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

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 widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show 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 previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave 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. 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.

Household transmission dynamics of seasonal human coronaviruses.

BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over two respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, HCoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. RESULTS: Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children (<19y) displayed ILI symptoms than infected adults (relative risk 3.0, 95% credible interval (CrI) 1.5, 6.9). The estimated weekly household transmission probability was 9% (95% CrI 6, 13) and weekly community acquisition probability was 7% (95% CrI 5, 10). We found no evidence for differences in community or household transmission probabilities by age or symptom status. Simulations suggest that our study was underpowered to detect such differences. CONCLUSION: Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs.

Assessing the impact of non-pharmaceutical interventions on SARS-CoV-2 transmission in Switzerland.

Following the rapid dissemination of COVID-19 cases in Switzerland, large-scale non-pharmaceutical interventions (NPIs) were implemented by the cantons and the federal government between 28 February and 20 March 2020. Estimates of the impact of these interventions on SARS-CoV-2 transmission are critical for decision making in this and future outbreaks. We here aim to assess the impact of these NPIs on disease transmission by estimating changes in the basic reproduction number (R0) at national and cantonal levels in relation to the timing of these NPIs. We estimated the time-varying R0 nationally and in eleven cantons by fitting a stochastic transmission model explicitly simulating within-hospital dynamics. We used individual-level data from more than 1000 hospitalised patients in Switzerland and public daily reports of hospitalisations and deaths. We estimated the national R0 to be 2.8 (95% confidence interval 2.1–3.8) at the beginning of the epidemic. Starting from around 7 March, we found a strong reduction in time-varying R0 with a 86% median decrease (95% quantile range [QR] 79–90%) to a value of 0.40 (95% QR 0.3–0.58) in the period of 29 March to 5 April. At the cantonal level, R0 decreased over the course of the epidemic between 53% and 92%. Reductions in time-varying R0 were synchronous with changes in mobility patterns as estimated through smartphone activity, which started before the official implementation of NPIs. We inferred that most of the reduction of transmission is attributable to behavioural changes as opposed to natural immunity, the latter accounting for only about 4% of the total reduction in effective transmission. As Switzerland considers relaxing some of the restrictions of social mixing, current estimates of time-varying R0 well below one are promising. However, as of 24 April 2020, at least 96% (95% QR 95.7–96.4%) of the Swiss population remains susceptible to SARS-CoV-2. These results warrant a cautious relaxation of social distance practices and close monitoring of changes in both the basic and effective reproduction numbers.

Seroprevalence of anti-SARS-CoV-2 antibodies and cross-variant neutralization capacity after the Omicron BA.2 wave in Geneva, Switzerland: A population-based study.

Background: More than two years into the COVID-19 pandemic, 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. Here, we estimated 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 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population. Findings: Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) 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. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants. Interpretation: While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron. Funding: General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

Comparison of COVID-19 Pandemic Waves in 10 Countries in Southern Africa, 2020-2021.

We used publicly available data to describe epidemiology, genomic surveillance, and public health and social measures from the first 3 COVID-19 pandemic waves in southern Africa during April 6, 2020-September 19, 2021. South Africa detected regional waves on average 7.2 weeks before other countries. Average testing volume 244 tests/million/day) increased across waves and was highest in upper-middle-income countries. Across the 3 waves, average reported regional incidence increased (17.4, 51.9, 123.3 cases/1 million population/day), as did positivity of diagnostic tests (8.8%, 12.2%, 14.5%); mortality (0.3, 1.5, 2.7 deaths/1 million populaiton/day); and case-fatality ratios (1.9%, 2.1%, 2.5%). Beta variant (B.1.351) drove the second wave and Delta (B.1.617.2) the third. Stringent implementation of safety measures declined across waves. As of September 19, 2021, completed vaccination coverage remained low (8.1% of total population). Our findings highlight opportunities for strengthening surveillance, health systems, and access to realistically available therapeutics, and scaling up risk-based vaccination.

Protocol to implement a syndromic surveillance survey of COVID-19 in Malawi.

