Distinct phenotype of SARS-CoV-2 Omicron BA.1 in human primary cells but no increased host range in cell lines of putative mammalian reservoir species

SARS-CoV-2s genetic plasticity has led to several variants of concern (VOCs). Here we studied replicative capacity for seven SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, and Omicron BA.1) in primary reconstituted airway epithelia (HAE) and lung-derived cell lines. Furthermore, to investigate the host range of Delta and Omicron compared to ancestral SARS-CoV-2, we assessed replication in 17 cell lines from 11 non-primate mammalian species, including bats, rodents, insectivores and carnivores. Only Omicrons phenotype differed in vitro, with rapid but short replication and efficient production of infectious virus in nasal HAEs, in contrast to other VOCs, but not in lung cell lines. No increased infection efficiency for other species was observed, but Delta and Omicron infection efficiency was increased in A549 cells. Notably replication in A549 and Calu3 cells was lower than in nasal HAE. Our results suggest better adaptation of VOCs towards humans, without an extended host range.

Clinical sensitivity and specificity of a high-throughput microfluidic nano-immunoassay combined with capillary blood microsampling for the identification of anti-SARS-CoV-2 Spike IgG serostatus

BackgroundWe evaluate the diagnostic performance of dried blood microsampling combined with a high-throughput microfluidic nano-immunoassay (NIA) for the identification of anti-SARS-CoV-2 Spike IgG seropositivity. MethodsWe conducted a serological study among 192 individuals with documented prior SARS-CoV-2 infection and 44 SARS-CoV-2 negative individuals. Participants with prior SARS-CoV-2 infection had a long interval of 11 months since their qRT-PCR positive test. Serum was obtained after venipuncture and tested with an automated electrochemiluminescence anti-SARS-CoV-2 S total Ig reference assay, a commercial ELISA anti-S1 IgG assay, and the index test NIA. 109 participants from the positive cohort and 44 participants from the negative cohort also participated in capillary blood collection using three microsampling devices: Mitra, repurposed glucose test strips, and HemaXis. Samples were dried, shipped by regular mail, extracted, and measured with NIA. FindingsUsing serum samples, we achieve a clinical sensitivity of 98{middle dot}33% and specificity of 97{middle dot}62% on NIA, affirming the high performance of NIA in participants 11 months post infection. Combining microsampling with NIA, we obtain a clinical sensitivity of 95{middle dot}05% using Mitra, 61{middle dot}11% using glucose test strips, 83{middle dot}16% using HemaXis, and 91{middle dot}49% for HemaXis after automated extraction, without any drop in specificity. InterpretationHigh sensitivity and specificity was demonstrated when testing micro-volume capillary dried blood samples using NIA, which is expected to facilitate its use in large-scale studies using home-based sampling or samples collected in the field. FundingSwiss National Science Foundation NRP 78 Covid-19 grant 198412 and Private Foundation of the Geneva University Hospital. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSerological surveillance is of importance to better understand the evolution and spread of SARS-CoV-2 and adapt public health measures. We identified multiple studies conducting such serological surveys using decentralized collection of capillary blood, facilitating the logistics and reducing burden on participants and healthcare facilities. To perform the detection of anti-SARS-CoV-2 antibodies with a high-throughput and at low-cost, a microfluidic nano-immunoassay (NIA) was developed which requires ultra-low sample volumes and minimizes reagent consumption. Added value of this studyIn this study we showed the possibility of combining capillary microsampling with NIA. We validated the use of NIA in serum samples obtained 11 months after infection and show the good clinical performance of the assay in samples with waning antibody titers. Using three different microsampling device, namely Mitra, repurposed glucose test strips, and HemaXis, we implemented a protocol using dried blood sample collection, shipping, extraction, and testing on the microfluidic assay. The sensitivity and specificity were measured and are presented when using the different microsampling devices. Implications of all the available evidenceWe show that the performance of NIA is good when using serum samples, but also in combination with microsampling. Facilitated logistics and increased convenience of microsampling, together with high-throughput and low-cost testing on a microfluidic assay should facilitate the conduction of serological surveys.

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

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

Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron

BackgroundViral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine-breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance. MethodsWe assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed IVTs during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18). FindingsCorrelation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. Vaccinated Delta infected individuals had significantly lower RNA genome copies and IVTs compared to unvaccinated subjects and cleared virus faster. In addition, vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections. InterpretationQuantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine-breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron. FundingThis work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privee des Hopitaux Universitaires de Geneve.

Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants

Emerging SARS-CoV-2 variants of concern/interest (VOC/VOI) raise questions about effectiveness of neutralizing antibodies derived from infection or vaccination. As the population immunity to SARS-CoV-2 has become more complex due to prior infection and/or vaccination, understanding the antigenic relationship between variants is needed. Here, we have assessed in total 104 blood specimens from convalescent individuals after infection with early-pandemic SARS-CoV-2 (pre-VOC) or with Alpha, Beta, Gamma or Delta, post-vaccination after double-dose mRNA-vaccination and break through infections due to Delta or Omicron. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, Omicron) was assessed by plaque-reduction neutralization assay. We found highest neutralization titers against the homologous (previously infecting) variant, with lower neutralization efficiency against heterologous variants. Significant loss of neutralization for Omicron was observed but to a varying degree depending on previously infecting variant (23.0-fold in Beta-convalescence up to 56.1-fold in Alpha-convalescence), suggesting that infection-derived immunity varies, but independent of the infecting variant is only poorly protective against Omicron. Of note, Zeta VOI showed also pronounced escape from neutralization of up to 28.2-fold in Alpha convalescent samples. Antigenic mapping reveals both Zeta and Omicron as separate antigenic clusters. Double dose vaccination showed robust neutralization for Alpha, Beta, Gamma, Delta and Zeta, with fold-change reduction of only 2.8 (for Alpha) up to 6.9 (for Beta). Escape from neutralization for Zeta was largely restored in vaccinated individuals, while Omicron still showed a loss of neutralization of 85.7-fold compared to pre-VOC SARS-CoV-2. Combined immunity from infection followed by vaccination or vaccine breakthrough infection showed highest titers and most robust neutralization for heterologous variants. Breakthrough infection with Delta showed only 12.5-fold reduced neutralization for Omicron, while breakthrough infection with Omicron showed only a 1.5-fold loss for Delta, suggests that infection with antigenically different variants can boost immunity for antigens closer to the vaccine strain. Antigenic cartography showed also a tendency towards broader neutralizing capacity for heterologous variants. We conclude that the complexity of background immunity needs to be taken into account when assessing new VOCs. Development towards separate serotypes such as Zeta was already observed before Omicron emergence, thus other factors than just immune escape must contribute to Omicrons rapid dominance. However, combined infection/vaccination immunity could ultimately lead to broad neutralizing capacity also against non-homologous variants.

Analytical sensitivity of seven SARS-CoV-2 antigen-detecting rapid tests for Omicron variant

BackgroundThe emergence of each novel SARS-CoV-2 variants of concern (VOCs) requires investigation of its potential impact on the performance of diagnostic tests in use, including Antigen-detecting rapid diagnostic tests (Ag-RDT). Although anecdotal reports have been circulating that the newly emerged Omicron variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. MethodsWe have performed 1) analytical sensitivity testing with cultured virus in eight Ag-RDTs and 2) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron (n=18) or Delta (n=17) breakthrough infection on seven Ag-RDTs. FindingsOverall, we have found large heterogenicity between Ag-RDTs for detecting Omicron. When using cultured virus, we observed a trend towards lower sensitivity for Omicron detection compared to earlier circulating SARS-CoV-2 and the other VOCs. When comparing performance for Delta and Omicron in a comparable set of clinical samples in seven Ag-RDTs, 124/252 (49.2%) of all test performed showed a positive result for Omicron compared to 156/238 (65.6%) for Delta samples. Sensitivity for both Omicron and Delta between Ag-RDTs was highly variable. Four out of seven Ag-RDTs showed significantly lower sensitivity (p<0.001) to detect Omicron when compared to Delta while three had comparable sensitivity to Delta. InterpretationSensitivity for detecting Omicron is highly variable between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. While analytical and retrospective testing may be a proxy and timely solution to generate performance data, 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. FundingThis work was supported by the Swiss National Science Foundation (grant numbers 196383, 196644 and 198412), the Fondation Ancrage Bienfaisance du Groupe Pictet, the Fondation Privee des Hopiteaux Universitaires de Geneve and FIND, the global alliance for diagnostics.

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

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.

Analytical performance of eleven SARS-CoV-2 antigen-detecting rapid tests for Delta variant

Global concerns arose as the emerged and rapidly spreading SARS-CoV-2 Delta variant. To date, few data on routine diagnostic performance for Delta are available. Here, we investigate the analytical performance of eleven commercially available antigen-detecting rapid diagnostic tests (Ag-RDTs) for Delta VOC in comparison with current and earlier VOCs (Alpha, Beta and Gamma) and early pandemic variant using cultured SARS-CoV-2. Comparable sensitivity was observed for Delta for the majority of Ag-RDTs.

