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1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22283400

RESUMEN

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of commercially available high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. In this work, we leverage repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, to evaluate anti-Spike RBD antibody levels as a correlate of protection against Omicron BA.1/BA.2 infections during the December 2021-March 2022 epidemic wave. We do so by first modeling antibody dynamics in time with kinetic models. We then use these models to predict antibody trajectories into the time period where Omicron BA.1/BA.2 were the predominant circulating sub-lineages and use survival analyses to compare the hazard of having a positive SARS-CoV-2 test by antibody level, vaccination status and infection history. We find that antibody kinetics in our sample are mainly determined by infection and vaccination history, and to a lesser extent by demographics. After controlling for age and previous infections (based on anti-nucleocapsid serology), survival analyses reveal a significant reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave with increasing antibody levels, reaching up to a three-fold reduction for anti-S antibody vels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a eduction in hazard among uninfected participants. Taken together these results indicate that nti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an direct correlate of protection against Omicron BA.1/BA.2 for individuals with a history of revious SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will me next, these results provide reassuring insights into the continued interpretation of ARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

2.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22282491

RESUMEN

BackgroundThe medium-term impact of the COVID-19 pandemic on the wellbeing of children and adolescents remains unclear. More than two years into the pandemic, we aimed to quantify the frequency and determinants of having been severely impacted by the COVID-19 pandemic and estimate its impact on health-related quality of life (HRQoL) and mental health. MethodsData was drawn from a population-based cohort of children and adolescents, recruited between December 2021 and June 2022, in Geneva, Switzerland. We measured the impact of the pandemic via the Coronavirus impact scale, which assesses the multidimensional impact of the pandemic at the child and family level through parents report. A score higher than one standard deviation above the mean was deemed a severe impact. Parents additionally reported about their offspring HRQoL and mental health with validated scales. Determinants of having been severely impacted were assessed with logistic models, as were the associations between having experienced a severe impact and poor HRQoL or mental health. ResultsOut of 2101 participants aged 2-17, 12.7% had experienced a severe pandemic impact. Having a lasting health condition, a pandemic-related worsening of lifestyle habits or an unfavorable family environment were associated with having been severely impacted by the pandemic. Participants who had experienced a severe pandemic impact were more likely to present poor HRQoL (aOR=3.1; 95%CI: 2.3-4.4) and poor mental health (aOR=3.9; 95%CI: 2.5-6.2). ConclusionsThe COVID-19 pandemic may have persistent consequences on the wellbeing of children and adolescents, especially among those with health and family vulnerabilities.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22279150

RESUMEN

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectivesC_ST_ABSPost-COVID syndrome remain poorly studied in children and adolescents. In this study, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Study designWe used data from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), which included children (aged 6 months to 17 years) selected from random samples drawn from state registries or who had a household member participating in a COVID-19 seroprevalence study conducted by our group. Children were tested for anti-SARS-CoV-2 N antibodies. Parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID syndrome. ResultsFrom December 1st, 2021 to February 16th, 2022, 1034 children were included, among whom 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference ({Delta}aPrev) of 4.1% (95%CI: 1.1;7.3). After stratification by age group, the prevalence was higher among adolescents aged 12-17 years ({Delta}aPrev=8.3%, 95%CI: 3.5;13.5) than among younger children (0.0%, 95%CI: -5.2;5.2 among 6-11 years old and 4.2%; 95%CI: -4.4;13.3 among 0-5 years old). The most frequently declared persistent symptoms among seropositives were smell loss, trouble concentrating and abdominal pain. Older age, having a chronic condition and lower socioeconomic conditions were identified as risk factors. ConclusionA significant proportion of seropositive children, particularly adolescents, experienced persistent symptoms. While there is a need for further investigation, growing evidence of pediatric post-COVID syndrome urges early screening and primary care management.

