Long-term health in individuals born preterm or with low birth weight: A cohort study.

BACKGROUND: To measure the association of prematurity and non-preterm low birth weight (LBW) with several long-term health outcomes. METHODS: We selected adult participants from the Constances cohort. Associations between preterm birth (<37 weeks versus ≥37 weeks) and outcomes were measured using modified Poisson regression with adjustment for participant age and parental history. We used the same modeling methods to measure the association between LBW (i.e.,

Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Relationship between night work and health-related quality of life: an analysis based on profiles and cumulative duration of exposure to night work among French workers in the CONSTANCES cohort.

OBJECTIVE: The aim of this study is to estimate the association between night work and health-related quality of life (HRQoL) among French workers. The association between cumulative duration of night work and HRQoL was also investigated. METHODS: Three career-long night work exposure groups were defined at inclusion in the CONSTANCES cohort: permanent night workers, rotating night workers and former night workers. Day workers with no experience of night work were the reference group. HRQoL was assessed using the Short Form Health Survey (SF-12), in particular the physical component summary (PCS) and mental component summary (MCS) scores, with a higher score indicating better HRQoL. Several linear regression models were built to test the association between night work exposure and HRQoL. The relationship between cumulative duration of night work and HRQoL scores was analyzed using generalised additive models. RESULTS: The sample consisted of 10,372 participants. Former night workers had a significantly lower PCS score than day workers (ß [95% CI]: - 1.09 [- 1.73; - 0.45], p = 0.001), whereas permanent night workers had a significantly higher MCS score (ß [95% CI]: 1.19 [0.009; 2.36], p = 0.048). A significant decrease in PCS score from 5 to 20 years of cumulative night work was observed among former night workers. CONCLUSIONS: Former night workers had poorer physical HRQoL in contrast to permanent and rotating night workers who had similar or even better HRQoL than day workers, suggesting the well-known healthy worker survivor effect. Consequently, both current and former night workers require regular and specific follow-up focused on the physical components of their health.

Impact of breast cancer care pathways and related symptoms on the return-to-work process: results from a population-based French cohort study (CONSTANCES).

BACKGROUND: Breast cancer (BC) treatments and related symptoms may affect return to work (RTW). The objective of this study was to investigate the impact of BC care pathways (timing and sequence of treatments) and related symptoms on RTW. METHODS: The study population included working-age women with BC who were enrolled in the French CONSTANCES cohort from 2012 to 2018. BC treatments, antidepressant/anxiolytic and antalgic drug deliveries (used as proxies of depression and pain, respectively) and statutory sick pay (used to estimate RTW and time to RTW) were assessed monthly using data from the French national healthcare system database. BC care pathways were identified with the sequence analysis method. Cox models with time-dependent covariates were used to investigate the impact of BC care pathways and related symptoms on RTW and time to RTW, after adjusting for age and socioeconomic characteristics. RESULTS: 73.2% (231/303) of women returned to work within 2 years after BC diagnosis. Five BC care pathway patterns were identified: (i) BC surgery only, (ii) BC surgery and radiotherapy, (iii) BC surgery and chemotherapy, (iv) BC surgery and chemotherapy and radiotherapy, and (v) BC surgery and long-term alternative chemotherapy/radiotherapy. The hazards ratios of non-RTW were significantly higher for women who received BC surgery and long-term alternative chemotherapy/radiotherapy and for > 55-year-old women. Time to RTW was significantly longer in women who received chemotherapy (patterns iii to v) and in women with antidepressant/anxiolytic and antalgic drug deliveries. CONCLUSION: This study highlights the value of considering the dynamic, cumulative and temporal features of BC care pathways and related symptoms to facilitate the RTW of women with BC.

Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

BACKGROUND AND AIMS: The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but NAFLD has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects. APPROACH AND RESULTS: The study population consisted of participants from the French nationwide Constances cohort from 2012 to 2019. Participants with a history of chronic viral hepatitis or excessive alcohol consumption were excluded. Noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The relationship between BW and NAFLD was analyzed with a sex-stratified logistic regression model adjusted for sociodemographic parameters, lifestyle, and birth term, whereas liver fibrosis was analyzed with a sex-stratified linear regression model. In total, 55,034 individuals with reliable BW were included (43% men, mean age: 38 years). NAFLD (FLI ≥ 60) was present in 5530 individuals (10%). Multivariate logistic regression showed a significant U-shaped relationship between BW and NAFLD, with no significant interaction with sex. A significant and slightly decreasing association was found between BW and Forns Index (ß = -0.05; p = 0.04). Premature birth (OR, 1.23; 95% CI, 1.03-1.48 for birth between 33 and 37 weeks versus ≥ 37 weeks) was associated with NAFLD, with a significant direct effect of premature birth, and without an indirect effect of low BW in mediation analysis. Forns Index was not significantly higher in participants with preterm birth compared to full-term birth. CONCLUSIONS: This large prospective adult-based cohort confirms the relationship between BW and NAFLD occurrence.

Impact of asthma on working life: an analysis of the French CONSTANCES cohort.

OBJECTIVES: Asthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset. METHODS: Using cross-sectional data collected at inclusion in the French CONSTANCES cohort in 2013-2014, we studied the links between each career path indicator (number of job periods, total duration of employment, numbers of part-time jobs and work interruptions due to unemployment or health issues, employment status at inclusion) on the one hand, and current asthma and asthma symptom score in the last 12 months on the other hand, as reported by the participants. Multivariate analyses were performed separately for men and women using logistic and negative binomial regression models adjusted for age, smoking status, body mass index and educational level. RESULTS: When the asthma symptom score was used, significant associations were observed with all of the career path indicators studied: a high symptom score was associated with a shorter total duration of employment as well as a greater number of job periods, part-time jobs and work interruptions due to unemployment or health issues. These associations were of similar magnitude in men and women. When current asthma was used, the associations were more pronounced in women for some career path indicators. CONCLUSION: The career path of asthmatic adults is more often unfavourable than that of those without asthma. Efforts should be made to support people with asthma in the workplace, in order to maintain employment and facilitate the return to work.

Household use of green and homemade cleaning products, wipe application mode, and asthma among French adults from the CONSTANCES cohort.

While exposure to irritant and sprayed cleaning products at home is known to have a harmful role in asthma, the potential health effect of other categories or forms has not been investigated. We studied the associations of household use of cleaning products, including green, homemade products, and disinfecting wipes, with asthma based on data from the large French population-based CONSTANCES cohort. Participants completed standardized questionnaires on respiratory health and household use of cleaning products. Cross-sectional associations of cleaning products with current asthma, adjusted for gender, age, smoking status, BMI, and educational level, were evaluated by logistic regressions. Analyses were conducted in 41 570 participants (mean age: 47 years, 56% women, weekly use of the six specific products/forms studied varied from 11% to 37%). Weekly use of irritants (OR = 1.23 [1.13-1.35]), scented (OR = 1.15 [1.06-1.26]), green (OR = 1.09 [1.00-1.20]), and homemade products (OR = 1.19 [1.06-1.34]), as well as sprays (OR = 1.18 [1.08-1.29]), disinfecting wipes (OR = 1.21 [1.09-1.34]) were significantly associated with asthma, with significant trends according to the frequency of use. When they were not co-used with irritants/sprays, associations were reduced and persisted only for disinfecting wipes. Weekly use of disinfecting wipes at home was associated with current asthma, but fewer risks were observed for the use of green and homemade products.

Underdiagnosis of obstructive lung disease: findings from the French CONSTANCES cohort.

BACKGROUND: The burden of undiagnosed obstructive lung disease (OLD) (mainly asthma and chronic obstructive pulmonary disease) is not fully established, and targets for corrective action are yet to be identified. We assessed the underdiagnosis of OLD and its determinants in France. METHODS: CONSTANCES is a French population-based cohort of adults aged 18-69 years at inception. We analysed data collected at inclusion in 2013-2014. Undiagnosed OLD was defined as spirometry-confirmed airflow limitation (FEV1/FVC < lower limit of normal) without prior diagnosis of asthma, chronic obstructive pulmonary disease, or bronchiectasis. Multivariate analysis was performed with weighted robust Poisson regression models to estimate the adjusted prevalence ratios (aPR) of undiagnosed OLD. RESULTS: Spirometry results were available for 19,398 participants. The prevalence of airflow limitation was 4.6%. Overall, 64.4% of adults with airflow limitation did not report a previous diagnosis of OLD. Individuals with high cumulative tobacco consumption (≥ 10 pack-years) (aPR: 1.72 [1.28-2.32]), without respiratory symptoms (aPR: 1.51 [1.28-1.78]), and with preserved lung function (aPR: 1.21 [1.04-1.41] for a 10-point increase in FEV1% predicted) had a higher risk of being undiagnosed. Half of symptomatic individuals with airflow limitation (45% of those with moderate to severe airflow limitation) were undiagnosed with OLD. CONCLUSION: Underdiagnosis of OLD is very common among French adults, even in patients with respiratory symptoms. Efforts should be made in France to raise awareness about OLD in the general population, improve the detection of respiratory symptoms, and increase the use of spirometry among primary care professionals.

