Estimating SARS-CoV-2 infection probabilities with serological data and a Bayesian mixture model.

The individual results of SARS-CoV-2 serological tests measured after the first pandemic wave of 2020 cannot be directly interpreted as a probability of having been infected. Plus, these results are usually returned as a binary or ternary variable, relying on predefined cut-offs. We propose a Bayesian mixture model to estimate individual infection probabilities, based on 81,797 continuous anti-spike IgG tests from Euroimmun collected in France after the first wave. This approach used serological results as a continuous variable, and was therefore not based on diagnostic cut-offs. Cumulative incidence, which is necessary to compute infection probabilities, was estimated according to age and administrative region. In France, we found that a "negative" or a "positive" test, as classified by the manufacturer, could correspond to a probability of infection as high as 61.8% or as low as 67.7%, respectively. "Indeterminate" tests encompassed probabilities of infection ranging from 10.8 to 96.6%. Our model estimated tailored individual probabilities of SARS-CoV-2 infection based on age, region, and serological result. It can be applied in other contexts, if estimates of cumulative incidence are available.

Impact of Translation on Biomedical Information Extraction: Experiment on Real-Life Clinical Notes.

Background: Biomedical natural language processing tasks are best performed with English models, and translation tools have undergone major improvements. On the other hand, building annotated biomedical data sets remains a challenge. Objective: The aim of our study is to determine whether the use of English tools to extract and normalize French medical concepts based on translations provides comparable performance to that of French models trained on a set of annotated French clinical notes. Methods: We compared 2 methods: 1 involving French-language models and 1 involving English-language models. For the native French method, the named entity recognition and normalization steps were performed separately. For the translated English method, after the first translation step, we compared a 2-step method and a terminology-oriented method that performs extraction and normalization at the same time. We used French, English, and bilingual annotated data sets to evaluate all stages (named entity recognition, normalization, and translation) of our algorithms. Results: The native French method outperformed the translated English method, with an overall F1-score of 0.51 (95% CI 0.47-0.55), compared with 0.39 (95% CI 0.34-0.44) and 0.38 (95% CI 0.36-0.40) for the 2 English methods tested. Conclusions: Despite recent improvements in translation models, there is a significant difference in performance between the 2 approaches in favor of the native French method, which is more effective on French medical texts, even with few annotated documents.

Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study.

BACKGROUND: Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions. OBJECTIVE: This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6-10 months later. METHODS: A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome. FINDINGS: At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up. CONCLUSIONS: The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline. CLINICAL IMPLICATIONS: Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

SARS-CoV-2 infection prevalence and associated factors among primary healthcare workers in France after the third COVID-19 wave.

Data on the SARS-CoV-2 infection among primary health care workers (PHCWs) are scarce but essential to reflect on policy regarding prevention and control measures. We assessed the prevalence of PHCWs who have been infected by SARS-CoV-2 in comparison with modeling from the general population in metropolitan France, and associated factors. A cross-sectional study was conducted among general practitioners (GPs), pediatricians, dental and pharmacy workers in primary care between May and August 2021. Participants volunteered to provide a dried-blood spot for SARS-CoV-2 antibody assessment and completed a questionnaire. The primary outcome was defined as the detection of infection-induced antibodies (anti-nucleocapsid IgG, and for non-vaccinees: anti-Spike IgG and neutralizing antibodies) or previous self-reported infection (positive RT-qPCR or antigenic test, or positive ELISA test before vaccination). Estimates were adjusted using weights for representativeness and compared with prediction from the general population. Poisson regressions were used to quantify associated factors. The analysis included 1612 PHCWs. Weighted prevalences were: 31.7% (95% CI 27.5-36.0) for GPs, 28.7% (95% CI 24.4-33.0) for pediatricians, 25.2% (95% CI 20.6-31.0) for dentists, and 25.5% (95% CI 18.2-34.0) for pharmacists. Estimates were compatible with model predictions for the general population. PHCWs more likely to be infected were: GPs compared to pharmacist assistants (adjusted prevalence ratio [aPR] = 2.26; CI 95% 1.01-5.07), those living in Île-de-France (aPR = 1.53; CI 95% 1.14-2.05), South-East (aPR = 1.57; CI 95% 1.19-2.08), North-East (aPR = 1.81; CI 95% 1.38-2.37), and those having an unprotected contact with a COVID-19 case within the household (aPR = 1.48; CI 95% 1.22-1.80). Occupational factors were not associated with infection. In conclusion, the risk of SARS-CoV-2 exposure for PHCWs was more likely to have occurred in the community rather than at their workplace.

Impact of translation on biomedical information extraction: an experiment on real-life clinical notes.

