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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.
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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.
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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.
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Because of the importance of schools to childhood development, the relationship between in-person schooling and COVID-19 risk has been one of the most important questions of the COVID-19 pandemic. Previous work using data from the United States in winter 2020-21 showed that in-person schooling carried some risk for household members, and that mitigation measures reduced this risk. However, in-person schooling behavior and the COVID-19 landscape changed radically over the 2021 spring semester. Here we use data from a massive online survey to characterize changes in in-person schooling behavior and associated risks over that period. We find a significant increase in the frequency of in-person schooling and a reduction in mitigation, and that in-person schooling is associated with increased reporting of COVID-19 outcomes, even among vaccinated individuals (though the absolute risk among the vaccinated is greatly reduced). Moreover, vaccinated teachers working outside the home were less likely to report COVID-19-related outcomes than unvaccinated teachers reporting no work outside the home. Adequate mitigation measures appear to eliminate the excess risk associated with in person schooling.
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The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.
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BackgroundEven after adjusting for the expected lower severity due to the younger age of the population, relatively low SARS-CoV-2 incidence and mortality rates have been reported throughout Africa. For investigating whether this is truly the case, we conducted a survey to estimate the COVID-19 related mortality and cumulative incidence of SARS-CoV-2 infections in Omdurman the most populated city of the tripartite metropolis Khartoum in Sudan. MethodsA retrospective, cross-sectional, mortality and seroprevalence survey was conducted in Omdurman, Sudan, from March 1, until April 10 2021. A two-stage cluster sampling method was used to investigate the death rate for the pre-pandemic (January 1, 2019-February 29, 2020) and pandemic (March 1, 2020 - day of the survey) period using questionnaires. The seroprevalence survey was performed in a subset of households and all consenting members were tested with a rapid serological test (SD-Biosensor) and a subgroup additionally with ELISA (EUROIMMUN). Fishers exact test was used to assess differences between the pre-and pandemic periods and a random effect and Bayesian latent class model to adjust for test performance. FindingsData from 27315 people (3716 households) for the entire recall period showed a 67% (95% CI 32-110) increase in death rate between the pre-pandemic (0.12 deaths/10000 people/day [95% CI 0.10-0.14]) and pandemic (0.20 [0.16-0.23]) periods. Notably, a 74% (30-133) increase in death was observed among people aged [≥]50 years. The adjusted seroprevalence of SARS-CoV-2 was 54.6% (95% CI 51.4-57.8). The seroprevalence was significantly associated with age, increasing up to 80.7% (71.7-89.7) for the oldest age group ([≥]50 years). InterpretationOur results showed a significant elevated mortality for the pandemic period with a considerable excess mortality in Omdurman, Sudan. The overall high seroprevalence indicated a different age pattern compared to other countries, with a significant increase by age. FundingMedecins Sans Frontieres
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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.
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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.