Norms for Usual and Fast Walking Speed in Adults 45-69 Years Old From the French General Population: Constances Study.

OBJECTIVES: Walking speed (WS) represents an objective measure of motor function and health. We aimed to develop usual (UWS) and fast WS (FWS) norms for the general population using a regression-based approach, while considering age, sex, height, and education. DESIGN: Cross-sectional analysis of a population-based study. SETTING AND PARTICIPANTS: French Constances study (45-69 years). METHODS: UWS/FWS were measured over 3 m (dynamic start) using photoelectric cells. We addressed selection effects (related to survey sampling and nonresponse) and missing data using a combination of inverse probability weighting (IPW) and multiple imputation (MI). Norms by sex, age, height, and education (

Electronic cigarette use and respiratory symptoms in the French population-based Constances cohort.

BACKGROUND: Knowledge about the consequences of electronic cigarette (EC) use on respiratory health is still limited. We aimed to assess whether EC use is associated with the occurrence of asthma symptoms and chronic bronchitis among the French adult population, with a specific focus on never combustible cigarettes (CC) smokers. We further investigated whether the association differed in men and women. METHODS: Constances is a population-based cohort of adults aged 18-69 years at inception. We analyzed baseline data collected in 136,276 participants recruited in 2015-2019. Associations of current and former EC use with respiratory symptoms (asthma symptom score and chronic bronchitis) were assessed, controlling for CC smoking, cannabis use, demographics, education and body mass index (BMI). RESULTS: Increased frequencies of respiratory symptoms were observed in both current and former EC users (for the asthma symptom score, adjusted mean score ratio (aMSR): 1.34 [95 % confidence interval: 1.28-1.41] and 1.39 [1.33-1.45], respectively; for chronic bronchitis, adjusted prevalence ratio (aPR): 1.27 [1.19-1.36] and 1.40 [1.32-1.48], respectively). Among never CC smokers, ever EC use was associated with an increased asthma symptom score in both men and women (aMSR = 1.44 [1.09-1.90] and 1.36 [1.01-1.83], respectively), and with a higher prevalence of chronic bronchitis only in women (aPR = 1.97 [1.27-3.05]). CONCLUSION: EC use is associated with symptoms of asthma and chronic bronchitis, independently of CC smoking and cannabis use. The fact that these associations are observed among individuals who have never smoked tobacco adds further evidence of the deleterious effects of EC on respiratory health.

Development of a crosswalk to convert French PCS2003 into international ISCO88 occupational classifications. Application to the Occupational Asthma-specific Job-Exposure Matrix (OAsJEM).

