Source of SARS-CoV-2 infection: results from a series of 584,846 cases in France from October 2020 to August 2022.

BACKGROUND: We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France. METHODS: Participants from the nationwide ComCor case-control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection. RESULTS: Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection. CONCLUSION: Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

Risk of SARS-CoV-2 Infection Among Households With Children in France, 2020-2022.

Importance: Understanding the contribution of children to SARS-CoV-2 circulation in households is critical for designing public health policies and mitigation strategies. Objective: To identify temporal changes in the risk of SARS-CoV-2 infection in people living with children. Design, Setting, and Participants: This case-control study included online questionnaire responses from French adults between October 2020 and October 2022. Eligible cases were adults with ongoing SARS-CoV-2 infection with an email address on record with the national health insurance system, which centralized all new diagnoses in France. Eligible controls were adults who had never tested positive for SARS-CoV-2 until February 2021, when eligibility was extended to all adults without ongoing SARS-CoV-2 infection. Exposure: Transmission of SARS-CoV-2 from a child (aged under 18 years) within the household in the descriptive analysis, as reported by the participating case. Sharing household with a child (of any age or broken down by school level) in the case-control analysis. Main Outcome and Measures: Ongoing SARS-CoV-2 infection diagnosed by reverse transcription-polymerase chain reaction or supervised rapid antigen test (ie, not self-tests). Results: A total of 682 952 cases were included for the descriptive analysis (68.8% female, median [IQR] age, 44 [34-55] years). Among those, 45 108 (6.6%) identified a household child as the source case; this proportion peaked at 10.4% during the Omicron BA.1 wave (December 20, 2021, to April 8, 2022). For the case-control analysis, we matched 175 688 cases (with a 4:1 ratio) for demographic characteristics with 43 922 controls. In multivariable logistic regression analysis, household exposure to children was associated with an increased risk of infection mainly at the end of summer 2021 (receding Delta wave) and during winter 2022 (Omicron BA.1 wave). In subgroup analysis by school level of the child, living with children under the age of 6 was associated with increased odds of infection throughout the study period, peaking at an odds ratio (OR) 1.8 (95% CI, 1.6-2.1) for children looked after by professional in-home caregivers, 1.7 (95% CI, 1.5-1.7) for children in day care facilities, and 1.6 (95% CI, 1.4-1.8) for children in preschool. The ORs associated with household exposure to children aged 6 to 14 years increased during the Delta (August 14, 2021, to December 19, 2021) and Omicron BA.1 waves, reaching 1.6 (95% CI, 1.5-1.7) for primary school children and 1.4 (95% CI, 1.3-1.5) for middle school children. Exposure to older children aged 15 to 17 years was associated with a moderate risk until April 2021, with an OR of 1.2 (95% CI, 1.2-1.3) during curfew in early 2021 (December 4, 2020, to April 8, 2021). Conclusions and Relevance: The presence of children, notably very young ones, was associated with an increased risk of SARS-CoV-2 infection in other household members, especially during the Delta and Omicron BA.1 waves. These results should help to guide policies targeting children and immunocompromised members of their household.

Reduction of SARS-CoV-2 intra-household child-to-parent transmission associated with ventilation: results from a case-control study.

PURPOSE: Our objective was to describe circumstances of SARS-CoV-2 household transmission and to identify factors associated with a lower risk of transmission in a nationwide case-control study in France. METHODS: In a descriptive analysis, we analysed cases reporting transmission from someone in the household (source case). Index cases could invite a non-infected household member to participate as a related control. In such situations, we compared the exposures of the index case and related control to the source case by conditional logistic regression matched for household, restricted to households in which the source case was a child, and the index case and related control were the infected child's parents. RESULTS: From October 27, 2020 to May 16, 2022, we included 104 373 cases for the descriptive analysis with a documented infection from another household member. The source case was mostly the index case's child (46.9%) or partner (45.7%). In total, 1026 index cases invited a related control to participate in the study. In the case-control analysis, we included 611 parental pairs of cases and controls exposed to the same infected child. COVID-19 vaccination with 3 + doses versus no vaccination (OR 0.1, 95%CI: 0.04-0.4), isolation from the source case (OR 0.6, 95%CI: 0.4-0.97) and the ventilation of indoor areas (OR 0.6, 95%CI: 0.4-0.9) were associated with lower risk of infection. CONCLUSION: Household transmission was common during the SARS-CoV-2 pandemic in France. Mitigation strategies, including isolation and ventilation, decreased the risk of secondary transmission within the household. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022.

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

SARS-CoV-2 incubation period across variants of concern, individual factors, and circumstances of infection in France: a case series analysis from the ComCor study.

BACKGROUND: The incubation period of SARS-CoV-2 has been estimated for the known variants of concern. However, differences in study designs and settings make comparing variants difficult. We aimed to estimate the incubation period for each variant of concern compared with the historical strain within a unique and large study to identify individual factors and circumstances associated with its duration. METHODS: In this case series analysis, we included participants (aged ≥18 years) of the ComCor case-control study in France who had a SARS-CoV-2 diagnosis between Oct 27, 2020, and Feb 4, 2022. Eligible participants were those who had the historical strain or a variant of concern during a single encounter with a known index case who was symptomatic and for whom the incubation period could be established, those who reported doing a reverse-transcription-PCR (RT-PCR) test, and those who were symptomatic by study completion. Sociodemographic and clinical characteristics, exposure information, circumstances of infection, and COVID-19 vaccination details were obtained via an online questionnaire, and variants were established through variant typing after RT-PCR testing or by matching the time that a positive test was reported with the predominance of a specific variant. We used multivariable linear regression to identify factors associated with the duration of the incubation period (defined as the number of days from contact with the index case to symptom onset). FINDINGS: 20 413 participants were eligible for inclusion in this study. Mean incubation period varied across variants: 4·96 days (95% CI 4·90-5·02) for alpha (B.1.1.7), 5·18 days (4·93-5·43) for beta (B.1.351) and gamma (P.1), 4·43 days (4·36-4·49) for delta (B.1.617.2), and 3·61 days (3·55-3·68) for omicron (B.1.1.529) compared with 4·61 days (4·56-4·66) for the historical strain. Participants with omicron had a shorter incubation period than participants with the historical strain (-0·9 days, 95% CI -1·0 to -0·7). The incubation period increased with age (participants aged ≥70 years had an incubation period 0·4 days [0·2 to 0·6] longer than participants aged 18-29 years), in female participants (by 0·1 days, 0·0 to 0·2), and in those who wore a mask during contact with the index case (by 0·2 days, 0·1 to 0·4), and was reduced in those for whom the index case was symptomatic (-0·1 days, -0·2 to -0·1). These data were robust to sensitivity analyses correcting for an over-reporting of incubation periods of 7 days. INTERPRETATION: SARS-CoV-2 incubation period is notably reduced in omicron cases compared with all other variants of concern, in young people, after transmission from a symptomatic index case, after transmission to a maskless secondary case, and (to a lesser extent) in men. These findings can inform future COVID-19 contact-tracing strategies and modelling. FUNDING: Institut Pasteur, the French National Agency for AIDS Research-Emerging Infectious Diseases, Fondation de France, the INCEPTION project, and the Integrative Biology of Emerging Infectious Diseases project.

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination. FINDINGS: We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71). INTERPRETATION: In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.

Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. FINDINGS: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. INTERPRETATION: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance "Tous unis contre le virus").

Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study.

BACKGROUND: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. FINDINGS: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). INTERPRETATION: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance" Tous unis contre le virus").

A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations.

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.

Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells.

Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world's population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.