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BackgroundSeroprevalence and the proportion of people with neutralizing activity against SARS-CoV-2 variants was high in early 2022. Since it is unclear how immunity in the general population evolves, the aim of this study was to assess the development of functional and hybrid immunity in the general population during a period of high incidence of infections with Omicron variants. MethodsThis prospective population based multi-region cohort study is part of the Corona Immunitas research programme in Switzerland. In March 2022, we randomly selected individuals from the general population in southern (canton of Ticino) and north-eastern (canton of Zurich) Switzerland, who were assessed again in June/July 2022. We supplemented the June/July 2022 sample with a random sample from western Switzerland (canton of Vaud). We assessed SARS-CoV-2 specific IgG antibodies against spike and nucleocapsid proteins and the presence of SARS-CoV-2 neutralising antibodies against three variants (wildtype, Delta, Omicron). FindingsIn June/July 2022, seroprevalence was >98% in 2553 individuals from the general Swiss population. The proportion of individuals with neutralising antibodies against wildtype, Delta, and Omicron was 94.2%, 90.8%, and 84.9%, and at least 51% of the participants developed hybrid immunity. Individuals with hybrid immunity had, compared to those with only vaccine- or infection-induced immunity, highest levels of both, anti-spike IgG antibodies titres (4518 vs. 4304 vs. 269 WHO U/ml) and neutralisation capacity against wildtype (99.8% vs. 98% vs. 47.5%), Delta (99% vs. 92.2% vs. 38.7%), and Omicron (96.4% vs. 79.5% vs. 47.5%). InterpretationThis first study on functional and hybrid immunity in the general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization in the general populations support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less strongly recommended for individuals in the general population. FundingThe Corona Immunitas research network is coordinated by the Swiss School of Public Health (SSPH+) and funded by fundraising of SSPH+ including funds of the Swiss Federal Office of Public Health and private funders (ethical guidelines for funding stated by SSPH+ were respected), by funds of the cantons of Switzerland (Vaud, Zurich, and Basel), and by institutional funds of the Universities. Study registrationISRCTN18181860 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed, Medline, Scopus and Web of Knowledge, for primary population-based studies prospectively assessing infection-, vaccine-induced, and hybrid immunity and the respective neutralising activity of antibodies against SARS-CoV-2 and its variants of concern. We included articles published between 1 January and 28 September 2022, without language restrictions, and retrieved 540 publications after deduplication. None of the screened studies measured the prevalence of immune response and neutralisation capacity prospectively in population-based, representative samples accounting for type of acquired immunity. Evidence from five studies, all conducted in non-representative, convenience and relatively small samples (N<254), and/or in sub-populations (e.g., healthcare workers and children), shows that hybrid immunity confers higher immune protection and exhibits better neutralising capacity compared to vaccine- and infection-induced immunity. Furthermore, one of the screened studies highlights that antibodies developed by individuals with hybrid immunity show the slowest decline over a period of 10 months. Added value of this studyWe took advantage of an ongoing cohort study on anti-SARS-CoV-2 seroprevalence conducted in a representative sample of the general Swiss population (N=2553) using standard, previously validated methods, to measure changes over time in seroprevalence, neutralisation capacity against wildtype and variants of concerns of the virus (i.e., ACE2r-block), waning of antibodies, and new infections. This is the first study, conducted in the general population and during the pandemic phase characterized by very high incidence of Omicron infections, to assess the extent of hybrid immunity (51%) and neutralising antibodies against the wildtype (94.2%), Delta (90.8%), and Omicron variants (84.9%). Our findings show that individuals with hybrid immunity, compared to those with only vaccine- or infection-induced immunity, had the highest levels of both anti-spike IgG antibodies titres and neutralisation capacity against wildtype, Delta, and Omicron variants. We also found that, from March to June/July 2022, anti-spike IgG antibodies remained stable in the general population (>96%), while anti-nucleocapsid IgG antibodies fluctuated due to their fast waning (7.3% of participants anti-nucleocapsid IgG antibodies became undetectable) and the parallel spread of Omicron infections (18.6% of participants acquired anti-nucleocapsid IgG antibodies). Implications of all the available evidenceBy mid-2022, SARS-CoV-2 has become endemic, and a majority of individuals developed hybrid immunity with high levels of neutralisation against the wildtype, Delta, and Omicron variants of SARS-CoV-2. Combined with existing evidence, our results indicate that hybrid immunity confers higher levels of neutralising activity compared to both vaccine-induced and infection-induced immunity. This study extends findings on the immunological protection conferred by hybrid immunity from sub-populations to the general population. The high levels of antibodies and neutralization in the general populations support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less strongly recommended for individuals in the general population. Monitoring the prevalence, waning, and neutralising activity of antibodies against potential new variants of concern in populations remains crucial.