Introduction: Malawi experienced two waves of COVID-19 between April 2020 and February 2021. A High negative impact of COVID-19 was experienced in the second wave, with increased hospital admissions that overwhelmed the healthcare system. This paper describes a protocol to implement a telephone-based syndromic surveillance system to assist public health leaders in the guidance, implementation, and evaluation of programs and policies for COVID-19 prevention and control in Malawi. Study design: This is a serial cross-sectional telephonic-based national survey focusing on the general population and People living with HIV and AIDS. Methods: We will conduct a serial cross-sectional telephone survey to assess self-reported recent and current experience of influenza-like illness (ILI)/COVID-19-like-illness (CLI), household deaths, access to routine health services, and knowledge related to COVID-19. Structured questionnaires will be administered to two populations: 1) the general population and 2) people living with HIV (PLHIV) on antiretroviral therapy (ART) at EGPAF-supported health facilities. Electronic data collection forms using secure tablets will be used based on randomly selected mobile numbers from electronic medical records (EMR) for PLHIV. We will use random digit dialing (RDD) for the general population to generate phone numbers to dial respondents. The technique uses computer-generated random numbers, using the 10-digit basic structure of mobile phone numbers for the two existing mobile phone companies in Malawi. Interviews will be conducted only with respondents that will verbally consent. A near real-time online dashboard will be developed to help visualize the data and share results with key policymakers. Conclusion: The designed syndromic surveillance system is low-cost and feasible to implement under COVID-19 restrictions, with no physical contact with respondents and limited movement of the study teams and communities. The system will allow estimation proportions of those reporting ILI/CLI among the general population and PLHIV on ART and monitor trends over time to detect locations with possible COVID-19 transmission. Reported household deaths in Malawi, access to health services, and COVID-19 knowledge will be monitored to assess the burden and impact on communities in Malawi.

Epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak (Alpha variant) in a primary school: A prospective longitudinal study.

OBJECTIVES: To report a prospective epidemiological, virological and serological investigation of a SARS-CoV-2 outbreak in a primary school. METHODS: As part of a longitudinal, prospective, school-based surveillance study, this investigation involved repeated testing of 73 pupils, 9 teachers, 13 non-teaching staff and 26 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. RESULTS: We identified 20 children (aged 4 to 6 years from 4 school classes), 2 teachers and a total of 4 household members who were infected by the Alpha variant during this outbreak. Infection attack rates were between 11.8 and 62.0% among pupils from the 4 school 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. CONCLUSIONS: This study confirmed child-to-child and child-to-adult SARS-CoV-2 transmission and introduction into households. Effective measures to limit transmission in schools have the potential to reduce the overall community circulation.

Applying mixture model methods to SARS-CoV-2 serosurvey data from Geneva.

Serosurveys are an important tool to estimate the true extent of the current SARS-CoV-2 pandemic. So far, most serosurvey data have been analyzed with cutoff-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%-9.9%)), 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 hospitalized 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.

SARS-CoV-2 Antibody Prevalence and Population-Based Death Rates, Greater Omdurman, Sudan.

In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.

In-person schooling and associated COVID-19 risk in the United States over spring semester 2021.

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 this pandemic. Previous work in the United States during winter 2020-2021 showed that in-person schooling carried some risk for household members and that mitigation measures reduced this risk. Schooling and the COVID-19 landscape changed radically over spring semester 2021. 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 increases in in-person schooling and reductions in mitigations over time. In-person schooling is associated with increased reporting of COVID-19 outcomes even among vaccinated individuals (although the absolute risk among the vaccinated is greatly reduced). Vaccinated teachers working outside the home were less likely to report COVID-19-related outcomes than unvaccinated teachers working exclusively from home. Adequate mitigation measures appear to eliminate the excess risk associated with in-person schooling.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Global landscape of SARS-CoV-2 genomic surveillance and data sharing.

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study.

