Risk factors for household transmission of SARS-Cov-2: a modelling study in the French national population-based EpiCov cohort

BackgroundHouseholds are specific transmission settings, as they involve close and repeated contacts between individuals of different generations. Household surveys provide a unique opportunity to better understand SARS-CoV-2 transmission and the role of individual characteristics. Here, we assessed the risk of SARS-CoV-2 acquisition from household and community exposure according to age, family ties, and socioeconomic and living conditions using data from the nationwide population-based EpiCov cohort/ORCHESTRA collaboration in November-December 2020. MethodsA history of SARS-CoV-2 infection was defined by a positive Euroimmun Anti-SARS-CoV-2 ELISA IgG result in November-December 2020. We applied stochastic chain binomial models fitted to the final distribution of infections in households to data from 17,983 individuals [≥]5 years enrolled from 8,165 households. Models estimated the competing risks of being infected from community and household exposure. ResultsYoung adults aged 18-24 years had the highest risk of extra-household infection (8.9%, [95% credible interval, Crl]: 7.5 - 10.4), whereas the oldest (>75) and the youngest (6-10) had the lowest risk, 2.6% (1.8 - 3.5) and 3.4% (1.9 - 5.2), respectively. Extra-household infection was also independently associated with socioeconomic conditions. Within households, the probability of person-to-person transmission increased with age: 10.6% (5.0 - 17.9) among 6-10-year-olds to 43.1% (32.6 - 53.2) among 65-74-year-olds. It was higher between partners 29.9% (25.6 - 34.3) and from mother to child 29.1% (21.4 - 37.3) than between individuals related by other family ties. ConclusionIn 2020 in France, the main factors identified for extra-household infection were age and socioeconomic conditions. Intra-household infection mainly depended on age and family ties. Key MessagesO_LIYoung adults aged 18-24 years had the highest probability of extra-household SARS-Cov-2 acquisition over the year 2020: 8.9%, 95% credible interval (95%Crl) 7.5 - 10.4. C_LIO_LIThe probability of extra-household infection increased with family income and population density in the municipality of residence and was higher in the French regions most affected by the waves of SARS-CoV-2. C_LIO_LIWhen estimating the probability of person-to-person transmission of SARS-CoV-2, the 65-74 year-olds had the highest susceptibility, i.e. the highest probability of SARS-CoV-2 acquisition when exposed to an infected household member (22.1%, 16.4 - 28.2) C_LIO_LIThe probability of transmission was the highest between partners (29.9%, 25.6 - 34.3). The probability of transmission was higher from mother to child than from father to child: 29.1%, (21.4 - 37.3) and 14.0% (5.9 - 22.8), respectively. The probability of transmission from child to parent was higher from children <12 years than for older children: 11.8% (2.5 - 25.1) and 4.1% (0.9 - 9.0), respectively. C_LI

Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial

Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. The CORIPLASM study was an open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19, including immunocompromised patients. Patients hospitalised with COVID-19 and less than 9 days since symptoms onset were assigned to receive 4 units of plasma over 2 days ({approx} 840 ml)(CCP) or usual care alone (UC). Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) [≥]6 on the 10-point scale on day (d) 4 and survival without ventilation or additional immunomodulatory treatment by d14. A total of 120 patients were recruited and assigned to CCP (n=60) or UC (n=60), including 22 (CCP) and 27 (UC) immunocompromised patients. Thirteen (22%) patients with CCP had a WHO-CPS [≥]6 at d4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95%CI 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0{middle dot}10 -1{middle dot}53]), and 7 (12%) with CCP and 12 (20%) with UC at d28 (aHR 0.51 [95%CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in immunocompromised patients (HR 0.37 [95%CI 0.14-0.97]). CCP treatment did not improve early outcomes in patients with moderate COVID-19 but was associated with reduced mortality in the subgroup of immunocompromised patients.

SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021

We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that [~]15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.

Immunogenicity and Safety of Beta Adjuvanted Recombinant Booster Vaccine

BackgroundVariant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response. MethodsIn this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a [≥]10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15. FindingsThe percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor [≥]10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines. InterpretationHeterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants. FundingFrench Ministries of Solidarity and Health and Research and Sanofi Trial registration numberClinicalTrials.gov identifier NCT05124171; EudraCT identifier 2021-004550-33.