BACKGROUND: Biomedical natural language processing tasks are best performed with English models, and translation tools have undergone major improvements. On the other hand, building annotated biomedical datasets remains a challenge. OBJECTIVE: The aim of our study is to determine whether the use of English tools to extract and normalize French medical concepts on translations provides comparable performance to that of French models trained on a set of annotated French clinical notes. METHODS: We compare two methods: one involving French-language models and one involving English-language models. For the native French method, the Named Entity Recognition (NER) and normalization steps are performed separately. For the translated English method, after the first translation step, we compare a two-step method and a terminology-oriented method that performs extraction and normalization at the same time. We used French, English and bilingual annotated datasets to evaluate all stages (NER, normalization and translation) of our algorithms. RESULTS: The native French method outperformed the translated English method, with an overall f1 score of 0.51 [0.47;0.55], compared with 0.39 [0.34;0.44] and 0.38 [0.36;0.40] for the two English methods tested. CONCLUSIONS: Despite recent improvements in translation models, there is a significant difference in performance between the two approaches in favor of the native French method, which is more effective on French medical texts, even with few annotated documents.

Real-world economic burden of hepatitis C and impact of direct-acting antivirals in France: A nationwide claims data analysis.

BACKGROUND AND AIMS: The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data. METHODS: Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS. RESULTS: A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy. CONCLUSIONS: A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.

Hepatitis C virus cure from direct-acting antivirals and mortality: Are people with and without a history of injection drug use in the same boat? (ANRS CO22 Hepather cohort).

INTRODUCTION: The risk of mortality in people with a history of injection drug use (PHID) is high, as is the prevalence of hepatitis C virus (HCV) infection. Although direct-acting antivirals (DAA) are effective in this population in terms of sustained virological response, it is not known whether PHID benefit as much as people with no history of injection drug use from DAA-related HCV cure in terms of reduced all-cause mortality. METHODS: Using Cox proportional hazards models based on the ANRS CO22 Hepather cohort data (n = 9735), we identified factors associated with all-cause mortality among HCV-infected people. We tested for interaction effects between drug injection status, HCV cure and other explanatory variables. RESULTS: DAA-related HCV cure was associated with a 66% (adjusted hazard ratio [95% confidence interval]: 0.34 [0.29-0.39]) lower risk of all-cause mortality, irrespective of drug injection status. Detrimental effects of unhealthy alcohol use on mortality were identified in PHID only. DISCUSSION AND CONCLUSIONS: DAA-related HCV cure led to comparable benefits in terms of reduced mortality in PHID and people with no history of injection drug use. Policies and strategies to enhance DAA uptake among PHID are needed to lower mortality in this population. Clinical trial registration details: ClinicalTrials.gov: NCT01953458.

Heart and systemic sclerosis-findings from a national cohort study.

OBJECTIVES: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc. METHODS: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors. RESULTS: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence. CONCLUSIONS: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes.

SARS-CoV-2 seroprevalence in French 9-year-old children and their parents after the first lockdown in 2020.

Introduction: Children have been significantly less affected by COVID-19 than adults and presented with milder and less symptomatic forms of the disease. However, there has been suggestion that children older than 10 years and adolescents exhibits features closer to that of young adults. Most studies combine children in different age-groups and lack sufficient numbers to explore in detail age specificities. We report data on a population-based sample of 2,555 children at the pivotal age of 9 years. Methods: In April 2020, the participants in two French nationwide cohorts of children, Elfe and Epipage2, were invited to take part into an online survey about Covid related symptoms and family life during the lockdown. A second questionnaire was sent on May 5. This questionnaire also proposed to the child included in the cohort and to one of his/her parents to take part into a capillary blood collection for Covid serology. Families who agreed to the serological survey were sent kits for dried blood spots self-sampling (DBS) with instructions. Samples were processed with a commercial Elisa test (Euroimmun®, Lübeck, Germany) to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus. Results: Children's acceptance rate for the serological survey was around 60%. 2,555 serological results were analyzed. The weighted prevalence of a positive Elisa Spike serology was 2.8% in 9 yr-old children (95% CI: 1.7%-4.0%). Positive serology was found in 8.6% (7.4%-9.7%) of parents who provided blood. There was a significant association (p < 0.001) between serology of the child and parent from the same household with an odds ratio of 13.8 (7.9-24.2). Discussion: We have shown that 9-yr old children had a lower susceptibility to SARS-Cov2 infection than adults with the initial Chinese strain, similar to younger children and estimated that around 3% of them have developed antibodies against SARS-Cov2 in France after the first wave of the Covid-19 epidemics.

Spike protein genetic evolution in patients at high-risk of severe COVID-19 treated by monoclonal antibodies.

