Search

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents' education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales., Conclusion: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group., What Is Known: • Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being. • HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples., What Is New: • Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. • Public health strategies to improve mental health may be effective in improving HRQOL in children., (© 2024. The Author(s).)

Numerous clinical parameters link to severe coronavirus disease 2019, but factors that prevent symptomatic disease remain unknown. We investigated the impact of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and endemic human coronavirus (HCoV) antibody responses on symptoms in a longitudinal children cohort ( n = 2,917) and a cross-sectional cohort including children and adults ( n = 882), all first exposed to SARS-CoV-2 (March 2020 to March 2021) in Switzerland. Saliva ( n = 4,993) and plasma ( n = 7,486) antibody reactivity to the four HCoVs (subunit S1 [S1]) and SARS-CoV-2 (S1, receptor binding domain, subunit S2 [S2], nucleocapsid protein) was determined along with neutralizing activity against SARS-CoV-2 Wuhan, Alpha, Delta, and Omicron (BA.2) in a subset of individuals. Inferred recent SARS-CoV-2 infection was associated with a strong correlation between mucosal and systemic SARS-CoV-2 anti-spike responses. Individuals with pre-existing HCoV-S1 reactivity exhibited significantly higher antibody responses to SARS-CoV-2 in both plasma (IgG regression coefficients = 0.20, 95% CI = [0.09, 0.32], P < 0.001) and saliva (IgG regression coefficient = 0.60, 95% CI = [0.088, 1.11], P = 0.025). Saliva neutralization activity was modest but surprisingly broad, retaining activity against Wuhan (median NT50 = 32.0, 1Q-3Q = [16.4, 50.2]), Alpha (median NT50 = 34.9, 1Q-3Q = [26.0, 46.6]), and Delta (median NT50 = 28.0, 1Q-3Q = [19.9, 41.7]). In line with a rapid mucosal defense triggered by cross-reactive HCoV immunity, asymptomatic individuals presented with higher pre-existing HCoV-S1 activity in plasma (IgG HKU1, odds ratio [OR] = 0.53, 95% CI = [0.29,0.97], P = 0.038) and saliva (total HCoV, OR = 0.55, 95% CI = [0.33, 0.91], P = 0.019) and higher SARS-CoV-2 reactivity in saliva (IgG S2 fold change = 1.26, 95% CI = [1.03, 1.54], P = 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses., Competing Interests: H.F.G. reports having received honoraria from Gilead Sciences, Merck, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis for serving on DSMB and/or advisory boards and has received a travel grant from Gilead Sciences. In addition, he has received grants from the Swiss National Science Foundation (SNSF), the Swiss HIV Cohort Study, the Yvonne Jacob Foundation, and the NIH and unrestricted research grants from Gilead Sciences, all paid to the institution. A.T. has received honoraria from Roche Diagnostics for consultant activity, grants from the SNSF, the Swiss HIV Cohort Study, and the Pandemiefonds of the UZH foundation, and unrestricted research grants from Gilead Sciences. I.A.A. has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, and a grant from Promedica foundation. R.D.K. has received grants from SNSF, the National Institutes of Health, and Gilead Sciences. C.P. has received a grant from the Collegium Helveticum.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study "Ciao Corona", we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3-98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 ., (© 2023. The Author(s).)

Purpose: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time., Methods: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models., Results: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake., Conclusions: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed., (© 2023. The Author(s).)

Objectives: To describe the frequency of and reasons for changes in healthcare utilization in those requiring ongoing treatment, and to assess characteristics associated with change, during the second wave of the pandemic. Methods: Corona Immunitas e-cohort study (age ≥20 years) participants completed monthly questionnaires. We compared participants reporting a change in healthcare utilization with those who did not using descriptive and bivariate statistics. We explored characteristics associated with the number of changes using negative binomial regression. Results: The study included 3,190 participants from nine research sites. One-fifth reported requiring regular treatment. Among these, 14% reported a change in healthcare utilization, defined as events in which participants reported that they changed their ongoing treatment, irrespective of the reason. Reasons for change were medication changes and side-effects, specifically for hypertension, or pulmonary embolism treatment. Females were more likely to report changes [Incidence Rate Ratio (IRR) = 2.15, p = 0.002]. Those with hypertension were least likely to report changes [IRR = 0.35, p = 0.019]. Conclusion: Few of those requiring regular treatment reported changes in healthcare utilization. Continuity of care for females and chronic diseases besides hypertension must be emphasized., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Harju, Speierer, Jungo, Levati, Baggio, Tancredi, Noor, Rodondi, Cullati, Imboden, Keidel, Witzig, Frank, Kohler, Kahlert, Crivelli, Amati, Albanese, Kaufmann, Frei, von Wyl, Puhan, Probst-Hensch, Michel, Rodondi and Chocano-Bedoya.)