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BackgroundCamps of forcibly displaced populations are considered to be at risk of large COVID-19 outbreaks. Low screening rates and limited surveillance led us to conduct a study in Dagahaley camp, located in the Dadaab refugee complex in Kenya to estimate SARS-COV-2 seroprevalence and, mortality and to identify changes in access to care during the pandemic. MethodsTo estimate seroprevalence, we conducted a cross-sectional survey among a sample of individuals (n=587) seeking care at the two main health centres and among all household members (n=619) of community health workers and traditional birth attendants working in the camp. We used a rapid immunologic assay (BIOSYNEX(R) COVID-19 BSS [IgG/IgM]) and adjusted for test performance and mismatch between the sampled population and that of the general camp population. To estimate mortality, we exhaustively interviewed all households (n=12860) in the camp about deaths occurring from January 2019 through March 2021. ResultsWe included 1206 participants in the seroprevalence study. In total, 8% (95% CI: 6.6%-9.7%) had a positive serologic test. After adjusting for test performance and standardizing on age, we estimated a seroprevalence of 5.8% (95% CI: 1.6%-8.4%). The mortality rate for 10,000 persons per day was 0.05 (95% CI 0.05-0.06) prior to the pandemic and 0.07 (95% CI 0.06-0.08) during the pandemic, representing a significant 42% increase (p<0.001). MSF health centre consultations and hospital admissions decreased by 38% and 37% respectively. ConclusionWe estimated that the number of infected people was 67 times higher than the number of reported cases. Participants aged 50 years or more where among the most affected. The mortality survey shows an increase in the mortality rate during the pandemic compared to before the pandemic. A decline in attendance at health facilities was observed and sustained despite the easing of restrictions. Summary BoxO_ST_ABSWhat is already known?C_ST_ABSO_LIAt the early stage of the COVID-19 pandemic, models predicted the risk of a large-scale COVID-19 outbreaks in camps of forcibly displaced populations that would have created excess mortality caused directly by the disease and indirectly by reduced access to care and/or congestion in health facilities. C_LIO_LITo date, this prediction has not materialized in most camps, the lower than expected number of cases and deaths could be attributed to a population characteristics and early implementation of confinement; alternatively, it could be an underestimate caused by limited screening and testing capacity and lack of morbidity and mortality surveillance. C_LIO_LIThe actual impact of COVID-19 on these populations therefore remains an open question. C_LI What are the new findings?O_LIIn Dagahaley camps in Kenya, we estimated that the number of infected people was 67 times higher than the number of reported cases. C_LIO_LIParticipants aged 50 years and over, who are most at risk of severe illness, were among the most affected. C_LIO_LIWe observed an increase in mortality rates during the pandemic, and a decrease in the use of health facilities, which continued despite the easing of restrictions, but access for severe cases was less impacted. C_LI What do the new findings imply?O_LITo our knowledge, this is the first combined survey of COVID-19 seroprevalence and retrospective mortality in a forcibly displaced population living in a camp. C_LIO_LIDespite mitigation measures, the virus has circulated, which should prompt rapid vaccination as most of the population remains susceptible; the collateral effects of the pandemic on access to care must be addressed and public confidence restored in order to limit the risk of excess mortality. C_LIO_LIThe varying situations of forcibly displaced populations living in camps around the world support the need for further research at other sites. C_LI
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In a representative serosurvey conducted March-June 2021, 64.1% (95%CrI 60.0- 68.1%) of Sitakunda subdistrict (Bangladesh) had anti-SARS-CoV-2 IgG antibodies after adjusting for age, sex, household clustering and test performance. Before the surge of Delta, most of the population had been infected despite low incidence of virologically-confirmed COVID-19.
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Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analysed with cut-off based methods, which dichotomize individual measurements into sero-positives or negatives based on a predefined cutoff. However, mixture model methods can gain additional information from the same serosurvey data. Such methods refrain from dichotomizing individual values and instead use the full distribution of the serological measurements from pre-pandemic and COVID-19 controls to estimate the cumulative incidence. This study presents an application of mixture model methods to SARS-CoV-2 serosurvey data from the SEROCoV-POP study from April and May 2020 in Geneva (2766 individuals). Besides estimating the total cumulative incidence in these data (8.1% (95% CI: 6.8% - 9.8%)), we applied extended mixture model methods to estimate an indirect indicator of disease severity, which is the fraction of cases with a distribution of antibody levels similar to hospitalised COVID-19 patients. This fraction is 51.2% (95% CI: 15.2% - 79.5%) across the full serosurvey, but differs between three age classes: 21.4% (95% CI: 0% - 59.6%) for individuals between 5 and 40 years old, 60.2% (95% CI: 21.5% - 100%) for individuals between 41 and 65 years old and 100% (95% CI: 20.1% - 100%) for individuals between 66 and 90 years old. Additionally, we find a mismatch between the inferred negative distribution of the serosurvey and the validation data of pre-pandemic controls. Overall, this study illustrates that mixture model methods can provide additional insights from serosurvey data.