Biosynthetic proteins targeting the SARS-CoV-2 spike as anti-virals

The binding of the SARS-CoV-2 spike to angiotensin-converting enzyme 2 (ACE2) promotes virus entry into the cell. Targeting this interaction represents a promising strategy to generate antivirals. By screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal HEAT-like scaffold (named Reps), we selected candidates recognizing the spike receptor binding domain (RBD). Two of them (F9 and C2) bind the RBD with affinities in the nM range, displaying neutralisation activity in vitro and recognizing distinct sites, F9 overlapping the ACE2 binding motif. The F9-C2 fusion protein and a trivalent Rep form (C2-foldon) display 0.1 nM affinities and EC50 of 8-18 nM for neutralization of SARS-CoV-2. In hamsters, F9-C2 instillation in the nasal cavity before or during infections effectively reduced the replication of a SARS-CoV-2 strain harbouring the D614G mutation in the nasal epithelium. Furthermore, F9-C2 and/or C2-foldon effectively neutralized SARS-CoV-2 variants (including delta and omicron variants) with EC50 values ranging from 13 to 32 nM. With their high stability and their high potency against SARS-CoV-2 variants, Reps provide a promising tool for SARS-CoV-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment. Author SummaryThe entry of SARS-CoV-2 in permissive cells is mediated by the binding of its spike to angiotensin-converting enzyme 2 (ACE2) on the cell surface. To select ligands able to block this interaction, we screened a library of phages encoding artificial proteins (named Reps) for binding to its receptor binding domain (RBD). Two of them were able to bind the RBD with high affinity and block efficiently the virus entry in cultured cells. Assembled Reps through covalent or non-covalent linkages blocked virus entry at lower concentration than their precursors (with around 20-fold activity increase for a trimeric Rep). These Reps derivates neutralize efficiently SARS-CoV-2 {beta}, {gamma}, {delta} and Omicron virus variants. Instillation of an Rep dimer in the nasal cavity effectively reduced virus replication in the hamster model of SARS-CoV-2 and pathogenicity.

Humoral response, associated symptoms and profile of patients infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

ObjectivesTaste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and humoral response intensity associated with taste or smell disorders. Patients and methodsWe used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. ResultsThe analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. ConclusionAmong patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with a humoral response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate

The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.

Pre-clinical evaluation of antiviral activity of nitazoxanide against Sars-CoV-2

To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2. First, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against SARS-CoV-2. Then, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. In a SARS-CoV-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. We hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. Indeed, our pharmacokinetic study confirmed that concentrations of tizoxanide in organs of interest were always below the in vitro EC50. These preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for Covid-19.

Trends in social exposure to SARS-Cov-2 in France. Evidence from the national socio-epidemiological cohort - EPICOV

BackgroundWe aimed to study whether social patterns of exposure to SARS-CoV-2 infection changed in France throughout the year 2020, in light to the easing of social contact restrictions. MethodsA population-based cohort of individuals aged 15 years or over was randomly selected from the national tax register to collect socio-economic data, migration history, and living conditions in May and November 2020. Home self-sampling on dried blood was proposed to a 10% random subsample in May and to all in November. A positive anti-SARS-CoV-2 ELISA IgG result against the virus spike protein (ELISA-S) was the primary outcome. The design, including sampling and post-stratification weights, was taken into account in univariate and multivariate analyses. ResultsOf the 134,391 participants in May, 107,759 completed the second questionnaire in November, and respectively 12,114 and 63,524 were tested. The national ELISA-S seroprevalence was 4.5% [95%CI: 4.0%-5.1%] in May and 6.2% [5.9%-6.6%] in November. It increased markedly in 18-24-year-old population from 4.8% to 10.0%, and among second-generation immigrants from outside Europe from 5.9% to 14.4%. This group remained strongly associated with seropositivity in November, after controlling for any contextual or individual variables, with an adjusted OR of 2.1 [1.7-2.7], compared to the majority population. In both periods, seroprevalence remained higher in healthcare professions than in other occupations. ConclusionThe risk of Covid-19 infection increased among young people and second-generation migrants between the first and second epidemic waves, in a context of less strict social restrictions, which seems to have reinforced territorialized socialization among peers.