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19., (© 2023. The Author(s).)

Background: Despite strong recommendations for coronavirus disease 2019 (Covid-19) vaccination by multiple sclerosis (MS) organizations, some persons with MS (pwMS) remain vaccine hesitant. The Swiss MS Registry conducted a survey to explore Covid-19 vaccine hesitancy, self-reported side effects and changes in MS symptoms following vaccination in adult pwMS., Methods: Self-reported data were analyzed cross-sectionally. Multivariable logistic regression was used to explore participant characteristics associated with Covid-19 vaccine hesitancy., Results: Of 849 respondents, 73 (8.6%) were unvaccinated. Hesitation to vaccinate was most often a personal preference (N = 42, 57.53%). Factors negatively associated with vaccine hesitancy included older age (OR = 0.97 per year, 95% CI [0.94, 0.99]) and regularly seeing healthcare professionals (OR = 0.25, 95% CI [0.07, 0.85]). A history of confirmed Covid-19 infection (OR = 3.38, 95% CI [1.69, 6.77]) and being underweight (OR = 4.50, 95% CI [1.52, 13.36]) were positively associated with vaccine hesitancy. Of 768 participants who provided information, 320 (41.2%) and 351 (45.2%) reported vaccination side effects after the first and second vaccinations, respectively. Changes in MS symptoms were reported by 49 (6.3%) participants after the first and 67 (9.0%) participants after the second vaccination, and were most often described as increased or new-onset fatigue (N = 17/49 (34.7%) after the first and N = 21/67 (31.3%) after the second dose)., Conclusions: Covid-19 vaccine hesitancy was low among surveyed pwMS. The risk of vaccine hesitancy was higher among younger pwMS, those with a history of Covid-19 infection, and those without regular contact with healthcare professionals., Competing Interests: Declaration of Competing Interest Mina Stanikić reports employment by Roche branch in Serbia, Roche d.o.o., from February 2019 to February 2020. Christian P Kamm has received honoraria for lectures as well as research support from Biogen, Novartis, Almirall, Teva, Merck, Sanofi Genzyme, Roche, Janssen, Eli Lilly, Celgene and the Swiss MS Society. Ente Ospedaliero Cantonale (employer) received compensation for Chiara Zecca's speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. Chiara Zecca is recipient of a grant for senior researchers provided by AFRI (Area Formazione accademica, Ricerca e Innovazione), EOC. Ente Ospedaliero Cantonale (employer) received compensation for Claudio Gobbi's speaking activities, consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. Anke Salmen has received speaker honoraria and/or travel compensation for activities with Bristol Myers Squibb, Novartis, Roche and research support of Baasch Medicus Foundation and the Swiss MS society, not related to this work. Andrew Chan has served on advisory boards for, and received funding for travel or speaker honoraria from Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche and Teva, all for hospital research funds; and research support from Biogen, Genzyme and UCB. Eric Twomey, Milo A. Puhan, Vladeta Ajdacic-Gross and Viktor von Wyl declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection., Design: Population based, longitudinal cohort., Setting: General population of canton of Zurich, Switzerland., Participants: 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection., Main Outcome Measures: Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection., Results: 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%))., Conclusions: Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials., Registrations: ISRCTN18181860, ., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/disclosure-of-interest(available on request from the corresponding author) and declare: funding for the research project by the Department of Health of the canton of Zurich, the University of Zurich Foundation and the Swiss Federal Office of Public Health; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. This study aimed to evaluate the prevalence and severity of post COVID-19 condition (PCC) with novel SARS-CoV-2 variants and after prior vaccination., Methods: We 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., Results: We found strong evidence that vaccinated individuals infected with Omicron had reduced odds of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The odds among non-vaccinated individuals were 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., Conclusion: The 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ballouz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Much remains unknown regarding the evolution of SARS-CoV-2 seroprevalence and variability in seropositive children in districts, schools and classes as only a few school-based cohort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to the understanding of how seroprevalence developed in the school aged population., Aim: We investigated the evolution of SARS-CoV-2 seroprevalence in children and its variability in districts, schools and classes in Switzerland from June/July 2020 to November/December 2021., Methods: In this school-based cohort study, SARS-CoV-2 antibodies were measured in primary and secondary school children from randomly selected schools in the canton of Zurich in October/November 2020, March/April 2021 and November/December 2021. Seroprevalence was estimated using Bayesian logistic regression to adjust for test sensitivity and specificity. Variability of seroprevalence between school classes was expressed as maximum minus minimum seroprevalence in a class and summarised as median (interquartile range)., Results: 1875 children from 287 classes in 43 schools were tested, with median age 12 years (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% credible interval [CrI] 3.5-7.6%) to 31.1% (95% CrI 27.0-36.1%) in unvaccinated children, and 46.4% (95% CrI 42.6-50.9%) in all children (including vaccinated). Earlier in the pandemic, seropositivity rates in primary schools were similar to or slightly higher (<5%) than those in secondary schools, but by late 2021, primary schools had 12.3% (44.3%) lower seroprevalence for unvaccinated (all) subjects. Variability in seroprevalence among districts and schools increased more than two-fold over time, and in classes from 11% (95% CrI 7-17%) to 40% (95% CrI 22-49%)., Conclusions: Seroprevalence in children increased greatly, especially in 2021 following introduction of vaccines. Variability in seroprevalence was high and increased substantially over time, suggesting complex transmission chains.