Aims: To assess SARS-CoV-2 seroprevalence over the first epidemic wave in the canton of Geneva, Switzerland, as well as risk factors for infection and symptoms associated with IgG seropositivity. Methods: Between April and June 2020, former participants of a representative survey of the 20-74-year-old population of canton Geneva were invited to participate in the study, along with household members aged over 5 years. Blood samples were tested for anti-SARS-CoV-2 immunoglobulin G. Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. Results: We included 8344 participants, with an overall adjusted seroprevalence of 7.8% (95% credible interval 6.8-8.9). Seroprevalence was highest among 18-49 year-olds (9.5%), and lowest in 5-9-year-old children (4.3%) and individuals >65 years (4.7-5.4%). Odds of seropositivity were significantly reduced for female retirees and unemployed men compared to employed individuals, and smokers compared to non-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. The symptom most strongly associated with seropositivity was anosmia/dysgeusia. Conclusions: Anti-SARS-CoV-2 population seroprevalence remained low after the first wave in Geneva. Socioeconomic factors were not associated with seropositivity in this sample. The elderly, young children and smokers were less frequently seropositive, although it is not clear how biology and behaviours shape these differences.

Risk of Reinfection After Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Population-based Propensity-score Matched Cohort Study.

BACKGROUND: Serological assays detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being widely deployed in studies and clinical practice. However, the duration and effectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals as compared to seronegative controls, we conducted a retrospective longitudinal matched study. METHODS: A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland, between April and June 2020, immediately after the first pandemic wave. Seropositive participants were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index (BMI), smoking status, and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confirmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021). RESULTS: Among 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 whom 5 (1.0%) were classified as reinfections. In contrast, the infection rate was higher in seronegative individuals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95% confidence interval [CI]: 86%- 98%, P < .001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives. CONCLUSIONS: Seroconversion after SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.

Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis.

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection-mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6-4.7-fold), 1.8-fold (1.4-2.4-fold), and 3.2-fold (2.4-4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2-1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5-9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7-4.4-fold) for messenger RNA platform, and 2.5-fold (1.7-2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.

Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: A rapidly increasing number of serological surveys for antibodies to SARS-CoV-2 have been reported worldwide. We aimed to synthesise, combine, and assess this large corpus of data. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and five preprint servers for articles published in English between Dec 1, 2019, and Dec 22, 2020. Studies evaluating SARS-CoV-2 seroprevalence in humans after the first identified case in the area were included. Studies that only reported serological responses among patients with COVID-19, those using known infection status samples, or any animal experiments were all excluded. All data used for analysis were extracted from included papers. Study quality was assessed using a standardised scale. We estimated age-specific, sex-specific, and race-specific seroprevalence by WHO regions and subpopulations with different levels of exposures, and the ratio of serology-identified infections to virologically confirmed cases. This study is registered with PROSPERO, CRD42020198253. FINDINGS: 16 506 studies were identified in the initial search, 2523 were assessed for eligibility after removal of duplicates and inappropriate titles and abstracts, and 404 serological studies (representing tests in 5 168 360 individuals) were included in the meta-analysis. In the 82 studies of higher quality, close contacts (18·0%, 95% CI 15·7-20·3) and high-risk health-care workers (17·1%, 9·9-24·4) had higher seroprevalence than did low-risk health-care workers (4·2%, 1·5-6·9) and the general population (8·0%, 6·8-9·2). The heterogeneity between included studies was high, with an overall I2 of 99·9% (p<0·0001). Seroprevalence varied greatly across WHO regions, with the lowest seroprevalence of general populations in the Western Pacific region (1·7%, 95% CI 0·0-5·0). The pooled infection-to-case ratio was similar between the region of the Americas (6·9, 95% CI 2·7-17·3) and the European region (8·4, 6·5-10·7), but higher in India (56·5, 28·5-112·0), the only country in the South-East Asia region with data. INTERPRETATION: Antibody-mediated herd immunity is far from being reached in most settings. Estimates of the ratio of serologically detected infections per virologically confirmed cases across WHO regions can help provide insights into the true proportion of the population infected from routine confirmation data. FUNDING: National Science Fund for Distinguished Young Scholars, Key Emergency Project of Shanghai Science and Technology Committee, Program of Shanghai Academic/Technology Research Leader, National Science and Technology Major project of China, the US National Institutes of Health. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.