BACKGROUND: High-risk patients, often immunocompromised and not responding to vaccine, continue to experience severe COVID-19 and death. Monoclonal antibodies (mAbs) were shown effective to prevent severe COVID-19 for these patients. Nevertheless, concerns about the emergence of resistance mutations were raised. METHODS: We conducted a multicentric prospective cohort study, including 264 patients with mild-to moderate COVID-19 at high risk for progression to severe COVID-19 and treated early with Casirivimab/Imdevimab, Sotrovimab or Tixagevimab/Cilgavimab. We sequenced the SARS-CoV-2 genome during follow-up and searched for emerging Spike mutations. RESULTS: Immunocompromised patients have a 6-fold increased risk of developing mutations, which are associated with a prolonged duration of viral clearance but no clinical worsening. Emerging P337S/R/L/H, E340D/K/A/Q/V/G and K356T/R substitutions in patients treated with Sotrovimab are associated with higher viral RNA loads for up to 14 days post-treatment initiation. Tixagevimab/Cilgavimab is associated with a 5-fold increased risk of developing mutations. R346K/I/T/S and K444R/N/M substitutions associated with Tixagevimab/Cilgavimab have been identified in multiple SARS-CoV-2 lineages, including BQ.1 and XBB. CONCLUSIONS: In conclusion, the probability of emerging mutations arising in response to mAbs is significant, emphasizing the crucial need to investigate these mutations thoroughly and assess their impact on patients and the evolutionary trajectory of the SARS-CoV-2.

Association of SARS-CoV-2 infection with physical activity domains and types.

Lockdown imposed in the early phase of the SARS-CoV-2 outbreak represented a specific setting where activity was restricted but still possible. The aim was to investigate the cross-sectional associations between physical activity (PA) and SARS-CoV-2 infection in a French population-based cohort. Participants completed a PA questionnaire. PA was classified into: (i) total PA; (ii) aerobic PA by intensity; (iii) strengthening PA; (iv) PA by domain and type; and (vii) by location. Sedentary time was also recorded. Seroprevalence of anti-SARS-CoV-2 antibodies was assessed. Multivariable logistic regression models controlling for sociodemographic, lifestyle, anthropometric data, health status, and adherence to recommended protective anti-SARS-CoV-2 behaviours were computed. From 22,165 participants included, 21,074 (95.1%) and 1091 (4.9%) had a negative and positive ELISA-S test result, respectively. Total PA, vigorous PA, leisure-time PA, household PA, outdoor PA and indoor PA were all associated with lower probability of SARS-CoV-2 infection. Observations made in such a setting shed light on PA possibilities in a context of restricted mobility, where the health benefits of PA should not be overlooked. Along with already well-established benefits of PA for non-communicable disease prevention, these findings provide additional evidence for policies promoting all types of PA as a lever for population health.

Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients.

Antibodies effective against the recent Omicron sublineages are missing. By taking advantage of a multi-centric prospective cohort of immunocompromised individuals treated for mild-to-moderate COVID-19, Bruel et al. show that administration of 500 mg of sotrovimab induces serum neutralization and antibody-dependent cellular cytotoxicity of BQ.1.1 and XBB.1.5. Therefore, sotrovimab may remain a therapeutic option against these variants.

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.

Impaired health-related quality of life in the HCV cure era: who is concerned? (ANRS CO22 HEPATHER French cohort).

PURPOSE: Hepatitis C virus (HCV) cure after treatment with direct-acting antivirals (DAAs) can improve health-related quality of life (HRQoL). However, specific groups with chronic HCV may still exhibit worse post-cure HRQoL because of persisting severe liver fibrosis or social vulnerability factors (e.g. unhealthy alcohol use, living in poverty). We assessed the effect of such factors on longitudinal measures of HRQoL in chronic HCV patients. METHODS: ANRS CO22 HEPATHER is a prospective cohort of chronic HCV patients receiving DAAs, which included notably patients with social vulnerability factors, a population usually under-represented in clinical trials. Multivariable mixed-effects linear regression models helped identify factors associated with longitudinal measures of HRQoL (PROQOL-HCV scores). RESULTS: At enrolment, 52.4% of the 2740 participants were men, median age was 56 years [interquartile range 50-64], and 21.5% had severe liver fibrosis (FIB-4 > 3.25). Twenty-eight per cent reported current or past unhealthy alcohol use [> 2(3) alcohol units per day for women (men)], and 28.1% were living in poverty (standard of living under 1015€/month per household consumption unit). At first PROQOL-HCV completion, 54.0% of patients were HCV-cured. After multivariable adjustment, people with current or past unhealthy alcohol use, individuals living in poverty, those with severe liver fibrosis, and women had worse HRQoL in the dimensions explored. Conversely, HCV cure was associated with better HRQoL. CONCLUSIONS: Specific socially vulnerable groups of patients with chronic HCV infection still experience impaired HRQoL, independently of HCV cure. Patient-centred interventions, including social support and referral for comorbidities, should be prioritized for them. Trial registration with ClinicalTrials.gov NCT01953458.