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID)., Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration., Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022., Exposures: Symptomatic SARS-CoV-2 infection., Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age., Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months., Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06-2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87-1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises., (© 2022. The Author(s).)

Objectives: To describe changes in adherence to recommendations for physical activity (PA), screen time (ST), and sleep duration over the first two waves of the pandemic in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health as well-being indicators. Methods: In this observational study, we included 2,534 participants (5-16 years) from four Swiss cantons. Participants, or their parents, completed repeated questionnaires and reported on their (child's) lifestyle and well-being, between June 2020 and April 2021. We used linear and logistic regression models to assess the associations between lifestyle and well-being. Results: The percentage of children meeting the recommendations for PA and ST decreased from the pre-pandemic period to the first wave, with a slight recovery during the second wave. Participants meeting all three recommendations during the second wave were more likely to report excellent health (OR: 1.65 [95% CI: 1.00-2.76]) and higher life satisfaction ( β : 0.46 [0.16-0.77]) in early 2021 than participants not meeting any recommendation. Conclusion: We showed a substantial impact of the COVID-19 pandemic on children's and adolescents' lifestyle, and a positive association between meeting lifestyle recommendations and well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peralta, Camerini, Haile, Kahlert, Lorthe, Marciano, Nussbaumer, Radtke, Ulyte, Puhan and Kriemler.)

Background: Long-term health consequences following acute SARS-CoV-2 infection, referred to as post-COVID-19 condition or Long COVID, are increasing, with population-based prevalence estimates for adults at around 20%. Persons affected by Long COVID report various health problems, yet evidence to guide clinical decision making remains scarce., Objective: The present study aimed to identify Long COVID research priorities using a citizen science approach and solely considering the needs of those affected., Methods: This citizen science study followed an iterative process of patient needs identification, evaluation and prioritisation. A Long COVID Citizen Science Board (21 persons with Long COVID, and seven with myalgic encephalomyelitis/chronic fatigue syndrome) and a Long COVID Working Group (25 persons with Long COVID, four patients with myalgic encephalomyelitis/chronic fatigue syndrome and one relative) were formed. The study included four activities: three remote meetings and one online survey. First, Board members identified the needs and research questions. Second, Working Group members and persons affected by Long COVID (241 respondents, 85.5% with Long COVID, 14.5% with myalgic encephalomyelitis/chronic fatigue syndrome and 7.1% relatives) evaluated the research questions on a 1-5 Likert scale using an online survey. Then the Board gave feedback on this evaluation. Finally, Board members set the priorities for research through voting and discussion., Results: Sixty-eight research questions were generated by the Board and categorised into four research domains (medicine, healthcare services, socioeconomics and burden of disease) and 14 subcategories. Their average importance ratings were moderate to high and varied from 3.41 (standard deviation = 1.16) for sex-specific diagnostics to 4.86 (standard deviation = 0.41) for medical questions on treatment. Five topics were prioritised: "treatment, rehabilitation and chronic care management", "availability of interfaces for treatment continuity", "availability of healthcare structures", "awareness and knowledge among professionals" and "prevalence of Long COVID in children and adolescents"., Conclusions: To our knowledge, this is the first study developing a citizen-driven, explicitly patient-centred research agenda with persons affected by Long COVID, setting it apart from existing multi-stakeholder efforts. The identified priorities could guide future research and funding allocation. Our methodology establishes a framework for citizen-driven research agendas, suitable for transfer to other diseases., (© 2022. The Author(s).)