Endonuclease-based genotyping of the RBM, a first-line method for the surveillance of emergence or evolution of SARS-CoV-2 Variants.

Since the beginning of the Covid-19 pandemics, variants have emerged. Whereas most of them have no to limited selective advantage, some display increased transmissibility and/or resistance to immune response. To date, most of the mutations involved in the functional adaptation are found in the Receptor Binding Module (RBM), close to the interface with the human receptor ACE2. In this study, we thus developed and validated a fast and simple molecular assay allowing the detection and partial identification of the mutations in the RBM coding sequence. After the amplification of the region of interest, the amplicon is heat-denatured and hybridized with an amplicon of reference. The presence of a mutation in the heteroduplex can be cleaved by a mismatch-specific endonuclease and the cleavage pattern is analysed by capillary electrophoresis. The approach was first validated on viral RNA purified different SARS-CoV-2 variants produced in the lab before being implemented for clinical samples. The results highlighted the performance of the assay for the detection of mutations in the RBM from clinical samples. The procedure can be easily set up for high throughput identification of the presence of mutations and serve as a first-line screening to select the samples for full genome sequencing.

Niclosamide shows strong antiviral activity in a human airway model of SARS-CoV-2 infection and a conserved potency against the UK B.1.1.7 and SA B.1.351 variant

SARS-CoV-2 variants are emerging with potential increased transmissibility highlighting the great unmet medical need for new therapies. Niclosamide is a potent anti-SARS-CoV-2 agent that has advanced in clinical development. We validate the potent antiviral efficacy of niclosamide in a SARS-CoV-2 human airway model. Furthermore, niclosamide is effective against the D614G, B.1.1.7 and B.1.351 variants. Our data further support the potent anti-SARS-CoV-2 properties of niclosamide and highlights its great potential as a therapeutic agent for COVID-19.

SARS-CoV-2 20I/501Y.V1 variant in the hamster model

Late 2020, SARS-CoV-2 Alpha variant from lineage B.1.1.7 emerged in United Kingdom and gradually replaced the G614 strains initially involved in the global spread of the pandemic. In this study, we used a Syrian hamster model to compare a clinical strain of Alpha variant with an ancestral G614 strain. The Alpha variant succeeded to infect animals and to induce a pathology that mimics COVID-19. However, both strains replicated to almost the same level and induced a comparable disease and immune response. A slight fitness advantage was noted for the G614 strain during competition and transmission experiments. These data do not corroborate the epidemiological situation observed during the first half of 2021 in humans nor reports that showed a more rapid replication of Alpha variant in human reconstituted bronchial epithelium.

Replicative fitness SARS-CoV-2 20I/501Y.V1 variant in a human reconstituted bronchial epithelium

Since its emergence in 2019, circulating populations of the new coronavirus continuously acquired genetic diversity. At the end of 2020, a variant named 20I/501Y.V1 (lineage B.1.1.7) emerged and replaced other circulating strains in several regions. This phenomenon has been poorly associated to biological evidence that this variant and original strain exhibit different phenotypic characteristics. Here, we analyse the replication ability of this new variant in different cellular models using for comparison an ancestral D614G European strain (lineage B1). Results from comparative replication kinetics experiments in vitro and in a human reconstituted bronchial epithelium showed no difference. However, when both viruses were put in competition in a human reconstituted bronchial epithelium, the 20I/501Y.V1 variant outcompeted the ancestral strain. Altogether, these findings demonstrate that this new variant replicates more efficiently and could contribute to better understand the progressive replacement of circulating strains by the SARS-CoV-2 20I/501Y.V1 variant. ImportanceThe emergence of several SARS-CoV-2 variants raised numerous questions concerning the future course of the pandemic. We are currently observing a replacement of the circulating viruses by the variant from the United Kingdom known as 20I/501Y.V1 from B.1.1.7 lineage but there is little biological evidence that this new variant exhibit a different phenotype. In the present study, we used different cellular models to assess the replication ability of the 20I/501Y.V1 variant. Our results showed that this variant replicate more efficiently in a human reconstituted bronchial epithelium, which may explain why it spreads so rapidly in human populations.