4.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22278126

RESUMEN

BackgroundMore than two years into the COVID-19 pandemic, it is generally assumed that most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. We thus aimed to estimate anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. MethodsWe conducted a population-based serosurvey between April 29th and June 9th, 2022, recruiting children and adults of all ages from age-stratified random samples of the Geneva general population. Anti-SARS-CoV-2 antibody presence was assessed using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein. Antibodies neutralization capacity against different SARS-CoV-2 variants was evaluated using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. Seroprevalence of anti-SARS-CoV-2 antibodies and neutralization capacity were estimated using Bayesian modeling frameworks accounting for the demographics, vaccination, and infection statuses of the Geneva population. ResultsAmong the 2521 individuals included in the analysis (55.2% women; 21.4% aged <18 years and 14.2% aged [≥] 65 years), overall seroprevalence of antibodies was 93.8% (95% credible interval: 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies based on a representative subsample of 1160 participants ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged <12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. In general, higher levels of neutralization activity against pre-Omicron variants were associated with vaccination, particularly having received a booster dose. Higher levels of neutralization activity against Omicron subvariants were associated with booster vaccination alongside recent infection. ConclusionMore than nine in ten individuals in the Geneva population have developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, but less than half of the population has antibodies with neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection appears to confer the greatest neutralization capacity, including against Omicron.

5.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22274838

RESUMEN

BackgroundSARS-CoV-2 infection and its health consequences have disproportionally affected disadvantaged socio-economic groups globally. This study aimed to analyze the association between socio-economic conditions and having developed anti-SARS-CoV-2 antibodies in a population-based sample in the canton of Geneva, Switzerland. MethodsData was obtained from a population-based serosurvey of adults in Geneva and their household members, between November and December, 2020, towards the end of the second pandemic wave in the canton. Participants were tested for anti-SARS-CoV-2 antibodies. Socio-economic conditions representing different dimensions were self-reported. Mixed effects logistic regressions were conducted for each predictor to test its association with seropositive status as the main outcome. Results2,889 adults completed the study questionnaire and were included in the final analysis. Retired participants and those living in suburban areas had lower odds of a seropositive result when compared to employed participants (OR 0.42, 95% CI - 0.20 - 0.87) and those living in urban areas (OR 0.67, 95% CI - 0.46 - 0.97), respectively. People facing financial hardship for less than a year had higher odds of a seropositive result compared to those who had never faced them (OR 2.23, 95% CI - 1.01 - 4.95). Educational level, occupational position and household income were not associated with being seropositive, nor were ethnicity or country of birth. DiscussionWhile traditional measures of socio-economic position did not seem to be related to the risk of being infected in this sample, this study sheds lights on the importance of examining the broader social determinants of health when evaluating the differential impact of the pandemic within the population.

6.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22274436

RESUMEN

BackgroundThe rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics. MethodsConvalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants. FindingsPrior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants. InterpretationModerately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination. FundingEPFL COVID Fund; private foundation advised by CARIGEST SA; Private Foundation of the Geneva University Hospitals; General Directorate of Health of the canton of Geneva, the Swiss Federal Office of Public Health.

7.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21268224

RESUMEN

BackgroundVarious studies showed the negative impact of COVID-19-related lockdowns and school closures on the well-being of children and adolescents. However, the prevalence and consequences of occasional short-term school disruptions due to COVID-19-related quarantine or isolation remain unknown. This study evaluated their impact on the well-being and stress level of children and adolescents. MethodsIn June/July 2021, we conducted a survey selecting a representative sample of children and adolescents of a Swiss canton population. Parents of school-aged children reported information about them missing school because of COVID-19, from August 2020 to June 2021, as well as about their health-related quality of life (HRQoL) measured with the KINDL(R) scale and their stress level. ResultsAmong the 538 participants, 216/538 (40.1%) pupils missed school at least once for COVID-19-related causes, with a total of 272 absences. We observed no relationship between the frequency of COVID-19-related absences and the HRQoL or stress level, even when stratifying by the type of absence or socio-demographic factors. DiscussionOverall, these findings are reassuring in that quarantines and related school disruptions, which we know are a common and effective way of controlling SARS-CoV-2 transmission, did not seem to meaningfully impact children and adolescents wellbeing and stress. Finding the right balance between SARS-CoV-2 control and young populations well-being is challenging, and the current results provide additional information for decision makers.