Objective: To assess the associations between parents' working conditions during the lockdown period (March-May 2020) and children's health-related quality of life (HRQOL) over the first year of the COVID-19 pandemic in Zurich, Switzerland. Methods: We included 2211 children (6-16 years) and their parents from the prospective study Ciao Corona. Parents reported their employment status and working conditions during the lockdown. Children's HRQOL was assessed in June-July 2020, January and March 2021 using the parents-report of the KINDL®. We used mixed models to assess the associations between parents' working conditions and children's HRQOL at the three time points. Results: Children from families in which at least one parent changed their working conditions during the lockdown showed lower HRQOL in June-July 2020, than children from families in which neither parent experienced changes. Children from families in which at least one parent had to work remotely continued to show lower HRQOL in January and March 2021. Conclusion: Changes in parents' working conditions during lockdown were negatively associated with children's HRQOL. Public health policies aiming to support families susceptible to adverse changes are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muralitharan, Peralta, Haile, Radtke, Ulyte, Puhan and Kriemler.)

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection., (© 2022. The Author(s).)

Functional immunity (defined here as serum neutralising capacity) critically contributes to conferring protection against SARS-CoV-2 infection and severe COVID-19. This cross-sectional analysis of a prospective, population-based cohort study included 1,894 randomly-selected 16 to 99-year-old participants from two Swiss cantons in March 2022. Of these, 97.6% (95% CI: 96.8-98.2%) had anti-spike IgG antibodies, and neutralising capacity was respectively observed for 94%, 92% and 88% against wild-type SARS-CoV-2, Delta and Omicron variants. Studying functional immunity to inform and monitor vaccination campaigns is crucial.

Background: We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association., Methods: SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children <18 years of age (number, age group) and SARS-CoV-2 seropositivity. Further, we assessed the influence of reported non-household contacts, employment status, and gender., Results: Of 2393 working age participants (18-64 years), 413 (17.2%) were seropositive. Our results suggest that living with children and SARS-CoV-2 seropositivity are likely to be associated (unadjusted odds ratio (OR) 1.22, 95% confidence interval [0.98-1.52], adjusted OR 1.25 [0.99-1.58]). A pattern of a positive association was also found for subgroups of children aged 0-11 years (OR 1.21 [0.90-1.60]) and 12-17 years (OR 1.14 [0.78-1.64]). Odds of seropositivity were higher with more children (OR 1.14 per additional child [1.02-1.27]). Men had higher risk of SARS-CoV-2 infection when living with children than women (interaction: OR 1.74 [1.10-2.76])., Conclusions: In adults from the general population living with children seems associated with SARS-CoV-2 seropositivity. However, child-related infection risk is not the same for every subgroup and depends on factors like gender. Further factors determining child-related infection risk need to be identified and causal links investigated., Trial Registration: https://www.isrctn.com/ISRCTN18181860 ., (© 2022. The Author(s).)

Background: Few studies have directly examined the incidence or seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children, parents and teachers from the same school communities. This study aimed to describe SARS-CoV-2 seroprevalence within cantonal districts and school communities in children, parents and school personnel in June-September 2020 and March-April 2021 in the canton of Zürich, Switzerland., Methods: We invited children from 55 randomly selected primary and secondary schools and 275 classes within them to participate in the Ciao Corona study in June-July 2020. Parents of the participating children and all school personnel were invited in August-September 2020. Eligible classes, parents and school personnel were tested again in March-April 2021. Venous blood was tested for SARS-CoV-2 serology. We collected sociodemographic information of the participants in online questionnaires on enrolment in the study. We excluded vaccinated adults and those with unverified vaccination status from the main analysis. Seroprevalence estimates were adjusted for test accuracy. We assessed the variability of seroprevalence within and across cantonal districts and school communities and compared it with the per capita cumulative incidence of confirmed SARS-CoV-2 infections., Results: In June-September 2020, 2,473 children, 1,608 school personnel and 2,045 parents participated in the study. In June-September 2020, seroprevalence was low (4.4% to 5.8%) in all cohorts. In March-April 2021, seroprevalence in children and parents (18.1% and 20.9%) was slightly higher than in school personnel (16.9%). We observed a large variation in seroprevalence estimates of the three cohorts within and between districts and school communities, with the median ratio of children's seroprevalence to per capita confirmed cases in district inhabitants of 3.1 (interquartile range 2.6 to 3.9). Seroprevalence was lower in children in the upper school level and their parents, but not teachers. Children's seroprevalence was slightly higher in classes with infected main teachers and families with one infected parent and substantially higher in families with two infected parents., Conclusions: We observed similar seroprevalence in children and parents, somewhat lower in school personnel in March-April 2021 and striking variation between districts and school communities. Children's seroprevalence was higher in classes with infected main teachers and from families with infected parents.

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., (©Tala Ballouz, Dominik Menges, Hélène E Aschmann, Ruedi Jung, Anja Domenghino, Jan S Fehr, Milo A Puhan, Viktor von Wyl. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 19.05.2022.)

