Immune escape of Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1 after vaccination, infection and hybrid immunity (preprint)

Since their emergence in late 2021, SARS-CoV-2 Omicron replaced earlier variants of concern and marked a new phase in the SARS-CoV-2 pandemic. Until the end of 2023, Omicron lineages continue to circulate and continue to evolve, with new lineages causing infection waves throughout 2022 and 2023. In the population, this leads to a complex immunological exposure background, characterized by immunity derived through vaccination, in the 5th year of the pandemic in the majority of individuals followed by at least one or even multiple infections or only natural infection in individuals that did not receive a vaccine. In this study, we use eight authentic SARS-CoV-2 isolates (ancestral lineage B.1 and the seven Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1) in a live virus neutralization assay to study immune escape in 97 human sera or plasma of different immunological backgrounds (vaccination, hybrid immunity due to one or two natural infections and natural infection without vaccination in children and adults). We showed a gradually increasing immune escape after vaccination and hybrid immunity in from B.1 to BA.1/BA.2 to BA.5.1 to BQ.1 to XBB.1.5 to EG.5.1, but remarkably, no more enhanced immune escape of JN.1.1 compared to EG.5.1, with the latter two showing almost identical neutralization titers in individuals with hybrid immunity due to one or more infections. In vaccinated but never infected individuals, neutralization was markedly reduced or completely lost for XBB.1.5., EG.5.1 and JN.1.1, while in those with hybrid immunity, titers were reduced but almost all sera still showed some degree of neutralization. After a single infection without vaccination, reduced or complete loss of neutralization occurred for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 compared to BA.1/BA.2. Furthermore, we observed that, although absolute titers differed between groups, the pattern of immune escape between the variants remains comparable across groups, with strongest loss of neutralization for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 was observed across the different immunological backgrounds. Our results show gradually increasing antibody escape of evolving Omicron lineages over the last two years of Omicron circulation until variant EG.5.1, but not anymore for the currently dominant lineages JN.1.1, suggesting other mechanisms than immune escape to be behind the rapid global emergence of JN.1.

COVID-19 Fears and Preventive Behaviors among Prison Staff

This study focused on COVID-19 preventive behaviors and fears among prison staff members after the first wave of the pandemic. Cross-sectional data from 171 participants were collected in Switzerland. The level of fears (58.5%) and protective behaviors (100%) were high. Correctional officers adhered less to preventive measures than other staff members (p = .001). Fears were related to a reduction of social contacts (p = .006) and worries about physical health was related to preventive behaviors in general (p = .006). There is a need to raise prison staff awareness regarding their vulnerability to the SARS-CoV-2 in order to improve the effectiveness of health campaigns in prison settings. Special attention should be given to correctional officers.

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection (preprint)

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 1'083 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 show 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 levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. Taken together these results indicate that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals with a history of previous SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will come next, these results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

Impact of the COVID-19 pandemic on children and adolescents: determinants and association with quality of life and mental health - A cross-sectional study (preprint)

Background The 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. Methods Data 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 parent's 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. Results Out 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). Conclusions The COVID-19 pandemic may have persistent consequences on the wellbeing of children and adolescents, especially among those with health and family vulnerabilities.

Post-COVID syndrome prevalence and risk factors in children and adolescents: A population-based serological study (preprint)

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.

Seroprevalence of anti-SARS-CoV-2 antibodies and cross-variant neutralization capacity after the Omicron BA.2 wave in Geneva, Switzerland (preprint)

ABSTRACT Background More 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. Methods We conducted a population-based serosurvey between April 29 th and June 9 th , 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. Results Among 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. Conclusion More 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.

Socio-economic determinants of SARS-CoV-2 infection: results from a population-based serosurvey in Geneva, Switzerland (preprint)

Background SARS-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. Methods Data 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. Results 2,889 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. Discussion While 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.

Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity (preprint)

Background: The 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. Methods: Convalescent 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. Findings: Prior 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. Interpretation: Moderately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination.

COVID-19-related school disruptions and well-being of children and adolescents in Geneva (preprint)

Background Various 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. Methods In 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. Results Among 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. Discussion Overall, 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 adolescent's 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.

Persistent symptoms among children and adolescents with and without anti-SARS-CoV-2 antibodies: a population-based serological study in Geneva, Switzerland (preprint)

Background: It 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. Methods: We 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. Findings: Among 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). Interpretation: A 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.