8.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21268298

RESUMEN

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSIt is now established that a significant proportion of adults experience persistent symptoms after SARS-CoV-2 infection. However, evidence for children and adolescents is still inconclusive. In this population-based study, we examine the proportion of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection, as assessed by serological status, and compare this to a seronegative control group. MethodsWe conducted a serosurvey in June-July 2021, recruiting 660 children and adolescents from 391 households selected randomly from the Geneva population. We tested participants for anti-SARS-CoV-2 antibodies targeting the nucleocapsid (N) protein to determine previous infection. A parent filled a questionnaire including questions on COVID-19-related symptoms lasting at least 2 weeks. FindingsAmong children seropositive for anti-SARS-CoV-2 antibodies, the sex- and age-adjusted prevalence of symptoms lasting longer than two weeks was 18.3%, compared to 11.1% among seronegative children (prevalence difference ({Delta}aPrev)=7.2%, 95%CI:1.5-13.0). Main symptoms declared among seropositive children were fatigue (11.5%) and headache (11.1%). For 8.6% (aPrev, 95%CI: 4.7-12.5) of seropositives, these symptoms were declared to be highly limiting of daily activities. Adolescents aged 12-17 years had a higher adjusted prevalence of persistent symptoms (aPrev=29.1%, 95%CI:19.4-38.7) than younger children. Comparing seropositive and seronegative adolescents, the estimated prevalence of symptoms lasting over four weeks is 4.4% ({Delta}aPrev, 95%CI:-3.8-13.6). InterpretationA significant proportion of children aged 12 to 17 years had symptoms lasting over two weeks after SARS-CoV-2 infection, with an estimated prevalence of symptoms lasting over 4 weeks of 4.4% in this age group. This represents a large number of adolescents in absolute terms, and should raise concern in the context of unknown long-term evolution of symptoms. Younger children appear to experience long-lasting symptoms less frequently, as no difference was observed between the seropositive and seronegative sample. Further studies with larger samples sizes are needed. FundingSwiss Federal Office of Public Health, Geneva General Directorate of Health, HUG Private Foundation, SSPH+, Fondation des Grangettes.

9.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21265509

RESUMEN

We report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school, as part of a longitudinal, prospective, primary school-based surveillance study. It involved repeated testing of pupils and teachers and household members of participants who tested positive, with rapid antigen tests and/or RT-PCR (Day 0-2 and Day 5-7), serologies on dried capillary blood samples (Day 0-2 and Day 30), contact tracing interviews and SARS-CoV-2 whole genome sequencing. This SARS-CoV-2 outbreak caused by the Alpha variant involved 20 children aged 4 to 6 years from 4 classes, 2 teachers and a total of 4 household members. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 classes, 22.2% among teachers and 0% among non-teaching staff. Secondary attack rate among household members was 15.4%. Symptoms were reported by 63% of infected children, 100% of teachers and 50% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests. This study confirmed child-to-child and child-to-adult transmission of the infection. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.

10.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21264411

RESUMEN

BackgroundHealth systems around the world continue to navigate through operational challenges surfaced by the COVID-19 pandemic; these have implications for access to healthcare. In this study, we estimate the prevalence and reasons for forgoing healthcare during the pandemic in Geneva, Switzerland; a country with a universal and mandatory private health insurance coverage. MethodsParticipants from a randomly selected population-based sample of the adult population living in the Canton of Geneva completed an online socio-demographic and lifestyle questionnaire between November 2020 and January 2021. The prevalence and reasons for forgoing healthcare since the beginning of the COVID-19 pandemic were examined descriptively, and logistic regression models were used to assess determinants for forgoing healthcare. ResultsThe study included 5,397 participants, among which 8.0% reported having forgone healthcare since the beginning of the COVID-19 pandemic; participants with a disadvantaged financial situation (OR=2.04; 95% CI: 1.56-2.65), and those reporting an average (OR=2.55; 95% CI: 1.94-3.32) or poor health (OR=4.40; 95% CI: 2.40-7.68) were more likely to forgo healthcare. The most common reasons to forgo healthcare were appointment cancellations by healthcare providers (53.9%), fear of infection (35.3%), and personal organizational issues (11.1%). ConclusionOur paper highlights the effects of the COVID-19 pandemic on access to healthcare and identifies population sub-groups at-risk for forgoing healthcare. These results necessitate public health efforts to ensure equitable and accessible healthcare as the COVID-19 pandemic continues. HighlightsO_LI8% of the Geneva, Switzerland, adults renounced healthcare in the COVID-19 pandemic C_LIO_LIMain forgoing healthcare reasons are appointment cancellation and fear of infection C_LIO_LIUnderprivileged participants with poor health are more likely to forgo healthcare C_LI

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