Background: Mask wearing contributes to the reduction of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Switzerland, compulsory use of masks was introduced in indoor public spaces and later in schools. This study explored perceptions of the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January to May 2021., Methods: School children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between 12 January and 24 March 2021 (Q1) and 10 March and 16 May 2021 (Q2). Secondary school children were surveyed at Q1 and Q2, and primary school children at Q2 only. Surveys for parents and their children included questions on the children's perception of the usefulness of masks and mask wearing behaviour by applying a non-validated questionnaire. Associations between perceived usefulness of masks and child's school level and gender, and parents' educational attainment were analysed with Pearson's and McNemar's chi-square tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing., Results: A total of 595 (54% girls) and 1118 (52% girls) school children with predominantly Swiss nationality and a high socioeconomic status responded to online questionnaires at Q1 and Q2, respectively. More than half of the school children perceived masks to be useful at school (Q1: 60% and Q2: 57%) and in public (Q1: 69% and Q2 :60%). Girls perceived masks as useful more often than boys (at Q2 at school: 61% versus 53%, in public: 64% versus 57%), and children of parents with high educational attainment more often than those of parents with lower educational attainment (at Q2 at school: 61% versus 49%, in public: 63% versus 54%). At Q1 and Q2 each, about 20% of children provided individual statements about masks, of which 36% at Q1 and 16% at Q2 reported side effects and discomfort such as skin irritations, headache or difficulties breathing during physical education., Conclusions: Approximately 60% of school children perceived masks at school and in public places as useful. A small but non-negligible proportion of children reported discomfort and side effects that should be considered to ensure high adherence to mask wearing among school children. A validation of the questionnaire is needed.

Background: Many studies in hospital settings exist and have shown healthcare employees to be particularly exposed to SARS-CoV-2. While research focused on hospital staff, little evidence exists for employees in nursing homes and home care. The aims of this study were to assess the seroprevalence in nursing homes and home care employees in the Canton of Zurich, compare it to the general population, assess factors associated with seropositivity and explore the perspective of the employees regarding how the pandemic changed their daily work., Methods: This cross-sectional study is part of the national Corona Immunitas research program of coordinated, seroprevalence studies in Switzerland. Six nursing homes and six home healthcare organizations providing at home care services in Zurich were selected and 296 and 131 employees were recruited, respectively. Assessments included standardized questionnaires, blood sampling for antibodies, and additional work-specific questions. All participants were recruited between 21st September and 23rd October 2020, before the second wave of the pandemic hit Switzerland, and were possibly exposed to SARS-CoV-2 at their work during the first wave in spring 2020., Results: Seroprevalence of SARS-CoV-2 was 14.9% (95% CI 11.1%-19.6%; range 3.8% to 24.4%) for nursing home employees and 3.8% (95% CI 1.4-9.1%; range 0% to 10%) for home healthcare employees, compared to the general population of Zurich at 3.5% in September 2020 for those aged 20-64. Nurses were 2.6 times more likely to have SARS-CoV-2 antibodies than those employees who were not nurses (95% CI 1.1-6.2). The employees (nursing homes vs. home healthcare) perceived the implementation of general safety measures (44.9% vs. 57.3%) and wearing masks during work (36.8% vs. 43.5%), especially due to the limited communication with residents/clients, as the most crucial changes., Conclusions: Nursing home employees who worked through SARS-CoV-2 outbreaks at their work were substantially more affected by SARS-CoV-2 infection compared to the general population and to home healthcare employees who similarly worked through outbreaks in their communities. Employees reported that important resources to cope with the burdensome changes they perceived in their daily work were personal resources and team support., Trial Registration: Current Controlled Trials ISRCTN18181860 dated 09/07/2020. Retrospectively registered., (© 2022. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Speierer, Chocano-Bedoya, Anker, Schmid, Keidel, Vermes, Imboden, Levati, Franscella, Corna, Amati, Harju, Luedi, Michel, Veys-Takeuchi, Zuppinger, Nusslé, D’Acremont, Tall, Salberg, Baysson, Lorthe, Pennacchio, Frei, Kaufmann, Geigges, West, Schwab, Cullati, Chiolero, Kahlert, Stringhini, Vollrath, Probst-Hensch, Rodondi, Puhan and von Wyl.)

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS., (© 2022. The Author(s).)

