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.

Prevalence of Post-Coronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status.

BACKGROUND: Post-coronovirus disease (COVID) symptoms can persist several months after severe acute respiratory syndrome coronavirus 2 infection. Little is known, however, about the prevalence of post-COVID condition following infections from Omicron variants and how this varies according to vaccination status. This study evaluates the prevalence of symptoms and functional impairment 12 weeks after an infection by Omicron variants (BA.1 and BA.2) compared with negative controls tested during the same period. METHODS: Outpatient individuals who tested positive or negative for COVID-19 infection between December 2021 and February 2022 at the Geneva University Hospitals were followed 12 weeks after their test date. RESULTS: Overall, 11.7% of Omicron cases had symptoms 12 weeks after the infection compared with 10.4% of individuals who tested negative during the same period (P < .001), and symptoms were much less common in vaccinated versus nonvaccinated individuals with Omicron infection (9.7% vs 18.1%; P < .001). There were no significant differences in functional impairment at 12 weeks between Omicron cases and negative controls, even after adjusting for multiple potential confounders. CONCLUSIONS: The differential prevalence of post-COVID symptoms and functional impairment attributed to Omicron BA.1 and BA.2 infection is low when compared with negative controls. Vaccination is associated with lower prevalence of post-COVID symptoms.

Ninety-day outcome of patients with severe COVID-19 treated with tocilizumab - a single centre cohort study.

OBJECTIVES: Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS: In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation <93%, respiratory rate >30/min, C-reactive protein levels >75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS: Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS: In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351503.

Perceptions of vaccination certificates among the general population in Geneva, Switzerland.

OBJECTIVE: This study aimed to assess the public perception of COVID-19 vaccination certificates as well as potential differences between individuals. METHODS: Between 17 March and 1 April 2021, a self-administered online questionnaire was proposed to all persons aged 18 years and older participating in the longitudinal follow-up of SARS-CoV-2 seroprevalence studies in Geneva, Switzerland. The questionnaire covered aspects of individual and collective benefits, and allowed participants to select contexts in which vaccination certificates should be presented. Results were presented as the proportion of persons agreeing or disagreeing with the implementation of vaccination certificates, selecting specific contexts where certificates should be presented, and agreeing or disagreeing with the potential risks related to certificates. Logistic regression was used to calculate odds ratios for factors associated with certificate non-acceptance. RESULTS: Overall, 4067 individuals completed the questionnaire (response rate 77.4%; mean age 53.3 ± standard deviation 14.4 years; 56.1% were women). About 61.0% of participants agreed or strongly agreed that a vaccination certificate was necessary in certain contexts and 21.6% believed there was no context where vaccination certificates should be presented. Contexts where a majority of participants perceived a vaccination certificate should be presented included jobs where others would be at risk of COVID-related complications (60.7%), jobs where employees would be at risk of getting infected (58.7%), or to be exempt from quarantine when travelling abroad (56.0%). Contexts where fewer individuals perceived the need for vaccination certificates to be presented were participation in large gatherings (36.9%), access to social venues (35.5%), or sharing the same workspace (21.5%). Younger age, no intent for vaccination, and not believing vaccination to be an important step in surmounting the pandemic were factors associated with certificate non-acceptance. CONCLUSION: This large population-based study showed that the general adult population in Geneva, Switzerland, agreed with the implementation of vaccination certificates in work-related and travel-related contexts. However, this solution was perceived as unnecessary for access to large gatherings or social venues, or to share the same workspace. Differences were seen with age, sex, education, socioeconomic status, and vaccination willingness and perception, highlighting the importance of taking personal and sociodemographic variation into consideration when predicting acceptance of such certificates.

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.

A population-based serological study of post-COVID syndrome prevalence and risk factors in children and adolescents.

Post-COVID syndrome remains poorly studied in children and adolescents. Here, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Children from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), aged 6 months to 17 years, were tested for anti-SARS-CoV-2 N antibodies (December 2021-February 2022) and parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID. Of 1034 children tested, 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 (ΔaPrev) of 4.1% (95%CI: 1.1;7.3). Stratifying per age group, only adolescents displayed a substantial risk of having post-COVID symptoms (ΔaPrev = 8.3%, 95%CI: 3.5;13.5). Identified risk factors for post-COVID syndrome were older age, having a lower socioeconomic status and suffering from chronic health conditions, especially asthma. Our findings show that a significant proportion of seropositive children, particularly adolescents, experienced persistent COVID symptoms. While there is a need for further investigations, growing evidence of pediatric post-COVID urges early screening and primary care management.

SARS-CoV-2 seroprevalence study after the first wave among persons living and working in an overcrowded Swiss prison.