Epidemiological, virological and serological investigation into a SARS-CoV-2 outbreak (Alpha variant) in a primary school in Geneva, Switzerland: a prospective longitudinal study (preprint)

Background Twenty-one months into the pandemic, the extent to which young children get infected and transmit SARS-CoV-2 in school settings remains controversial, in particular with variants of concern. We report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school in Geneva, Switzerland, in April-May 2021. Methods This outbreak investigation is part of a longitudinal, prospective, primary school-based surveillance study (SEROCoV-Schools). It involved repeated testing of pupils and teachers and household members of participants who tested positive. Rapid antigen tests and/or real-time reverse transcription polymerase chain reaction were performed at Day 0-2 and Day 5-7; serologies on dried capillary blood samples were performed at Day 0-2 and Day 30. Contact tracing interviews and SARS-CoV-2 whole genome sequencing were carried out for positive cases. Results This SARS-CoV-2 outbreak caused by the Alpha variant involved 20 children aged 4 to 6 years from 4 classes, 2 teachers and 3 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 10.7%. Symptoms were reported by 63% of infected children, 100% of teachers and 66.7% of household members. All analysed sequences but one showed 100% identity. Serological tests detected 8 seroconversions unidentified by SARS-CoV-2 virological tests. Conclusions This study confirmed child-to-child and child-to-adult transmission of the infection. SARS-CoV-2 can spread rapidly between children and adults in school settings, and is thereby introduced into households. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.

Seroprevalence of anti-SARS-CoV-2 antibodies six months into the vaccination campaign in Geneva, Switzerland (preprint)

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape in the population and guide public health measures. We aimed to estimate the seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and six months into the vaccination campaign. MethodsWe conducted a population-based cross-sectional serosurvey between June 1 and July 7, 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins (Roche Elecsys immunoassays). We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies). ResultsWe included 3355 individuals, of which 1814 (54.1%) were women, 697 (20.8%) were aged <18 years and 449 (13.4%) were aged [≥]65 years, 2161 (64.4%) tested positive for anti-S antibodies, and 906 (27.0%) tested positive for anti-N antibodies. The total seroprevalence of anti-SARS-CoV-2 antibodies was 66.1% (95% credible interval, 64.1-68.0). We estimated that 29.9% (28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies only via vaccination. Seroprevalence estimates were similar across sexes, but differed markedly across age groups, being lowest among children aged 0-5 years (20.8% [15.5-26.7]) and highest among older adults aged [≥]75 years (93.1% [89.6-96.0]). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with a higher educational level. ConclusionsMost adults have developed anti-SARS-CoV-2 antibodies, while most teenagers and children remain vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and socioeconomically disadvantaged groups, and to minimize spread among children.

Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study. (preprint)

ObjectivesThis cohort study including essential workers, assessed the{square}risk and incidence of SARS-CoV-2{square}infection during the second surge of COVID-19 according to baseline serostatus and occupational sector. MethodsEssential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralized registry compiling SARS-CoV-2 infections. Primary outcome was the number of virologically-confirmed infections from serological assessment (between May and September 2020) to January 25, 2021, according to baseline antibody status and stratified by three pre-defined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). Secondary outcomes included the incidence of infection. Results10457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645, and 3755 workers were classified under "Other essential occupations"). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during follow-up with no significant between-occupational group difference. ConclusionsA ten-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least six months after infection. Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSRisk of SARS-CoV-2 reinfection is low in the general population and among healthcare workers. What are the new findings?A ten-fold reduction of risk of being virologically tested positive reinfection is observed among anti-SARS-CoV-2 seropositive essential workers of different activity sectors, regardless of their occupation-related risk of exposure. How might this impact on policy or clinical practice in the foreseeable future?Vaccination could be delayed in individuals with previous history of SARS-CoV-2 infection with serologic confirmation, regardless of their occupational exposure. These observations need to be confirmed for new SARS-CoV-2 variants.