Analytical comparison of nine SARS-CoV-2 antigen-detecting rapid diagnostic tests for emerging SARS-CoV-2 variants

Several SARS-CoV-2 variants of concern/interest (VOC/VOI) emerged recently, with VOCs outcompeting earlier lineages on a global scale. To date, few data on routine diagnostic performance for VOC/VOIs are available. Here, we investigate the analytical performance of nine commercially available antigen-detecting rapid diagnostic tests (Ag-RDTs) for VOC B.1.1.7, B.1.351, P.1 and VOI P.2 with cultured SARS-CoV-2. Comparable or higher sensitivity was observed for VOC/VOI compared to a non-VOC/VOI early-pandemic virus for all Ag-RDTs.

Assessment of the infectious threshold of SARS-CoV-2 in primary airway epithelial cells

Comparison of virus isolation success from clinical samples across a range of viral loads inoculated in parallel on Vero E6 and human airway epithelia (HAE) showed lower success of virus isolation in HAE, suggesting an overestimation of actual infectiousness in humans using Vero E6 cell lines, commonly considered as reference.

SARS-CoV-2 infections in nasal epithelial cells from smokers versus non-smokers

Whether smoking exacerbates Coronavirus disease 2019 is still debated. Ex-vivo Infection of reconstituted epithelial tissues from smoker versus non-smoker donors suggested comparable susceptibility to SARS-CoV-2 in epithelia from both groups.

Diagnostic accuracy of SARS-CoV-2 rapid antigen detection testing in symptomatic and asymptomatic children in the clinical setting

ImportanceAntigen-based rapid diagnostic tests (RDTs) have shown good sensitivity for SARS-CoV-2 detection in adults and are used in children despite the lack data from children. ObjectiveWe evaluated the diagnostic performance of the Panbio-COVID-19 Ag Rapid Test Device (P-RDT) in symptomatic and asymptomatic children against reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs (NPS). DesignProspective diagnostic study from 11.2020 to 03.2021. SettingSingle-center. ParticipantsConsecutive symptomatic and asymptomatic participants 0-16yo. InterventionTwo NPS for both RT-PCR and P-RDT. Main outcomeP-RDT sensitivity and specificity. ResultsEight-hundred and twenty-two participants completed the study, of which 533 (64.9%) were symptomatic. Among the 119 (14.5%) RT-PCR positive patients, the overall P-RDT sensitivity was 0.66 (95%CI 0.57-0.74). Mean viral load (VL) was higher among P-RDT positive than negative ones (p<0.001). Sensitivity was 0.87 in specimens with VL>1.0E6 copies/mL (95%CI 0.87-1.00), which is the accepted cut-off for the presence of infectious virus, and decreased to 0.67 (95%CI 0.59-0.76) for specimens >1.0E3 copies/mL. Among symptomatic participants, the P-RDT displayed a sensitivity of 0.73 (95%CI 0.64-0.82), which peaked at 1.00 at 2 days post onset of symptoms (DPOS; 95%CI 1.00-1.00), then decreased to 0.56 (95%CI 0.23-0.88) at 5 DPOS. There was a trend towards lower P-RDT sensitivity in symptomatic children <12 years (0.62 [95%CI 0.45-0.78]) versus [≥]12 years (0.80 [95%CI 0.69-0.91]; p=0.09). VL which was significantly lower in asymptomatic participants than in symptomatic ones (p<0.001). The P-RDT displayed a sensitivity of 0.43 (95%CI 0.26-0.61). Specificity was 1.00 in symptomatic and asymptomatic children (95%CI 0.99-1.00). Conclusion and relevanceThe overall respective 73% and 43% sensitivities of P-RDT in symptomatic and asymptomatic children was below the 80% cut-off recommended by the World Health Organization. These findings are likely explained by lower VLs in children at the time of diagnosis. As expected, we observed a direct correlation between VL and P-RDT sensitivity as well as variation of sensitivity according to DPOS, a major determinant of VL. These data highlight the limitations of RDTs both in symptomatic and asymptomatic children, with the potential exception in early symptomatic children [≥]12yrs where sensitivity reached 80%.

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

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.