Background and Aims: Among people on opioid agonist treatment (OAT), social-environmental and behavioural risk factors may promote the spread of SARS-CoV-2, and somatic comorbidities are highly prevalent. Thus, this population is considered at elevated risk for being infected as well as for developing a more severe course of COVID-19 disease. The aim was to assess the SARS-CoV-2 seroprevalence among people in ongoing OAT, to explore whether the antibody positive group differed from the antibody negative group, and to compare the SARS-CoV-2 seroprevalence among OAT patients with the prevalence in the regional general population., Methods: The nationwide Corona Immunitas study assessed the participants' Sars-CoV-2 antibody status, social characteristics and behavioural data after the first wave of the corona pandemic in Switzerland, between the end of June and beginning of September 2020. We analysed the subsample of OAT patients (n = 122) and the subsample from the general population of the canton of Zurich (n = 472)., Results: SARS-CoV-2 seroprevalence in the general population (mean age ± standard deviation 44.7 ± 11.7 years; 50.9% female) was 3.5% (95% confidence interval [CI] 2.2-4.8%) vs 9.8% (5.1-17.2%) in the OAT population age 44.3 ± 9.4 years; 30.3% female), corresponding to a prevalence ratio of 2.9 (95% CI 1.37-5.94; p = 0.004). OAT patients had a significantly worse health status than the general population. In the OAT group, we found no significant difference between seropositive and seronegative individuals regarding socioeconomic status, risk behaviour, COVID-19-related symptoms or comorbidity. None of the OAT patients who tested positive had a severe course of COVID-19., Conclusion: The 3-fold higher seroprevalence suggests a higher than average viral exposure in the OAT group. Nevertheless, no severe COVID-19 course occurred, although the number of study participants was relatively small. One possible reason for this could be possible cross-immunity to SARS-CoV-2 due to frequent viral contacts in OAT patients.

Background: Few studies have explored the spread of SARS-CoV-2 in schools in 2021, with the advent of variants of concern. We aimed to examine the evolution of the proportion of seropositive children at schools from June-July 2020 to March-April 2021. We also examined symptoms, under-detection of infections, potential preventive effect of face masks, and reasons for non-participation in the study., Methods: Children in lower (7–10 years), middle (8–13 years) and upper (12–17 years) school levels in randomly selected schools and classes in the canton of Zurich, Switzerland, were invited to participate in the prospective cohort study Ciao Corona. Three testing rounds were completed in June-July 2020, October-November 2020 and March-April 2021. From 5230 invited, 2974 children from 275 classes in in 55 schools participated in at least one testing round. We measured SARS-CoV-2 serology in venous blood, and parents filled in questionnaires on sociodemographic information and symptoms., Results: The proportion of children seropositive for SARS-CoV-2 increased from 1.5% (95% credible interval [CrI] 0.6–2.6%) by June-July 2020, to 6.6% (4.0–8.9%) by October-November, and to 16.4% (12.1–19.5%) by March-April 2021. By March-April 2021, children in upper school level (12.4%; 7.3–16.7%) were less likely to be seropositive than those in middle (19.5%; 14.2–24.4%) or lower school levels (16.0%; 11.0–20.4%). The ratio of PCR-diagnosed to all seropositive children changed from one to 21.7 (by June-July 2020) to one to 3.5 (by March-April 2021). Potential clusters of three or more newly seropositive children were detected in 24 of 119 (20%) classes, 17 from which could be expected by chance. Clustering was not higher than expected by chance in middle and upper school levels. Children in the upper school level, who were wearing face masks at school from November 2020, had a 5.1% (95% confidence interval 9.4% to 0.7%) lower than expected seroprevalence by March-April 2021 than those in middle school level, based on difference-in-differences analysis. Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Fear of blood sampling (64%) was the most frequently reported reason for non-participation., Conclusions: Although the proportion of seropositive children increased from 1.5% in June-July 2020 to 16.4% in March-April 2021, few infections were likely associated with potential spread within schools. In March-April 2021, significant clustering of seropositive children within classes was observed only in the lower school level.

Objectives: We aimed to evaluate the effectiveness of the SwissCovid digital proximity tracing (DPT) app in notifying exposed individuals and prompting them to quarantine earlier compared to individuals notified only by manual contact tracing (MCT). Methods: A population-based sample of cases and close contacts from the Zurich SARS-CoV-2 Cohort was surveyed regarding SwissCovid app use and SARS-CoV-2 exposure. We descriptively analyzed app adherence and effectiveness, and evaluated its effects on the time between exposure and quarantine among contacts using stratified multivariable time-to-event analyses. Results: We included 393 SARS-CoV-2 infected cases and 261 close contacts. 62% of cases reported using SwissCovid and among those, 88% received and uploaded a notification code. 71% of close contacts were app users, of which 38% received a warning. Non-household contacts notified by SwissCovid started quarantine 1 day earlier and were more likely to quarantine earlier than those not warned by the app (HR 1.53, 95% CI 1.15-2.03). Conclusion: These findings provide evidence that DPT may reach exposed contacts faster than MCT, with earlier quarantine and potential interruption of SARS-CoV-2 transmission chains., Competing Interests: The Swiss School of Public Health (SSPH+) coordinates and performs fundraising for the overarching Corona Immunitas research program, of which the Zurich SARS-CoV-2 Cohort study is part. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ballouz, Menges, Aschmann, Domenghino, Fehr, Puhan and von Wyl.)