A national mixed-mode seroprevalence random population-based cohort on SARS-CoV-2 epidemic in France: the socio-epidemiological EpiCov study

Backgroundthe EpiCov study, initiated at the end of the first national lockdown in France, aimed to provide national and regional estimates of the seroprevalence of SARS-CoV-2 infection, and to analyze relations between living conditions and the dynamics of the epidemic. We present and discuss here the survey methodology, and describe the first-round fieldwork. Method371,000 individuals aged 15 years or more were randomly selected from the national tax register, stratified by departments, including three overseas departments, and by poverty level with over-representation of people living below the poverty line. Health, socio-economics, migration history, and living conditions were collected through self-computed-assisted web interviews or via computer-assisted telephone interviews. The first-round survey was conducted in May. A random subsample was eligible to receive material for home blood self-sample on dried blood spot (DBS), in order to detect IgG antibodies against the spike protein (Euroimmun ELISA-S), and neutralizing antibodies for non-negative ELISA-S. For the second-round conducted in November, all respondents were eligible for the antibodies detection from home DBS sample, as well as the other household members aged 6 years or more for 20% of them. Participation and adjustment for nonresponse134,391 respondents completed the first-round questionnaire from May 2 to June 1, 2020, including 16,970 (12.6%) respondents under the poverty line. Multimodal web/tel interviews was randomly assigned to 20% of the sample. The other were assigned to exclusive CAWI. Overall 17,441 respondents were eligible for home blood sample, among them 12,114 returned the DBS (interquartile date: May 25-June 5). The response probability was first estimated from logit models adjusted on a wide range of auxiliary demographic and socio-economic variables available from the sampling frame, and final weights calibrated to the margins of the population census permitted to correct for a large part of the non-response bias. ConclusionThe Epicov study is one of the largest national random population-based seroprevalence cohort, with both an epidemiological and sociological approaches to evaluate the spread of the COVID-19 epidemic, and the impact on health and living conditions. One of the major interests of this study is the broad coverage of the socio-economic and territorial diversity of the population.

Monitoring the proportion infected by SARS-CoV-2 from age-stratified hospitalisation and serological data

BackgroundRegional monitoring of the proportion infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. MethodsWe developed a method to reconstruct in real-time the proportion infected by SARS-CoV-2 and the proportion of infections being detected from the joint analysis of age-stratified seroprevalence, hospitalisation and case data. We applied our approach to the 13 French metropolitan regions. FindingsWe estimate that 5.7% [5.1%-6.4%] of adults in metropolitan France had been infected by SARS-CoV-2 by May 2020. This proportion remained stable until August and increased to 12.6% [11.2%-14.3%] by the end of November. With 23.8% [21.2%-26.8%] infected in the Paris region compared to 4.0% [3.5% - 4.6%] in Brittany, regional variations remained large (Coefficient of Variation CV: 0.53) although less so than in May (CV: 0.74). The proportion infected was twice higher (17.6% [13.4%-22.7%]) in 20-49 y.o. than in 50+ y.o (8.0% [5.7% - 11.5%]). Forty percent [33.7% - 45.4%] of infections in adults were detected in June-August compared to 55.7% [48.7% - 63.1%] in September-November. Our method correctly predicted seroprevalence in 11 regions in which only hospitalisation data were used. InterpretationIn the absence of contemporary serosurvey, our real-time monitoring indicates that the proportion infected by SARS-CoV-2 may be above 20% in some French regions. FundingEU RECOVER, ANR, Fondation pour la Recherche Medicale, Inserm.

Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2

Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19. Here, we present the pre-clinical evaluation of Imatinib in multiple models. Our results indicated that Imatinib and another TKI, the Masitinib, exhibit an antiviral activity in VeroE6 cells. However, Imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, Imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of Imatinib and similar TKIs as antivirals in the treatment of Covid-19.

Ready for a BASE jump? Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population.