PURPOSE: Prisons can be epicentres of infectious diseases. However, empirical evidence on the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in prison is still scarce. This study aims to estimate the seroprevalence rates of anti-SARS-CoV-2 in the largest and most crowded Swiss prison and compare them with the seroprevalence rate in the general population. DESIGN/METHODOLOGY/APPROACH: A cross-sectional study was conducted in June 2020, one month after the first wave of SARS-CoV-2 in Switzerland. Groups included: people living in detention (PLDs) detained before the beginning of the pandemic (n = 116), PLDs incarcerated after the beginning of the pandemic (n = 61), prison staff and prison healthcare workers (n = 227) and a sample from the general population in the same time period (n = 3,404). The authors assessed anti-SARS-CoV-2 IgG antibodies. FINDINGS: PLDs who were incarcerated before the beginning of the pandemic had a significantly lower seroprevalence rate [0.9%, confidence interval (CI)95%: 0.1%-5.9%] compared to the general population (6.3%, CI 95%: 5.6-7.3%) (p = 0.041). The differences between PLDs who were incarcerated before and other groups were marginally significant (PLDs incarcerated after the beginning of the pandemic: 6.6%, CI 95%: 2.5%-16.6%, p = 0.063; prison staff CI 95%: 4.8%, 2.7%-8.6%, p = 0.093). The seroprevalence of prison staff was only slightly and non-significantly lower than that of the general population. ORIGINALITY/VALUE: During the first wave, despite overcrowding and interaction with the community, the prison was not a hotspot of SARS-CoV-2 infection. Preventive measures probably helped avoiding clusters of infection. The authors suggest that preventive measures that impact social welfare could be relaxed when overall circulation in the community is low to prevent the negative impact of isolation.

Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting.

SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression related to a decrease in the efficiency of the -1 programmed ribosomal frameshift (PRF) signal of SARS-CoV-2. Using in silico modeling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.

Characteristics of long COVID among older adults: a cross-sectional study.

OBJECTIVE: To describe long-COVID symptoms among older adults, and to assess risk factors for two common long-COVID symptoms: fatigue and dyspnea. METHODS: Multicenter prospective cohort study, conducted in Israel, Switzerland, Spain, and Italy. Included were individuals at least 30 days since COVID-19 diagnosis. We compared long-COVID symptoms between elderly individuals (age>65 years) and younger population (18-65 years); and conducted univariate and multivariable analyses for predictors of long-COVID fatigue and dyspnea. RESULTS: 2333 individuals were evaluated at an average of 5 months [146 days (95% CI 142-150)] following COVID-19 onset. Mean age was 51 and 20.5% were>65 years. Older adults were more likely to be symptomatic, with most common symptoms being fatigue (38%) and dyspnea (30%). They were more likely to complain of cough and arthralgia, and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor. CONCLUSIONS: Older individuals with long-COVID, have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients. RESULTS: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients. DISCUSSION: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

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.

Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs.

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.

Analytical Sensitivity of Eight Different SARS-CoV-2 Antigen-Detecting Rapid Tests for Omicron-BA.1 Variant.

The emergence of each novel SARS-CoV-2 variant of concern (VOC) requires investigation of its potential impact on the performance of diagnostic tests in use, including antigen-detecting rapid diagnostic tests (Ag-RDTs). Although anecdotal reports have been circulating that the newly emerged Omicron-BA.1 variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. We have performed (i) analytical sensitivity testing with cultured virus in eight Ag-RDTs and (ii) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron-BA.1 (n = 59) or Delta (n = 54) breakthrough infection on seven Ag-RDTs. Overall, in our analytical study we have found heterogenicity between Ag-RDTs for detecting Omicron-BA.1. When using cultured virus, we observed a trend toward lower endpoint sensitivity for Omicron-BA.1 detection than for earlier circulating SARS-CoV-2 and the other VOCs. In our retrospective study, the detection of Delta and Omicron-BA.1 was assessed in a comparable set of stored clinical samples using seven Ag-RDTs. Four hundred ninety-seven of all 826 tests (60.17%) performed on Omicron-BA.1 samples were positive, compared to 489/756 (64.68%) for Delta samples. In the analytical study, the sensitivity for both Omicron-BA.1 and Delta between the Ag-RDTs was variable. All seven Ag-RDTs showed comparable sensitivities to detect Omicron-BA.1 and Delta in the retrospective study. IMPORTANCE Sensitivity for detecting Omicron-BA.1 shows high heterogenicity between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. Analytical and retrospective testing is a proxy and timely solution to generate rapid performance data, but it is not a replacement for clinical evaluations, which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

Feasibility of home-based ELISA capillary blood self-testing for anti-SARS-CoV-2 antibodies.

Objectives: Serological assays for the presence of anti-SARS-CoV-2 antibodies are crucially needed for research and monitoring of the SARS-CoV-2 pandemic. Antibodies are reliability detected in capillary blood, a minimally invasive and cost-effective alternative to venous blood testing. However, there is a limited knowledge on feasibility of capillary blood self-sampling. This study compared the feasibility of capillary blood self-testing in people aged less than 65 vs. people aged 65 or more. A secondary aim was to investigate the performance of the Hem-Col® (no additive) device compared to venous blood testing. Design and methods: Data were collected in a prospective study in Switzerland (n = 106). Capillary blood was collected using the Hem-Col® (no additive) device. Feasibility was assessed using 1) collecting the recommended amount of capillary blood and 2) achieving all steps of capillary blood collection. A sample of 5 ml of venous blood was also collected. Results: For the primary objective, 86.2%/62.1% of patients aged less than 65 collected the recommended amount of capillary blood/achieved all steps vs. 62.5%/39.6% of patients aged 65 or more (p = .006/p = .022). For the secondary objective, the correlation between capillary and venous blood was r = 0.992 and kappa = 1. Conclusions: Capillary blood self-testing appeared as a feasible and reliable alternative to venous blood testing. Such alternative would improve access to serological testing and spare health care resources. However, the difference between age groups should be considered when using self-sampling devices. Help should be developed for older people, such as phone counseling or encouraging asking younger family members for help.