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland

BackgroundIn December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.7. Based on initial data from the UK and later data from other countries, this variant was estimated to have a transmission fitness advantage of around 40-80% [1, 2, 3]. AimThis study aims to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time based on data from Switzerland. MethodsWe generated whole genome sequences from 11.8% of all confirmed SARS-CoV-2 cases in Switzerland between 14 December 2020 and 11 March 2021. Based on these data, we determine the daily frequency of the B.1.1.7 variant and quantify the variants transmission fitness advantage on a national and a regional scale. ResultsWe estimate B.1.1.7 had a transmission fitness advantage of 43-52% compared to the other variants circulating in Switzerland during the study period. Further, we estimate B.1.1.7 had a reproductive number above 1 from 01 January 2021 until the end of the study period, compared to below 1 for the other variants. Specifically, we estimate the reproductive number for B.1.1.7 was 1.24 [1.07-1.41] from 01 January until 17 January 2021 and 1.18 [1.06-1.30] from 18 January until 01 March 2021 based on the whole genome sequencing data. From 10 March to 16 March 2021, once B.1.1.7 was dominant, we estimate the reproductive number was 1.14 [1.00-1.26] based on all confirmed cases. For reference, Switzerland applied more non-pharmaceutical interventions to combat SARS-CoV-2 on 18 January 2021 and lifted some measures again on 01 March 2021. ConclusionThe observed increase in B.1.1.7 frequency in Switzerland during the study period is as expected based on observations in the UK. In absolute numbers, B.1.1.7 increased exponentially with an estimated doubling time of around 2-3.5 weeks. To monitor the ongoing spread of B.1.1.7, our plots are available online.

SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

AimsUnravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining i) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response, ii) their relationship to prognosis, and iii) the degree of linear homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes. Methods and ResultsImmunoreactivity against different engineered peptides as well as cytokines were assessed by immunoassays, on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Using bioinformatics modelling a linear sequence homologies between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. ConclusionCOVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

Diagnostic accuracy of PanbioTM rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2

BackgroundAntigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. MethodsWe conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS. Results402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values [≤] 26.7 ([≥] 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. InterpretationBased on our findings, the diagnostic performance of the Panbio Covid-19 RDT with OPS samples meet the criteria required by the WHO for Ag-RDTs (sensitivity[≥]80% and specificity [≥]97%).

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

BackgroundPopulation-based serological surveys provide a means for assessing the immunologic landscape of a community, without the biases related to health-seeking behaviors and testing practices typically associated with rt-PCR testing. This study assesses SARS-CoV-2 seroprevalence over the first epidemic wave in Canton Geneva, Switzerland, as well as biological and socio-economic risk factors for infection and symptoms associated with IgG seropositivity. Methods and findingsBetween April 6 and June 30, 2020, former participants of a yearly representative cross-sectional survey of the 20-75-year-old population of the canton of Geneva were invited to participate in a seroprevalence study, along with household members five years and older. We collected blood and tested it for anti-SARS-CoV-2 immunoglobulins G (IgG). Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. We included 8344 participants (53.5% women, mean age 46.9 years). The population-level seroprevalence over the 12-week study period was 7.8 % (95% Credible Interval (CrI) 6.8-8.9), accounting for sex, age and household random effects. Seroprevalence was highest among 18-49 year olds (9.5%, 95%CrI 8.1-10.9), with young children (5-9 years) and those >65 years having significantly lower seroprevalence (4.3% and 4.7-5.4% respectively). Men were more likely to be seropositive than women (relative risk 1.2, 95%CrI 1.1-1.4). Odds of seropositivity were reduced for female retirees (0.46, 95%CI 0.23-0.93) and unemployed men (0.35, 95%CI 0.13-1.0) compared to employed individuals, and for current smokers (0.36, 95%CI 0.23-0.55) compared to never-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. Symptoms most strongly associated with seropositivity were anosmia/dysgeusia, loss of appetite, fever, fatigue and myalgia and/or arthralgia. Thirteen percent of seropositive participants reported no symptoms. ConclusionsOur results confirm a low population seroprevalence of anti-SARS-CoV-2 antibodies after the first wave in Geneva, a region hard hit by the COVID-19 pandemic. Socioeconomic factors were not associated with seropositivity in this sample. The elderly and young children were less frequently seropositive, though it is not clear how biology and behaviors shape these differences. These specificities should be considered when assessing the need for targeted public health measures.

Diagnostic accuracy of two commercial SARS-CoV-2 Antigen-detecting rapid tests at the point of care in community-based testing centers

BackgroundAntigen-detecting rapid diagnostic tests for SARS-CoV-2 offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. MethodsWe performed a prospective, single-center, point of care validation of two antigen-detecting rapid diagnostic tests (Ag-RDT) in comparison to RT-PCR on nasopharyngeal swabs. FindingsBetween October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioCovid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. InterpretationWe provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of [≥]80% sensitivity and [≥]97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value. FundingFoundation of Innovative Diagnostics (FIND), Fondation privee des HUG, Pictet Charitable Foundation.

Household Transmission of SARS-COV-2: Insights from a Population-based Serological Survey

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.