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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.
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BackgroundEvidence 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. ObjectivesTo evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. DesignPopulation-based, longitudinal cohort. SettingGeneral population, Canton of Zurich, Switzerland. Patients1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. MeasurementsChanges 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. Results25% 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. LimitationsWe relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. ConclusionThese 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.
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BackgroundMuch 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 co-hort studies exist. Vaccination of children, initiated at different times for different age groups, adds additional complexity to understand how seroprevalence developed in the school aged population. AimWe 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. MethodsIn 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 sero-prevalence in a class and summarized as median (interquartile range). Results1875 children from 287 classes in 43 schools were tested, with median age 12 (range 6-17), 51% 12+ vaccinated. Seroprevalence increased from 5.6% (95% CrI: 3.5-7.6%) to 31.1% (27.0-36.1%) in unvaccinated children, and 46.4% (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 twofold over time, and in classes from 11% (7-17%) to 40% (22-49%). ConclusionSeroprevalence 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. Trial Registration: ClinicalTrials.gov NCT04448717
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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.
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We measured SARS-CoV-2 seroprevalence in cohorts of children, parents and school personnel in 55 randomly selected schools in the canton of Zurich, Switzerland. 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%). Childrens 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.
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To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses. One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.
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BackgroundPrevious studies assessing the impact of the COVID-19 pandemic on childrens and adolescents lifestyle focused mainly on the first wave in early 2020. We aimed 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 (March-May 2020 and October 2020-January 2021) in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health, as indicators of well-being. MethodsWe included 3168 participants aged 5 to 18 years from four Swiss cantons. Participants or their parents completed repeated questionnaires and reported on their (childs) PA, ST, sleep, life satisfaction, and overall health. We analysed lifestyle behaviours in terms of adherence to international recommendations. We used linear and logistic regression models to assess the associations of number of recommendations met and adherence patterns with well-being indicators. FindingsCompared to the pre-pandemic period, the percentage of participants meeting the recommendations for PA and ST decreased strikingly during March-May 2020, while there was a slight increase in those meeting recommendations for sleep. During October 2020-January 2021, the percentage of compliant children for PA and ST increased but remained lower than before the pandemic. Participants meeting all three recommendations were more likely to report excellent health (OR: 1{middle dot}87 [1{middle dot}15-3{middle dot}08]) and a higher life satisfaction score ({beta}: 0{middle dot}59 [0{middle dot}30-0{middle dot}88]) than participants not meeting any recommendation. Adherence to recommendations for PA and sleep, PA and ST, and sleep and ST was similarly associated with both well-being indicators. InterpretationWe show a substantial impact of the COVID-19 pandemic on childrens and adolescents lifestyle behaviours with a partial recovery over time, and an association between lifestyle and well-being. Public health policies to promote childrens and adolescents well-being should target PA, ST, and sleep simultaneously. FundingCorona Immunitas. RESEARCH IN CONTEXTO_ST_ABSEvidence before the studyC_ST_ABSWe searched PubMed for studies assessing the effects of the COVID-19 pandemic on childrens and adolescents lifestyle behaviours, published up to September 6, 2021, with no language restrictions. Of the studies found, nearly all compared lifestyle behaviours before and during the strict confinement in the first wave of the pandemic, and very few studies extended their assessment beyond June 2020. The only longitudinal study assessing lifestyle changes up to 2021 included a sample of nineteen boys. Some studies assessed the association between lifestyle behaviours and well-being after the outbreak of the pandemic, but all used a single-behaviour approach (i.e., evaluated only one lifestyle behaviour) and no study considered the combined contribution of physical activity (PA), screen time (ST), and sleep. In addition, most studies were cross-sectional and did not consider pre-pandemic lifestyle behaviours. Added value of this studyThis is the first study assessing changes in adherence to international recommendations regarding PA, ST, and sleep duration in children