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., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This longitudinal cohort study aims to assess the extent and patterns of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in school-attending children, and their parents and school personnel. It will examine risk factors for infection, the relationship between seropositivity and symptoms, and temporal persistence of antibodies., Methods: The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5-16 years, attending primary and secondary schools, and their parents and school personnel are invited. Venous blood and saliva samples are collected for serological testing in June/July 2020, in October/November 2020, and in March/April 2021. Bi-monthly questionnaires will cover SARS-CoV-2 symptoms and tests, health, preventive behavior, and lifestyle information. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological tests in the analyses and complex sampling structure, i.e., clustering within classes and schools., Results and Conclusions: This unique school-based study will allow describing temporal trends of immunity, evaluate effects of preventive measures and will inform goal-oriented policy decisions during subsequent outbreaks. Trial registration ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/show/NCT04448717 .

Objectives: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community., Methods: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic., Results: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far., Conclusions: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .

ObjectiveTo evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection.DesignPopulation based, longitudinal cohort.SettingGeneral population of canton of Zurich, Switzerland.Participants1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection.Main outcome measuresTrajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection.Results22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)).ConclusionsUp to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials.RegistrationsISRCTN18181860, .

Genetic defects in the interferon (IFN) system or neutralizing autoantibodies against type I IFNs contribute to severe COVID-19. Such autoantibodies were proposed to affect post–COVID-19 syndrome (PCS), possibly causing persistent fatigue for >12 weeks after confirmed SARS-CoV-2 infection. In the current study, we investigated 128 patients with PCS, 21 survivors of severe COVID-19, and 38 individuals who were asymptomatic. We checked for autoantibodies against IFN-α, IFN-β, and IFN-ω. Few patients with PCS had autoantibodies against IFNs but with no neutralizing activity, indicating a limited role of type I IFNs in PCS pathogenesis. In a subset consisting of 28 patients with PCS, we evaluated IFN-stimulated gene activity and showed that it did not correlate with fatigue. In conclusion, impairment of the type I IFN system is unlikely responsible for adult PCS. [ABSTRACT FROM AUTHOR]