COVID-19 Vaccination acceptance in the canton of Geneva: A Cross-Sectional Population-Based Study (preprint)

Objective This study aimed to assess acceptance of COVID-19 vaccination as well as its sociodemographic and clinical determinants in a general population sample three months after the launch of the vaccination program in Switzerland. Methods In March 2021, an online questionnaire on vaccination acceptance was proposed to adults included in a longitudinal cohort study of previous population-based serosurveys carried out in the canton of Geneva. Questions were asked about COVID-19 vaccination acceptance, reasons of acceptance or refusal, and attitudes about vaccination in general. Data on demographic (age, sex, education, income, professional status, living conditions) and health-related characteristics (having a chronic disease, COVID-19 diagnosis, smoking status) were assessed at inclusion in the cohort (December 2020). Results Overall, 4’067 participants (completion rate of 77.4%) responded to the survey between March 17 and April 1, 2021. The mean age of respondents was 53.3 years and 56.0% were women. Most had completed tertiary education (64.7%) and over 60% were currently professionally active. At the time of the survey, 17.2% of respondents had already been vaccinated with at least one dose or had made an appointment to get vaccinated, and an additional 58.5% intended or rather intended to get vaccinated. The overall acceptance of COVID-19 vaccination was 75.7%, with a higher acceptance among men compared to women, older adults compared to younger adults, high-income individuals compared to those with a low income, participants living in urban and semi-urban areas compared to rural, and retirees and students compared to employed individuals. Acceptance was lower among individuals having completed apprenticeships and secondary education compared to those with tertiary education. The most common reasons reported by participants intending to get vaccinated were the desire to ‘get back to normal’, to protect themselves, their community and/or society, and their relatives or friends against the risk of infection by SARS-CoV-2, as well as the desire to travel. Less than half (45.6%) of participants having children were willing or rather willing to have their children vaccinated against COVID-19 if it were recommended by public health authorities. Conclusion Although our study found a 75.7% acceptance of COVID-19 vaccination, there were noticeable socio-demographic disparities in vaccination acceptance. These data will be useful for public health measures targeting hesitant populations when developing health communication strategies. These results will be updated over time with a new release of the survey in autumn 2021.

Persistence and detection of anti-SARS-CoV-2 antibodies: immunoassay heterogeneity and implications for serosurveillance (preprint)

Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. The reliability of serologic studies for quantifying the proportion of the population that have been infected depends on the extent of antibody decay as well as on assay performance in detecting both recent and older infections. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. In a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals tested with three widely-used immunoassays, antibodies persisted for at least 8 months after infection, although detection depended on immunoassay choice, with one of them missing up to 40% of past infections. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. As the immune landscape becomes more complex with naturally-infected and vaccinated individuals, assay choice and appropriate assay-performance-adjustment will become even more important for the interpretation of serologic studies.

Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study (preprint)

ImportanceSerological assays detecting specific IgG antibodies generated against the Spike protein following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are being widely deployed in research studies and clinical practice. However, the duration and the effectiveness of the protection conferred by the immune response against future infection remains to be assessed in a large population. ObjectiveTo estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals from a population-based sample as compared to seronegative controls. DesignRetrospective longitudinal propensity-score matched cohort study. SettingA seroprevalence survey including a population-based representative sample of the population from the canton of Geneva (Switzerland) was conducted between April and June 2020, immediately after the first pandemic wave. Each individual included in the seroprevalence survey was linked to a state centralized registry compiling virologically confirmed SARS-CoV-2 infections since the beginning of the pandemic. ParticipantsParticipants aged twelve years old and over, who developed anti-spike IgG antibodies were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index, smoking status and education level. ExposureSARS-CoV-2 seropositivity. Main outcomes and measuresOur primary outcome was virologically confirmed SARS-CoV-2 infections which occurred from serological status assessment in April-June 2020 to the end of the second pandemic wave (January 2021). Additionally, incidence of infections, rate of testing and proportion of positive tests were analysed. ResultsAmong 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (Standard Deviation, SD: 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of which 5 (1.0%) were considered as reinfections. By contrast, infection rate was significantly higher in seronegative individuals (15.5%, 154/996) during a similar mean follow-up of 34.7 (SD 3.2) weeks, corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositive subjects. Conclusions and relevanceSeroconversion after SARS-CoV-2 infection confers protection to successive viral contamination lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation. Key points QuestionDo SARS-CoV-2 antibodies confer protection against future infection? FindingsIn this retrospective matched cohort study nested in a representative sample of the general population of Geneva, Switzerland, we observed a 94% reduction in the hazard of being infected among participants with antibodies against SARS-CoV-2, when compared to seronegative controls, >8 months after initial serology assessment. MeaningSeroconversion to SARS-CoV-2 is associated with a large and sustained protection against reinfection.