and adolescents during the first two waves of the COVID-19 pandemic and the joint associations of these lifestyle behaviours with well-being. We used data from 3168 children and adolescents from four different Swiss cantons. We included measurements of PA, ST, and sleep before the pandemic, during the first wave between March and May 2020, and during the second wave between October 2020 and January 2021. We also assessed life satisfaction and overall health as indicators of well-being, between January and April 2021. We showed that, compared to the pre-pandemic period, the proportion of children and adolescents following the recommendations for PA and ST decreased during the first wave (lockdown period), while there was a slight increase in those meeting recommendations for sleep. During the second wave, the prevalence of compliant children and adolescents for PA and ST recovered but remained below pre-pandemic levels. Furthermore, we found an association between the number of recommendations met for lifestyle behaviours during the second wave and well-being assessed between January and April 2021. In contrast, there was no such association for the periods before the pandemic or during the lockdown. Participants following the recommendations for all three lifestyle behaviours or for combinations of two of them in the second wave were more likely to report excellent health and had a higher life satisfaction score, than those not meeting any recommendation. Implications of all the available evidenceOur findings demonstrate that the COVID-19 pandemic has had a strong negative effect on childrens and adolescents lifestyle behaviours, but some recovery has taken place within the first year since the outbreak. Policymakers should imperatively consider the balance of disease prevention and promotion of a healthy lifestyle when (re-)activating restrictive measures. Given the already high prevalence of children and adolescents not meeting lifestyle recommendations in the pre-pandemic period, our findings highlight the urgent need for public health policies aiming to avoid permanent negative changes on childrens and adolescents lifestyle and to mitigate the health risks associated with adverse changes during the pandemic. In addition, our study indicates that lifestyle is an important predictor of childrens and adolescents well-being, and it further suggests that future public health strategies aiming to promote well-being should target sufficient time for PA and sleep as well as reduce ST.
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BackgroundMask 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. In the canton of Zurich, masks were introduced for secondary school children (grades 7-9) from November 2020, and for primary school children (grades 4-6) from February 2021- along with other protective measures against SARS-CoV-2. This study explored perceptions towards the usefulness of masks in school and public in a cohort of children and adolescents in the canton of Zurich, Switzerland, in January - May 2021. MethodsSchool children aged 10 to 17 years enrolled in Ciao Corona, a prospective school-based cohort study, responded to nested online surveys between January 12 to March 24 2021 (Q1) and March 10 to May 16 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 childrens perception of the usefulness of masks and mask wearing behavior. Associations between perceived usefulness of masks and childs school level, gender, and parents educational attainment were analyzed with Pearsons and McNemars chi-squared tests. Free-text comments provided by children were classified into categories of expressed attitude towards mask wearing. Results595 (54% girls) and 1118 (52% girls) school children responded to online questionnaires at Q1 and Q2, respectively. More than half of 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%). There were no differences in the perceived usefulness of masks among children in primary versus secondary school. 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. ConclusionApproximately 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. Trial registrationClinicalTrials.gov NCT04448717 https://clinicaltrials.gov/ct2/show/NCT04448717 CONTRIBUTION TO THE FIELD STATEMENTWorldwide about 150 countries fully closed their schools at some point during the coronavirus pandemic, while other countries - such as Switzerland - kept schools open almost all the time. However, among other protective measures, children in secondary school (aged approximately 14-16 years) had to wear masks since November 2020, and older children in primary school (aged 11-13 years) - since February 2021. As part of the large study Ciao Corona based in schools in Switzerland, we wanted to learn how children perceive the usefulness of masks in school and public. Children and their parents completed questionnaires in January-March (595 secondary school children) and March-May 2021 (1118 secondary and primary school children). We found that about 60% of children perceived masks to be useful at school and in public. Girls perceived masks as useful more often than boys, and children of parents with university or college education more often than those of parents with lower education. About 7- 9% of children reported side-effects and discomfort such as skin irritations, headache or difficulties breathing during physical education. Although side-effects were not frequently reported, they should be considered to ensure high adherence to mask wearing among school children.