Background Seroprevalence and the proportion of people with neutralizing activity (functional immunity) against SARS-CoV-2 variants were high in early 2022. In this prospective, population- based, multi-region cohort study, we assessed the development of functional and hybrid immunity (induced by vaccination and infection) in the general population during this period of high incidence of infections with Omicron variants. Methods We randomly selected and assessed individuals aged ≥16 years from the general population in southern (n  = 739) and north-eastern (n  = 964) Switzerland in March 2022. We assessed them again in June/July 2022, supplemented with a random sample from western (n  = 850) Switzerland. We measured SARS-CoV-2 specific IgG antibodies and SARS-CoV-2 neutralizing antibodies against three variants (ancestral strain, Delta, Omicron). Results Seroprevalence remained stable from March 2022 (97.6%, n  = 1894) to June/July 2022 (98.4%, n  = 2553). In June/July, the percentage of individuals with neutralizing capacity against ancestral strain was 94.2%, against Delta 90.8% and against Omicron 84.9%, and 50.6% developed hybrid immunity. Individuals with hybrid immunity had highest median levels of anti-spike IgG antibodies titres [4518 World Health Organization units per millilitre (WHO U/mL)] compared with those with only vaccine- (4304 WHO U/mL) or infection- (269 WHO U/mL) induced immunity, and highest neutralization capacity against ancestral strain (hybrid: 99.8%, vaccinated: 98%, infected: 47.5%), Delta (hybrid: 99%, vaccinated: 92.2%, infected: 38.7%) and Omicron (hybrid: 96.4%, vaccinated: 79.5%, infected: 47.5%). Conclusions This first study on functional and hybrid immunity in the Swiss general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less so for the general population. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this scoping review was to map out the existing evidence of the impact of the COVID-19 lockdown on parents of children and adolescents. We sought to: 1) identify parenting domains that were particularly affected by lockdown measures, 2) describe the challenges and opportunities of lockdown measures in these domains, and 3) define protective and exacerbating factors modulating the effect of lockdown measures on parents. Methods: We identified five main domains investigated in the context of parenting during the early COVID-19 lockdown derived from 84 studies: health and wellbeing, parental role, couple functioning, family and social relationships, and paid and unpaid work. For each domain, we listed challenges and opportunities, as well as discriminant factors. Results: The lockdown impacted all five different but interconnected domains, introduced new roles in parents' lives, and particularly affected women and vulnerable populations. Conclusion: This scoping review highlights the importance of approaching public health policymaking from a social justice perspective. Such an approach argues for social and public health policies to promote health accounting for its social, economic, political, and commercial determinants. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 infection can impact the central nervous system, and is often associated with cognitive decline. However, there are no studies linking serologically confirmed COVID-19 infection with objectively assessed cognitive functioning. We explored whether presence of SARS-CoV-2 antibodies account for variability in participants’ scores on a neuropsychological assessment. Methods: In this cross-sectional study participants were 657 (mean age = 72.97; SD = 6.07 years; women = 47.7%) individuals randomly selected from the general population of the canton of Zurich and included in the Corona Immunitas study. We conducted serological tests between October 2020 and May 2021 to detect and quantify SARS-CoV-2 antibodies in peripheral venous blood samples. We assessed cognitive function, vaccination status (vaccinated; not vaccinated), number of health conditions, and demographic variables between January and August 2021. We studied the association between seropositivity and global cognitive function and five cognitive domains (language expression, language comprehension, temporal orientation, spatial orientation, and memory) with linear regression models. Based on SARS-CoV-2 antibodies and vaccination status, we stratified participants into three groups: No SARS-CoV-2 antibodies (N = 402); SARS-CoV-2 antibodies due to vaccination (N = 218); history of SARS-CoV-2 infection and no vaccination (N = 37). Results: In the regression model adjusted for age, sex, educational level, and number of health conditions, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to vaccination had better global cognitive functioning (Standardized beta = 0.10; 95% CI = 0.02; 0.17), and those with SARS-CoV-2 antibodies due to infection had poorer cognitive functioning (Standardized beta = −0.10; 95% CI = −0.18; −0.03). Regarding cognitive domains, compared to those without SARSCoV-2 antibodies, those with SARS-CoV-2 antibodies due to infection scored more poorly on language comprehension and temporal orientation, and those with SARSCoV-2 antibodies due to vaccination scored better on memory. Discussion: By linking serologically confirmed presence of SARS-CoV-2 antibodies to poorer global cognitive functioning in community dwelling older adults we strengthen existing evidence in support of cognitive decline related to COVID-19. Given the large number of infected older adults, and the endurance of the pandemic, our results highlight the need to address COVID-19 related cognitive decline in the clinical and public health areas of prevention, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Multiplexing SARS-CoV-2 neutralization: Neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are primarily assessed using cell-based assays requiring live virus. These assays are time-consuming and necessitate that additional biosafety precautions be taken, thus limiting their clinical use. Here, Fenwick et al. developed a cell-free surrogate neutralization assay to quantify neutralizing antibody responses. In this assay, neutralizing antibodies block the ability of fluorescent angiotensin-converting enzyme 2 (ACE2) molecules from binding to recombinant SARS-CoV-2 spike protein trimers. The assay achieved 96.7% sensitivity and 100% specificity in comparison to a gold standard, cell-based assay and could be multiplexed to quantify responses against SARS-CoV-2 variants of concern in one test. The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies in the serum of an individual indicates previous infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific immunoglobulin G titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the β (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Public health interventions implemented during the coronavirus disease 2019 (COVID-19) pandemic are based on experience gained from past pandemics. The 1918 influenza pandemic is the most extensively researched historical influenza outbreak. All 9335 reports available in the State Archives on 121 152 cases of influenza-like illness from the canton of Bern from 473 of 497 municipalities (95.2%) were collected; the cases were registered between 30 June 1918 and 30 June 1919. The overall incidence rates of newly registered cases per week for the 9 greater regions of Bern for both the first and second waves of the pandemic were calculated. Relative incidence rate ratios (RIRRs) were calculated to estimate the change in the slope of incidence curves associated with public health interventions. During the first wave, school closures (RIRR, 0.16 [95% CI, 0.15 to 0.17]) and restrictions of mass gatherings (RIRR, 0.57 [CI, 0.54 to 0.61]) were associated with a deceleration of epidemic growth. During the second wave, in autumn 1918, cantonal authorities initially reacted hesitantly and delegated the responsibility to enact interventions to municipal authorities, which was associated with a lack of containment of the second wave. A premature relaxation of restrictions on mass gatherings was associated with a resurgence of the epidemic (RIRR, 1.18 [CI, 1.12 to 1.25]). Strikingly similar patterns were found in the management of the COVID-19 outbreak in Switzerland, with a considerably higher amplitude and prolonged duration of the second wave and much higher associated rates of hospitalization and mortality. [ABSTRACT FROM AUTHOR]