contact tracing (DCT) apps were released in several countries to help interrupt SARS-CoV-2 transmission chains in the population. However, the impact of DCT on pandemic mitigation still remains to be demonstrated. Objective: To estimate key populations and performance indicators along the DCT app notification cascade in a clearly defined regional (Canton of Zurich, using all of Switzerland as a comparison) and temporal context (September/October 2020). Design: Publicly available administrative and research data, including key DCT performance indicators, SARS-CoV-2 testing statistics, infoline call statistics, and observational study data, were compiled. A model of the DCT notification cascade was developed and key performance indicators for DCT 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. Results: For 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. Conclusion: Although 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.

Digital proximity tracing app notifications lead to faster quarantine in non-household contacts: results from the Zurich SARS-CoV-2 Cohort Study (preprint)

Background: Digital 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. Methods: A 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. Findings: We 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). Interpretation: Our 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.

Early Evidence of Effectiveness of Digital Contact Tracing for SARS-CoV-2 in Switzerland (preprint)

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.

Are COVID-19 proximity tracing apps working under real-world conditions? Indicator development and assessment of drivers for app (non-)use (preprint)

Digital proximity tracing (DPT) apps have been released to mitigate SARS-CoV-2 transmission, but it remains unclear how their effectiveness should be monitored. The aim of this study was to formalize indicators for measuring the fulfillment of assumptions for appropriate proximity tracing app functioning. Six indicators were developed to monitor the SwissCovid app functioning and effectiveness in the Swiss population. Using official statistics and survey data, we calculated indicator values and examined socio-demographic factors associated with the SwissCovid app utilization. Indicators show that 1 in 3 adults in Switzerland have downloaded the app. However, only 15% of new cases also triggered DPT-app notifications, and indicators also reveal ignored app notifications. In the full survey sample (n=2098), higher monthly household income or being a non-smoker were associated with higher SwissCovid app uptake; older age or having a non-Swiss nationality with a lower uptake. In a subsample including more detailed information (n=701), high trust in health authorities was associated with higher SwissCovid app uptake. The indicators help to monitor key drivers of DPT-apps effectiveness and hint to non-compliance issues. Streamlining procedures, removing technical hurdles, and communicating the usefulness of DPT-apps are crucial to promote uptake, compliance, and ultimately effectiveness of DPT-apps for pandemic mitigation.