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ObjectivesTo longitudinally assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and clustering of seropositive children within school classes in March-April 2021 compared to June-July and October-November 2020. To examine the evolution of symptoms and the extent of under-detection of SARS-CoV-2 in children. DesignProspective cohort study of randomly selected schools and classes. SettingSchools remained open for physical attendance in Switzerland from May 2020 to the end of 2020/2021 school year. Lower school level (age range 7-10 years) and middle school level (8-13 years) children in primary schools, and upper school level (12-17 years) children in secondary schools were invited for SARS-CoV-2 serological testing in the Ciao Corona study in the canton of Zurich, Switzerland. Three testing rounds were completed in June-July 2020 (T1; after the first wave of SARS-CoV-2 infections), October-November 2020 (T2; during the peak of the second wave), and March-April 2021 (T3; after the second wave and with SARS-CoV-2 variants of concern becoming dominant). Parents completed questionnaires on sociodemographic information and symptoms. Participants2487 children (median age 12 years, age range 7-17 years) recruited from 275 classes in 55 schools participated in the testing in March-April 2021; total of 2974 children participated in at least one of the 3 testing rounds. Main outcome measuresSARS-CoV-2 serology results; clustering of seropositive children within classes; reported symptoms. ResultsThe proportion of children who were SARS-CoV-2 seropositive increased from 1.5% (95% credible interval (CrI) 0.6% to 2.6%) in June-July 2020, to 6.6% (95% CrI 4.0% to 8.9%) in October-November, and to 16.4% (95% CrI 12.1% to 19.5%) in March-April 2021. By March-April 2021, children in upper school level (12.4%; 95% CrI 7.3% to 16.7%) were less likely to be seropositive than those in middle (19.5%; 95% CrI 14.2% to 24.4%) or lower school levels (16.0%; 95% CrI 11.0% to 20.4%). Children in the upper school level had a 5.1% (95% CI -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. The ratio of PCR-diagnosed to all seropositive children changed from 1 to 21.7 (by June-July 2020) to 1 to 3.5 (by March-April 2021). Symptoms were reported by 37% of newly seropositive and 16% seronegative children. Potential clusters of 3 or more newly seropositive children were detected in 24 of 119 (20%) classes with a high participation rate, from which a median of 17 clusters could be expected due to random distribution of seropositive children within the classes. Clustering was lowest in middle and upper school levels. Retention rate in the cohort was high (84% of T1 participants attended T3). Among participants, supporting society and research were reported more commonly for participation than personal reasons. Fear of blood sampling was the most frequently reported reason for non-participation, reported for 64% of children. ConclusionsBy March-April 2021, 16.4% of children and adolescents were seropositive in the canton of Zurich, Switzerland. The majority of clusters of SARS-CoV-2 seropositive children in school classes could be explained by community rather than intra-class transmission of infections. Seroprevalence and clustering was lowest in upper school levels during all timepoints. Trial registrationClinicalTrials.gov NCT04448717. What is already known on the topicO_LITransmission of SARS-CoV-2 in school setting largely followed community transmission in 2020. C_LIO_LIWith implemented preventive measures, secondary attack rates were low and clustering of SARS-CoV-2 infections within classes and schools (outbreaks) were observed rarely. C_LI What this study addsO_LIWith high community incidence and new variants of SARS-CoV-2, seroprevalence increased in school children between October 2020 - March 2021 in the canton of Zurich in Switzerland, and was higher in lower school levels. C_LIO_LIMost of the potential clusters of children who tested seropositive within classes could be explained by community rather than intra-class transmission of SARS-CoV-2, especially in middle and upper school levels. C_LIO_LIMore children who tested seropositive in March-April 2021 were diagnosed and reported symptoms potentially related to SARS-CoV-2 infection more frequently than those who tested seropositive in June-July or October-November 2020. C_LIO_LIThe most frequent reason for non-participation was fear of blood sampling (62% of children). C_LI
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BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization. MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes. ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care. ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care. RegistrationISRCTN14990068