INTRODUCTION: The problem of transcoding is recurrent when researchers wish to link occupational data from cohorts to Job-Exposure Matrices (JEMs) which were not set up in the same classifications. The Occupational Asthma-specific JEM (OAsJEM) is a JEM developed for assessing exposure to agents known at risk for asthma for jobs coded with ISCO88 occupation classification. To apply the OAsJEM in the CONSTANCES cohort, in which jobs and industries were coded with French PCS2003 and NAF2008 classifications respectively, we developed a crosswalk to convert jobs from PCS2003 into ISCO88 classification. METHODS: This work was carried out by 2 skilled coders and 1 novice coder who have worked independently by using different tools and transcoding strategies defined a priori. Consensus meetings were organized with skilled coders to define the final crosswalk. This work was elaborated in 2 steps: (i) for 38 ISCO88 codes classified as potentially exposed to cleaning and disinfection products by the OAsJEM, and (ii) for all jobs from the ISCO88 classification. A comparison between the 3 initial coder's crosswalk proposals and the final crosswalk was made for the 38 ISCO codes in step (i). RESULTS: The final crosswalk provided 998 matches between the 482 4-digit PCS2003 codes, 308 4-digit ISCO88 codes, and 31 3-digit ISCO88 codes. Information regarding the NAF2008 industry classification was also used in some cases to improve the final crosswalk. For the selected 38 ISCO88 codes, the final crosswalk provided 110 combinations, but the number of proposed ISCO88-PCS2003 couples by each of the 3 coders varied greatly from 68 to 153. In addition, an important variability between the 3 coders were observed among the number of common combinations between the initial coder's proposals and the final crosswalk (from 47% to 78%). DISCUSSION: We have developed a crosswalk specifically for an application of the OAsJEM in population-based surveys using the PCS2003 occupation classification. The development of this crosswalk is of great interest for the use of OAsJEM on the data of the CONSTANCES cohort and on any other survey with occupational data coded according to the French classifications. This OAsJEM crosswalk could be used by other teams to evaluate occupational exposures known to be at risk of asthma from occupational calendars coded with French classifications.

Asthma is associated with increased severity and duration of rhinitis: A study with the Allergic Rhinitis and its Impact on Asthma classes in the Constances cohort.

BACKGROUND: Few population-based studies have described allergic rhinitis (AR) according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification, and none have assessed the impact of asthma on this classification. Our aims were to 1) describe AR according to four ARIA classes and 2) within each of the four ARIA classes, compare participants with AR alone versus those with AR and asthma. METHODS: Cross-sectional analyses were performed using data from the 2014 annual follow-up questionnaire of the French adult population-based cohort Constances. Current AR was defined by the report of sneezing, runny, or blocked nose in the last 12 months and the report of nasal allergies. Following ARIA recommendations, rhinitis was classified according to its severity (mild or moderate-severe) and duration (intermittent or persistent). Ever asthma was also defined by a questionnaire. RESULTS: Among the 4675 participants with AR (57% women, mean age 50.2 ± 12.7 years), 44% were classified as mild/intermittent, 16% mild/persistent, 25% moderate-severe/intermittent, and 15% moderate-severe/persistent. Within each of the four ARIA classes, compared to participants with rhinitis alone, participants with rhinitis and asthma had significantly more severe symptoms, more conjunctivitis, a higher mean eosinophil count and more treatments with intra-nasal corticosteroids and oral antihistamines co-medication. CONCLUSIONS: This is a paradigm shift study as for the first time this large population-based study in adults showed that asthma status has a profound effect on the ARIA classification. Rhinitis alone and rhinitis with asthma represent two distinct phenotypes. These results reinforce the need to include asthma status in the ARIA classification and guidelines.

Cardiovascular burden and unemployment: A retrospective study in a large population-based French cohort.

The specific effect of unemployment on cardiovascular health relatively to the effects of social position and work environment is still unclear. To clarify this effect, the associations between current or past unemployment and the prevalence of common cardiovascular risk factor and events were tested using multiple logistic regression models with adjustment for both social position and prior work environment. The analyses were performed in a population-based French cohort (CONSTANCES) that included 131,186 adults enrolled between 2012 and 2021. Participants who were unemployed at inclusion (n = 8278) were overexposed to non-moderate alcohol consumption, smoking, leisure-time physical inactivity and depression (odds ratios (ORs) from 1.19 to 1.58) whereas those who have been unemployed at least once in the past (n = 19,015) were additionally overexposed not only to the previous risk factors but also to obesity, diabetes and sleep disorders (ORs from 1.10 to 1.35). These latter were also more exposed to non-fatal myocardial infarction and peripheral arterial disease (ORs of 1.44 and 1.47 respectively), overexposures that persisted after further adjustment for cardiovascular risk factors (ORs of 1.36 and 1.33). The overexposures to risk factors and cardiovascular events were both dependent on the duration of past unemployment. They were equally observed in participants with low social position or bad work environment. These results suggest that unemployment increases cardiovascular risk independently from social position and work environment with a cumulative effect over time. The effect of unemployment could add up to those of low social position and bad work environment during lifetime to further increase cardiovascular risk. They also suggest that long-term unemployment increases the prevalence of cardiovascular events through pathways including but not limited to overexposure to common risk factors.