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BackgroundSince the emergence of the COVID-19 pandemic, substantial concern has surrounded its impact among the Rohingya refugees living in the Kutupalong-Balukhali refugee camps in Bangladesh. Early modeling work projected a massive outbreak was likely after an introduction of the SARS-CoV-2 virus into the camps. Despite this, only 317 laboratory-confirmed cases and 10 deaths were reported through October 2020. While these official numbers portray a situation where the virus has been largely controlled, other sources contradict this, suggesting the low reported numbers to be a result of limited care seeking and testing, highlighting a population not willing to seek care or be tested. SARS-CoV-2 seroprevalence estimates from similar a timeframe in India (57%) and Bangladesh (74%) further sow doubt that transmission had been controlled. Here we explore multiple data sources to understand the plausibility of a much larger SARS-CoV-2 outbreak among the Rohingya refugees. MethodsWe used a mixed approach to analyze SARS-CoV-2 transmission using multiple available datasets. Using data from reported testing, cases, and deaths from the World Health Organization (WHO) and from WHOs Emergency Warning, Alert, and Response System, we characterized the probabilities of care seeking, testing, and being positive if tested. Unofficial death data, including reported pre-death symptoms, come from a community-based mortality survey conducted by the International Organization for Migration (IOM),) in addition to community health worker reported deaths. We developed a probabilistic inference framework, drawing on these data sources, to explore three scenarios of what might have happened among the Rohingya refugees. ResultsAmong the 144 survey-identified deaths, 48 were consistent with suspected COVID-19. These deaths were consistent with viral exposures during Ramadan, a period of increased social contacts, and coincided with a spike in reported cases and testing positivity in June 2020. The age profile of suspected COVID-19 deaths mirrored that expected. Through the probability framework, we find that under each scenario, a substantial outbreak likely occurred, though the cumulative size and timing vary considerably. In conjunction with the reported and suspected deaths, the data suggest a large outbreak could have occurred early during spring 2020. Furthermore, while many mild and asymptomatic infections likely occurred, death data analyzed suggest there may have been significant unreported mortality. ConclusionsWith the high population density, inability to home isolate adequately, and limited personal protective equipment, infection prevention and control in the Rohingya population is extremely challenging. Despite the low reported numbers of cases and deaths, our results suggest an early large-scale outbreak is consistent with multiple sources of data, particularly when accounting for limited care seeking behavior and low infection severity among this young population. While the currently available data do not allow us to estimate the precise incidence, these results indicate substantial unrecognized SARS-CoV-2 transmission may have occurred in these camps. However, until serological testing provides more conclusive evidence, we are only able to speculate about the extent of transmission among the Rohingya.
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BackgroundImmunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. MethodsWe systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. FindingsWe identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). InterpretationOur findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. FundingChinese National Science Fund for Distinguished Young Scholars Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. Added value of this studyIn this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Implications of all the available evidenceOur findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.
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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.
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BackgroundRelatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys. MethodsWe conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance. ResultsWe recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections. ConclusionsSARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.
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In-person schooling has proved contentious and difficult to study throughout the SARS-CoV-2 pandemic. Data from a massive online survey in the United States indicates an increased risk of COVID-19-related outcomes among respondents living with a child attending school in-person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extra-curricular activities. With seven or more mitigation measures, the association between in-person schooling and COVID-19-related outcomes all but disappears. Teachers working outside the home were more likely to report COVID-19-related outcomes, but this association is similar to other occupations (e.g., healthcare, office work). In-person schooling is associated with household COVID-19 risk, but this risk can likely be controlled with properly implemented school-based mitigation measures. One sentence summaryLiving with children attending in-person school is linked to a higher risk of COVID-19 outcomes, which school-based interventions can mitigate.