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BackgroundSwitzerland had one of the highest incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Europe during the second wave. Schools were open as in most of Europe with specific preventive measures in place. However, the frequency and transmission of acute unrecognized, asymptomatic or oligosymptomatic infections in schools during this time of high community transmission is unknown. Thereof, our aim was to pilot a surveillance system that detects acute SARS-CoV-2 infections in schools and possible transmission within classes. Methods14 out of the randomly selected sample of the Ciao Corona cohort study participated between December 1 and 11, a time when incidence rate for SARS-CoV-2 infections was high for the canton of Zurich. We determined point-prevalence of acute SARS-CoV-2 infections of school children attending primary and secondary school. A buccal swab for polymerase chain reaction (PCR) and a rapid diagnostic test (RDT) to detect SARS-CoV-2 were taken twice 1 week apart (T1 and T2) in a cohort of children from randomly selected classes. A questionnaire assessed demographics and symptoms compatible with a SARS-CoV-2 infection during the past 5 days. ResultsOut of 1299 invited children, 641 (49%) 6- to 16-year-old children and 66 teachers from 14 schools and 67 classes participated in at least 1 of 2 testings. None of the teachers but 1 child had a positive PCR at T1, corresponding to a point-prevalence in children of 0.2% (95% CI 0.0% to 1.1%), and no positive PCR was detected at T2. The child with positive PCR at T1 was negative on the RDT at T1 and both tests were negative at T2. There were 7 (0.6%) false positive RDTs in children and 2 (1.7%) false positive RDTs in teachers at T1 or T2 among 5 schools (overall prevalence 0.7%). All 9 initially positive RDTs were negative in a new buccal sample taken 2 hours to 2 days later, also confirmed by PCR. 35% of children and 8% of teachers reported mild symptoms during the 5 days prior to testing. ConclusionIn a setting of high incidence of SARS-CoV-2 infections, unrecognized virus spread within schools was very low. Schools appear to be safe with the protective measures in place (e.g., clearly symptomatic children have to stay at home, prompt contact tracing with individual and class-level quarantine, and structured infection prevention measures in school). Specificity of the RDT was within the lower boundary of performance and needs further evaluation for its use in schools. Given the low point prevalence even in a setting of very high incidence, a targeted test, track, isolate and quarantine (TTIQ) strategy for symptomatic children and school personnel adapted to school settings is likely more suitable approach than surveillance on entire classes and schools. Trial registrationClinicalTrials.gov NCT04448717 https://clinicaltrials.gov/ct2/show/NCT04448717
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BackgroundDigital proximity tracing (DPT) apps may warn exposed individuals faster than manual contact tracing (MCT), leading to earlier interruption of transmission chains through quarantine. However, it is yet unclear whether these apps lead to a reduction in transmissions under real-world conditions. This study aimed at evaluating whether the SwissCovid DPT app is effective in warning close contacts of SARS-CoV-2 infected cases and prompting them to quarantine earlier. MethodsA population-based sample of adult index cases and close contacts identified through MCT and enrolled in the Zurich SARS-CoV-2 Cohort study were surveyed regarding use of the SwissCovid app and SARS-CoV-2 exposure setting. We analyzed ooutcomes related to app effectiveness and adherence (i.e., receipt and uploading of notification codes by index cases; receipt of app warnings and steps taken by close contacts). Furthermore, we performed adjusted time-to-event analyses stratified by exposure setting to estimate the effect of the app on time between relevant exposure and entering quarantine among close contacts. FindingsWe included 393 index cases and 261 close contacts in the analysis. Among index cases using SwissCovid, 88% reported receiving and uploading a notification code in the app to trigger a warning among proximity contacts. Among close contacts using the app, 38% reported receiving an app warning due to the risk exposure. We found that non-household contacts who were notified by the app started quarantine at a median of 2 days after exposure, while those not notified started quarantine at a median of 3 days. In stratified multivariable analyses, app notified contacts had a greater probability of going into quarantine earlier than those without app notification (HR 1{middle dot}53, 95% CI 1{middle dot}15-2{middle dot}03). InterpretationOur study showed that non-household contacts notified by the app started quarantine one day earlier than those not notified by the app. These findings constitute the first evidence that DPT may reach exposed contacts faster than MCT, leading to earlier quarantine and potential interruption of SARS-CoV-2 transmission chains. FundingCantonal Health Directorate Zurich, University of Zurich Foundation and the Swiss Federal Office of Public Health.