Distinct cardiovascular and cancer burdens associated with social position, work environment and unemployment: a cross-sectional and retrospective study in a large population-based French cohort.

OBJECTIVES: Distinguish the respective effects of social position, work environment and unemployment on cardiovascular and cancer risks. DESIGN: A cross-sectional and retrospective observational study. SETTING: A population-based French cohort (CONSTANCES). PARTICIPANTS: 130 197 adults enrolled between 2012 and 2021 without missing values. PRIMARY OUTCOME MEASURES: The associations of social position, work environment and unemployment exposure with the prevalence of cardiovascular events and cancers simultaneously tested using logistic regression models adjusting for common risk factors. RESULTS: While social position, work environment and unemployment exposure are strongly inter-related with each other, they are not linked to the same cardiovascular and cancer outcomes. Low social position and long unemployment duration are significantly associated with an increased prevalence of angina pectoris, myocardial infarction and peripheral arterial disease (OR=1.22 to 1.90, p<0.04 to p<0.0001) but not of stroke. In contrast, a bad work environment is associated with an increased prevalence of stroke (OR=1.29, p<0.01) but not of angina pectoris, myocardial infarction and peripheral arterial disease. Low social position is associated with an increased prevalence of cervical and lung cancers (OR=1.73 and 1.95, p<0.002 and p<0.03) and a decreased prevalence of skin cancer (OR=0.70, p<0.0001) while a bad work environment is associated with an increased prevalence of breast, skin, prostate and colon cancers (OR=1.31 to 2.91, p<0.0002 to p<0.0001). Unemployment exposure is not associated with the prevalence of any type of cancers. CONCLUSIONS: Social position, work environment and unemployment are associated with distinct cardiovascular and cancerous diseases that could add up during lifetime, they should therefore be considered all together in any preventive strategy.

Early origins of metabolic and overall health in young adults: An outcome-wide analysis in a general cohort population.

INTRODUCTION: Long-term consequences of impaired fetal growth are well documented for cardiometabolic outcomes. We propose an outcome-wide analysis of the association between birth weight (BW) and long-term health in a large contemporary adult cohort. METHODS: The study included 73,315 participants under 60 years with a reliable BW from the French nationwide Constances cohort. Low and high BW (LBW/HBW) were defined as BW<10th and >90th of sex-specific percentiles. Associations between BW and outcomes were analyzed with a sex-stratified modified Poisson regression adjusted for the participant's age, maternal health history, geographical origins, and parents' occupation. RESULTS: Mean BW (10th -90th percentile) was 3390 g (2800-4000) for men and 3247g (2680-3820) for women. In men, LBW was associated with (RR [CI95]): fasting glucose impairment (1.33 [1.16;1.52]); hypertriglyceridemia (1.27 [1.17;1.37]); high blood pressure (HBP) (1.15 [1.07;1.24]); non-alcoholic fatty liver disease NAFLD (1.13 [1.02;1.24]); high LDL-cholesterol (1.12 [1.05;1.21]); anxiety (1.12 [1.01;1.24]) and depression (1.09 [1.00;1.18]). HBW was associated with obesity (1.21 [1.08;1.35]). In women, LBW was associated with fasting glucose impairment (1.31 [1.12;1.54]); HBP (1.27 [1.16;1.4]); hypertriglyceridemia (1.20 [1.05;1.36]); anxiety (1.10 [1.03;1.17]); and asthma (1.09 [1;1.19}). HBW was associated with obesity (1.24 [1.13;1.36]) and NAFLD (1.20 [1.06;1.37). LBW and HBW were associated with a lesser likelihood of tertiary education attainment in both sexes. Participants' education level was a significant partial mediator of the association between LBW and outcomes. CONCLUSION: Extreme BW is associated with long-term health. It should be considered in the personalized prevention of cardiometabolic, respiratory, and mental health conditions in adulthood, especially in socio-economically disadvantaged populations.

[Epidemiological studies based on medical and administrative databases : a potential strength in France]. / Cohortes épidémiologiques et bases de données d'origine administrative: un rapprochement potentiellement fructueux.