Updating mortality risk estimation in intensive care units from high-dimensional electronic health records with incomplete data.

BACKGROUND: The risk of mortality in intensive care units (ICUs) is currently addressed by the implementation of scores using admission data. Their performances are satisfactory when complications occur early after admission; however, they may become irrelevant in the case of long hospital stays. In this study, we developed predictive models of short-term mortality in the ICU from longitudinal data. METHODS: Using data collected throughout patients' stays of at least 48 h from the MIMIC-III database, several statistical learning approaches were compared, including deep neural networks and penalized regression. Missing data were handled using complete-case analysis or multiple imputation. RESULTS: Complete-case analyses from 19 predictors showed good discrimination (AUC > 0.77 for several approaches) to predict death between 12 and 24 h onward, yet excluded 75% of patients from the initial target cohort, as data was missing for some of the predictors. Multiple imputation allowed us to include 70 predictors and keep 95% of patients, with similar performances. CONCLUSION: This proof-of-concept study supports that automated analysis of electronic health records can be of great interest throughout patients' stays as a surveillance tool. Although this framework relies on a large set of predictors, it is robust to data imputation and may be effective early after admission, when data are still scarce.

Antiviral activities of sotrovimab against BQ.1.1 and XBB.1.5 in sera of treated patients.

Background: Monoclonal antibodies (mAbs) targeting the spike of SARS-CoV-2 prevent severe COVID-19. Omicron subvariants BQ.1.1 and XBB.1.5 evade neutralization of therapeutic mAbs, leading to recommendations against their use. Yet, the antiviral activities of mAbs in treated patients remain ill-defined. Methods: We investigated neutralization and antibody-dependent cellular cytotoxicity (ADCC) of D614G, BQ.1.1 and XBB.1.5 in 320 sera from 80 immunocompromised patients with mild-to-moderate COVID-19 prospectively treated with mAbs (sotrovimab, n=29; imdevimab/casirivimab, n=34; cilgavimab/tixagevimab, n=4) or anti-protease (nirmatrelvir/ritonavir, n=13). We measured live-virus neutralization titers and quantified ADCC with a reporter assay. Findings: Only Sotrovimab elicits serum neutralization and ADCC against BQ.1.1 and XBB.1.5. As compared to D614G, sotrovimab neutralization titers of BQ.1.1 and XBB.1.5 are reduced (71- and 58-fold, respectively), but ADCC levels are only slightly decreased (1.4- and 1-fold, for BQ.1.1 and XBB.1.5, respectively). Interpretation: Our results show that sotrovimab is active against BQ.1.1 and XBB.1.5 in treated individuals, suggesting that it may be a valuable therapeutic option.

Direct-Acting Antivirals and the Risk of Arrhythmias and Conduction Disorders in Patients with Chronic Hepatitis C: A French Nationwide Cohort Study.

OBJECTIVE: To quantify the risk of arrhythmias and conduction disorders (ACD) in patients receiving direct-acting antiviral (DAA) therapy for hepatitis C. DESIGN: All individuals aged 18 to 85 years old treated with DAAs between 01 January 2014 and 31 December 2021 were selected from the French national healthcare database (SNDS). Individuals with a history of ACD were excluded. The primary outcome was the incidence of hospitalization or medical procedure for ACD. Marginal structural models were used to adjust for age, sex, medical comorbidities, and concomitant medications. RESULTS: After analyzing 87,589 individuals (median age, 52 years; 60% male) from 01 January 2014 to 31 December 2021, 2131 hospitalizations or medical procedures for ACD were observed over 672,572 person-years (PY) of follow-up. The incidence of ACD was 245/100,000 PY [95% confidence interval (CI), 228-263/100,000 PY] before DAA and 375/100,000 PY (95% CI 355-395/100,000 PY) after DAA exposure (rate ratio 1.53; 95% CI 1.40-1.68; P < 0.001). The risk of ACD was increased after DAA exposure, compared with the pre-DAA period (adjusted hazard ratio,1.66; 95% CI 1.43-1.93; P < 0.001). The increase in ACD risk was similar among individuals treated with sofosbuvir-based and sofosbuvir-free regimens. Of the 1398 ACD detected after DAA exposure, 30% were hospitalizations for atrial fibrillation, 25% were medical procedures for ACD, and 15% were hospitalizations for atrioventricular blocks. CONCLUSION: A significant increase in the risk of ACD was observed in the population-level cohort of individuals treated with DAAs, regardless of the regimen. Further research is needed to identify patients at risk of ACD, determine cardiac monitoring strategies, and evaluate the need for Holter monitoring after DAA therapy.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

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.