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Background and aimsThe facilitating role of schools in SARS-CoV-2 infection spread is still debated and the potential of school closures to mitigate transmission unclear. In autumn 2020, Switzerland experienced one of the highest second waves of the SARS-CoV-2 pandemic in Europe while keeping schools open, thus offering a high-exposure environment to study SARS-CoV-2 infections in schools. The aim of this study was to examine longitudinal change in SARS-CoV-2 seroprevalence in children and the evolution of clustering within classes and schools from June to November, 2020, in a prospective cohort study of school children in the canton of Zurich, Switzerland. MethodsChildren from randomly selected schools and classes, stratified by district, were invited to participate in serological testing of SARS-CoV-2 in June-July and October-November 2020. Parents of children filled questionnaires on sociodemographic and health-related questions. 55 schools and 275 classes within them were enrolled, with 2603 children participating in the first, and 2552 in the second testing (age range 6-16 years). We evaluated longitudinal changes of seroprevalence in districts and investigated clustering of seropositive cases within classes and schools. ResultsOverall SARS-CoV-2 seroprevalence was 2.4% (95% CrI 1.4%-3.6%) in summer and 4.5% (95% CrI 3.2%-6.0%) in not previously seropositive children in late autumn, leading to estimated 7.8% (95% CrI 6.2%-9.5%) of ever seropositive children, without significant differences among lower, middle and upper school levels. Among the 2223 children with serology tested twice, 28 (40%) of previously seropositive were negative, and 109 (5%) previously negative became seropositive. Seroprevalence was not different between school levels or sexes, but varied across districts (1.7% to 15.0%). Between June-July and October-November 2020, the ratio of diagnosed to newly seropositive children was 1 to 8. At least one newly seropositive child was detected in 47 of 55 schools and 90 of 275 classes. Among 130 classes with high participation rate, 0, 1-2 or [≥]3 seropositive children were present in 73 (56%), 50 (38%) and 7 (5%) classes, respectively. Class level explained slightly more variation of individual serological results (standard deviation of random effects (SD) 0.97) than school level (SD 0.61) in the multilevel logistic regression models. Symptoms were reported for 22% of seronegative and 29% of newly seropositive children since summer. ConclusionsUnder a regimen of open schools with some preventive measures in place since August, clustering of seropositive cases occurred in very few classes and not across entire schools despite a clear increase in seropositive children during a period of high transmission of SARS-CoV-2. Trial registrationClinicalTrials.gov NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717
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Importance: Understanding transmission and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in school children is critical to implement appropriate mitigation measures. Objective: To determine the variation in SARS-CoV-2 seroprevalence in school children across districts, schools, grades, and classes, and the relationship of SARS-CoV-2 seroprevalence with self-reported symptoms. Design: Cross-sectional analysis of baseline measurements of a longitudinal cohort study (Ciao Corona) from June-July 2020. Setting: 55 randomly selected schools and classes stratified by district in the canton of Zurich, Switzerland (1.5 million inhabitants). Participants: Children, aged 6-16 years old, attending grades 1-2, 4-5 and 7-8. Exposure: Exposure to circulating SARS-CoV-2 between February and June 2020 including public lock-down and school closure (March 16-May 10, 2020). Main Outcomes and Measures: Variation in seroprevalence of SARS-CoV-2 in children across 12 cantonal districts, schools, and grades using a Luminex-based antibody test with four targets for each of IgG, IgA and IgM. Clustering of cases within classes. Analysis of associations of seropositivity and symptoms. Comparison of seroprevalence with a randomly selected adult population, based on Luminex-based IgG and IgA antibody test of Corona Immunitas. Results: In total, 55 schools and 2585 children were recruited (1337 girls, median age 11, age range 6-16 years). Overall seroprevalence was 2.8 % (95% CI 1.6-4.1%), ranging from 1.0% to 4.5% across districts. Seroprevalence was 3.8% (1.9-6.1%) in grades 1-2, 2.5% (1.1-4.2%) in grades 4-5, and 1.5% (0.5-3.0%) in grades 7-8. At least one case was present in 36/55 tested schools and in 43/128 classes with [≥]50% participation rate and [≥]5 children tested. 