Population-based epidemiological cohorts may include nowadays hundreds of thousands of subjects, followed-up during decades. France has a major potential strength: nationwide medical and social databases set up for administrative purposes. The main databases useful for epidemiology are the social security database which contains individual medical data from different sources, and the retirement fund database on employment and social benefits. These databases have several advantages: they cover the whole French population, with no lost to follow-up, data are often of good quality and it is possible to link them with individual surveys. However medical data are not always ascertained and an important methodological and practical work has to be done, and some legal and practical problems have to be solved for an optimal use.

Respective Mediating Effects of Social Position and Work Environment on the Incidence of Common Cardiovascular Risk Factors.

Background Social position and work environment are highly interrelated and their respective contribution to cardiovascular risk is still debated. Methods and Results In a cohort of 20 625 French workers followed for 25 years, discrete-time survival analysis with reciprocal mediating effects, adjusted for sex, age, and parental history of early coronary heart disease, was performed using Bayesian structural equation modeling to simultaneously investigate the extent to which social position mediates the effect of work environment and, inversely, the extent to which work environment mediates the effect of social position on the incidence of common cardiovascular risk factors. Depending on the factor, social position mediates 2% to 53% of the effect of work environment and work environment mediates 9% to 87% of the effect of social position. The mediation by work environment is larger than that by social position for the incidence of obesity, hypertension, dyslipidemia, diabetes, sleep complaints, and depression (mediation ratios 1.32-41.5, 6.67 when modeling the 6 factors together). In contrast, the mediation by social position is larger than that by work environment for the incidence of nonmoderate alcohol consumption, smoking, and leisure-time physical inactivity (mediation ratios 0.16-0.69, 0.26 when modeling the 3 factors together). Conclusions The incidence of behavioral risk factors seems strongly dependent on social position whereas that of clinical risk factors seems closely related to work environment, suggesting that preventive strategies should be based on education and general practice for the former and on work organization and occupational medicine for the latter.

Persistent symptoms after the first wave of COVID-19 in relation to SARS-CoV-2 serology and experience of acute symptoms: A nested survey in a population-based cohort.

Background: Many patients report persistent symptoms after COVID-19. Our aim was to determine whether some of these symptoms were more associated with past SARS-CoV-2 infection compared to other conditions. Methods: This prospective survey was nested in CONSTANCES, a randomly selected French population-based cohort, started in 2012. All participants being followed-up by internet completed 2 questionnaires during the first wave of the pandemic focusing on the acute symptoms of their COVID-19-like illness. Serological tests for SARS-CoV-2 were then performed (May-Nov 2020). Between December 2020 and January 2021, participants completed a third questionnaire about symptoms that had lasted more than 2 months. Participants were classified into four groups according to both European Center for Diseases Control (ECDC) criteria for COVID-19 (ECDC+ or ECDC-) and serological SARS-CoV-2 test results (Sero+ or Sero-). To compare the risk of each persistent symptom among the groups, logistic regression models were adjusted for age, sex, educational level, comorbidities, and the number of acute symptoms declared during the first wave of the epidemic. A mediation analysis was performed to estimate the direct effect of the infection on persistent symptoms and its indirect effect via the initial clinical presentation. Findings: The analysis was performed in 25,910 participants. There was a higher risk of persistent dysgeusia/anosmia, dyspnea and asthenia in the ECDC+/Sero+ group than in the ECDC+/Sero- group (OR: 6.83 [4.47-10.42], 1.69 [1.07-2.6] and 1.48 [1.05-2.07], respectively). Abdominal pain, sensory symptoms or sleep disorders were at lower risk in the ECDC+/Sero+ group than in the ECDC+/Sero- group (0.51 [0.24-0.96], 0.40 [0.16-0.85], and 0.69 [0.49-0.95], respectively). The mediation analysis revealed that the association of the serological test results with each symptom was mainly mediated by ECDC symptoms (proportion mediated range 50-107%). Conclusion: A greater risk of persistent dysgeusia/anosmia, dyspnea and asthenia was observed in SARS-CoV-2 infected people. The initial clinical presentation substantially drives the association of positive serological test results with persistent symptoms. Funding: French National Research Agency.