Seroprevalence results coupled with surveillance data were used to estimate the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. IHR and IFR were dramatically high in the very elderly (80-90 years: IHR: 30%, IFR: 11%), but also substantial in middle-aged adults (40-50 years: IHR: 1.2%, IFR: 0.05%).

Seroprevalence of SARS-CoV-2 IgG antibodies, in Corsica (France), April and June 2020.

Our aim was to assess the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection after the lockdown in a sample of the Corsican population. Between 16th April and 15th June 2020, 2,312 residual sera were collected from patients having carried out a blood analysis in one of the participating laboratories. Residual sera obtained from persons of all ages were tested for the presence of anti-SARS-CoV-2 IgG using the EUROIMMUN enzyme immunoassay kit for semiquantitative detection of IgG antibodies against S1 domain of viral spike protein (ELISA-S). Borderline and positive samples in ELISA-S were also tested with an in-house virus neutralization test (VNT). Prevalence values were adjusted for sex and age. A total of 1,973 residual sera samples were included in the study. The overall seroprevalence based on ELISA-S was 5.27% [95% confidence interval (CI) 4.33-6.35] and 5.46% [4.51-6.57] after adjustment. Gender was not associated with IgG detection. However, significant differences were observed between age groups (p-value = 1 E-5) and particularly for people being younger than 50 years of age (Odd ratio (OR) = 2.86 95% CI [1.80-4.53]; p-value <0.000001*). The prevalence of neutralizing antibody titers [≥]40 was of 3% [2.28-3.84]. In conclusion the present study showed that a low seroprevalence for COVID-19 in Corsica in accordance with values reported for other French regions in which the impact of the pandemic was low.

Seroprevalence of SARS-CoV-2 among adults in three regions of France following the lockdown and associated risk factors: a multicohort study.

Aim To estimate the seroprevalence of SARS-CoV-2 infection in May-June 2020 after the lockdown in adults living in three regions in France and to identify the associated risk factors. Methods Participants in a survey on COVID-19 from an existing consortium of three general adult population cohorts living in the Ile-de-France (IDF) or Grand Est (GE), two regions with high rate of COVID-19, or in the Nouvelle-Aquitaine (NA), with a low rate, were asked to take a dried-blood spot (DBS) for anti-SARS-CoV-2 antibodies assessment. The primary outcome was a positive anti-SARS-CoV-2 ELISA IgG result against the spike protein of the virus (ELISA-S). The secondary outcomes were a positive ELISA IgG against the nucleocapsid protein (ELISA-NP), anti-SARS-CoV-2 neutralizing antibodies titers >=40 (SN), and predicted positivity obtained from a multiple imputation model (MI). Prevalence estimates were adjusted using sampling weights and post-stratification methods. Findings Between May 4, 2020 and June 23, 2020, 16,000 participants were asked to provide DBS, and 14,628 were included in the analysis, 983 with a positive ELISA-S, 511 with a positive ELISA-NP, 424 with SN>=40 and 941 (Standard Deviation=31) with a positive MI. Adjusted estimates of seroprevalence (positive ELISA-S) were 10.0% (95%CI 9.1%;10.9%) in IDF, 9.0% (95%CI 7.7%; 10.2%) in GE and 3.1% (95%CI 2.4%; 3.7%), in NA. The adjusted prevalence of positive ELISA-NP, SN and MI were 5.7%, 5.0% and 10.0% in IDF, 6.0%, 4.3% and 8.6% in GE, and 0.6%, 1.3% and 2.5% in NA, respectively. A higher seroprevalence was observed in younger participants and when at least one child or adolescent lived in the same household. A lower seroprevalence was observed in smokers compared to non-smokers. Interpretation At the end of the lockdown the prevalence of anti-SARS-CoV-2 IgG or neutralizing antibodies remained low in the French adult population, even in regions with high reported rates of COVID-19.

Favipiravir and severe acute respiratory syndrome coronavirus 2 in hamster model

Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we used a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment was initiated before or simultaneously to infection, favipiravir had a strong dose effect, leading to dramatic reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlated with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. The antiviral efficacy observed in this study was achieved with plasma drug exposure comparable with those previously found during human clinical trials and was associated with weight losses in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.