73% of children reported COVID-19 compatible symptoms since January 2020, but none were reported more frequently in seropositive compared to seronegative children. Seroprevalence of children was very similar to seroprevalence of randomly selected adults in the same region in June-July 2020, measured with the same Corona Immunitas test, combining IgG and IgA (3.1%, 95% CI 1.4-5.4%, versus 3.3%, 95% CI 1.4-5.5%). Conclusions and Relevance: Seroprevalence was inversely related to age and revealed a dark figure of around 90 when compared to 0.03% confirmed PCR+ cases in children in the same area by end of June. We did not find clustering of SARS-CoV-2 seropositive cases in schools so far, but the follow-up of this school-based study will shed more light on transmission within and outside schools. Trial registration: ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/show/NCT04448717
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IntroductionSeroprevalence and transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents, especially in school setting, are not clear. Resulting uncertainty is reflected in very different decisions on school closures and reopenings across countries. The aim of this longitudinal cohort study is to assess the extent and patterns of seroprevalence of SARS-CoV-2 antibodies in school-attending children repeatedly. It will examine risk factors for infection, relationship between seropositivity and symptoms, and temporal persistence of antibodies. Additionally, it will include testing of school personnel and parents. Methods and analysisThe 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 to 16 years, attending classes in primary and secondary schools are invited. Venous blood and saliva samples are collected for SARS-CoV-2 serological testing after the first wave of infections (June/July 2020), in fall (October/November 2020), and after winter (March/April 2021). Venous blood is also collected for serological testing of parents and school personnel. Bi-monthly questionnaires to children, parents and school personnel cover SARS-CoV-2 symptoms and tests, health, preventive behavior, lifestyle and quality of life information. Total seroprevalence and cumulative incidence will be calculated. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological test in the analyses and for the complex sampling structure, i.e., clustering within classes and schools. Ethics and disseminationThe study was approved by the Ethics Committee of the Canton of Zurich, Switzerland (2020-01336). The results of this study will be published in peer-reviewed journals and will be made available to study participants and participating schools, the Federal Office of Public Health, and the Educational Department of the canton of Zurich. Trial registration number NCT04448717. O_LICiao Corona is a large, prospective school-based cohort study and will provide robust data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, transmission routes and immunity over time in a representative sample of school children. C_LIO_LIThe longitudinal design will allow describing temporal trends of immunity to SARS-CoV-2 infection and to evaluate effects of school structure and preventive measures. C_LIO_LIThis study will inform goal-oriented policy decisions in school management during subsequent outbreaks. C_LIO_LIParticipation bias, missing questionnaires, desirability bias, and loss of follow up may occur. The validity of serological tests may also hamper results. C_LI
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Effective public-health measures and vaccination campaigns against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against the ectodomain and the receptor-binding domain of the spike protein as well as the nucleocapsid protein of SARS-CoV-2. We used TRABI for continuous seromonitoring of hospital patients and healthy blood donors (n=72222) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). Seroprevalence peaked in May 2020 and rose again in November 2020 in both cohorts. Validations of results included antibody diffusional sizing and Western Blotting. Using an extended Susceptible-Exposed-Infectious-Removed model, we found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020 in the population of the canton of Zurich. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19 and up to the timepoint of survey participation. Crucially, we found no evidence for a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2- infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.