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BackgroundKnowing the transmissibility of asymptomatic infections and risk of infection from household- and community-exposures is critical to SARS-CoV-2 control. Limited previous evidence is based primarily on virologic testing, which disproportionately misses mild and asymptomatic infections. Serologic measures are more likely to capture all previously infected individuals. ObjectiveEstimate the risk of SARS-CoV-2 infection from household and community exposures, and identify key risk factors for transmission and infection. DesignCross-sectional household serosurvey and transmission model. SettingGeneva, Switzerland Participants4,524 household members [≥]5 years from 2,267 households enrolled April-June 2020. MeasurementsPast SARS-CoV-2 infection confirmed through IgG ELISA. Chain-binomial models based on the number of infections within households used to estimate the cumulative extra-household infection risk and infection risk from exposure to an infected household member by demographics and infectors symptoms. ResultsThe chance of being infected by a SARS-CoV-2 infected household member was 17.3% (95%CrI,13.7-21.7%) compared to a cumulative extra-household infection risk of 5.1% (95%CrI,4.5-5.8%). Infection risk from an infected household member increased with age, with 5-9 year olds having 0.4 times (95%CrI, 0.07-1.4) the odds of infection, and [≥]65 years olds having 2.7 (95%CrI,0.88-7.4) times the odds of infection of 20-49 year olds. Working-age adults had the highest extra-household infection risk. Seropositive asymptomatic household members had 69.6% lower odds (95%CrI,33.7-88.1%) of infecting another household member compared to those reporting symptoms, accounting for 14.7% (95%CrI,6.3-23.2%) of all household infections. LimitationsSelf-reported symptoms, small number of seropositive kids and imperfect serologic tests. ConclusionThe risk of infection from exposure to a single infected household member was more than three-times that of extra-household exposures over the first pandemic wave. Young children had a lower risk of infection from household members. Asymptomatic infections are far less likely to transmit than symptomatic ones but do cause infections. Funding SourceSwiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privee des Hopitaux Universitaires de Geneve, and Center for Emerging Viral Diseases.
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BackgroundA rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. PurposeTo evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sourcesWe searched PubMed, Embase, Web of Science, and 4 pre-print servers for English-language papers published from December 1, 2019 to September 25, 2020. Study selectionSerological studies evaluating SARS-CoV-2 seroprevalence in humans. Data extractionTwo investigators independently extracted data from studies. Data SynthesisMost of 230 serological studies, representing tests in >1,400,000 individuals, identified were of low quality based on a standardized study quality scale. In the 51 studies of higher quality, high-risk healthcare workers had higher seroprevalence of 17.1% (95% CI: 9.9-24.4%), compared to low-risk healthcare workers and general population of 5.4% (0.7-10.1%) and 5.3% (4.2-6.4%). Seroprevalence varied hugely across WHO regions, with lowest seroprevalence of general population in Western Pacific region (1.7%, 0.0-5.0%). Generally, the young (<20 years) and the old ([≥]65 years) were less likely to be seropositive compared to middle-aged (20-64 years) populations. Seroprevalence correlated with clinical COVID-19 reports, with pooled average of 7.7 (range: 2.0 to 23.1) serologically-detected-infections per confirmed COVID-19 case. LimitationsSome heterogeneity cannot be well explained quantitatively. ConclusionsThe overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given the relatively narrow range of estimates of the ratio of serologically-detected infections to confirmed cases across different locales, reported case counts may help provide insights into the true proportion of the population infected. Primary Funding sourceNational Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).
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The number of COVID-19 deaths is often used as a key indicator of SARS-CoV-2 epidemic size. However, heterogeneous burdens in nursing homes and variable reporting of deaths in elderly individuals can hamper comparisons of deaths and the number of infections associated with them across countries. Using age-specific death data from 45 countries, we find that relative differences in the number of deaths by age amongst individuals aged <65 years old are highly consistent across locations. Combining these data with data from 15 seroprevalence surveys we demonstrate how age-specific infection fatality ratios (IFRs) can be used to reconstruct infected population proportions. We find notable heterogeneity in overall IFR estimates as suggested by individual serological studies and observe that for most European countries the reported number of deaths amongst [≥]65s are significantly greater than expected, consistent with high infection attack rates experienced by nursing home populations in Europe. Age-specific COVID-19 death data in younger individuals can provide a robust indicator of population immunity.
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BACKGROUNDCharacterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODSWe measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTSBetween 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONSAmong symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.
