Immunogenicity and efficacy of          heterologous ChAdOx1-BNT162b2 vaccination.

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.

Combining SARS-CoV-2 interferon-gamma release assay with humoral response assessment to define immune memory profiles.

OBJECTIVES: In the post-SARS-CoV-2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti-Spike (S) immunoglobulin-G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T-cell response assessment to enhance the definition of immune memory profile. METHODS: SARS-CoV-2 interferon-gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti-receptor-binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. RESULTS: Close to 40% of our samples were exclusively IGRA-positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long-lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti-receptor-binding domain IgG and IGRA levels tended to reduce it. CONCLUSION: The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level.

Outcome of the Compensation Process Initiated by an Occupational and Environmental Diseases Center.

BACKGROUND: Regional Centers for Occupational and Environmental Pathologies (CRPPE) are responsible for identifying possible occupational etiologies of pathologies. When an occupational origin is determined, an Initial Medical Certificate (IMC) is given to the patient to allow him to initiate a procedure for recognition as an occupational disease (OD) by his health insurance organization. OBJECTIVES: The main aim of this study was to investigate the outcome of occupational disease claims in patients who received an IMC delivered by the CRPPE of Lyon. METHODS: A telephone interview was systematically conducted with patients who consulted the CRPPE for a claim for occupational disease recognition between 07/2020 and 06/2021, about six months after the consultation. It was conducted by a physician using a standardized questionnaire. RESULTS: Out of 128 patients eligible for this study, 98 were included. Diseases of the respiratory system (34.7%) and cancers (28.6%) were the most common pathologies in our population. A process of OD compensation was initiated by 86 patients (87.8%). At the time of the study, the outcome was favorable for 63 patients (73.3%). Moreover, 18 patients (18.4%) wished for additional help from the CRPPE to carry out the procedures. Nine patients requested a new consultation, including five who still needed to complete the process. CONCLUSION: This study shows the benefit of a consultation by occupational disease consultants. However, difficulties still need to be solved in these procedures. Thus, the systematic follow-up of patients shows its advantages. The provision of support to carry out the process seems necessary.

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022.

BackgroundTo cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections.

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.

Specific detection of memory T-cells in COVID-19 patients using standardized whole-blood Interferon gammarelease assay.

Antigen-specific T-cells are essential for protective immunity against SARS-CoV-2. We set up a semi-automated whole-blood Interferon-gamma release assay (WB IGRA) to monitor the T-cell response after stimulation with SARS-CoV-2 peptide pools. We report that the WB IGRA is complementary to serological assays to assess SARS-CoV-2 immunity.

Evaluation of Commercial Anti-SARS-CoV-2 Antibody Assays and Comparison of Standardized Titers in Vaccinated Health Care Workers.

With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus-2 antibodies (Ab) evolved toward quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after one dose (convalescent individuals) or two doses (naive individuals) of vaccine, in health care workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with five quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti-RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/mL correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assay to express the results in IU/mL.

Evaluation of High-Throughput SARS-CoV-2 Serological Assays in a Longitudinal Cohort of Patients with Mild COVID-19: Clinical Sensitivity, Specificity, and Association with Virus Neutralization Test.

BACKGROUND: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. METHODS: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. RESULTS: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3% (78.1-96.1), and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC < 0.76). CONCLUSIONS: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.

Interventions developed with the Intervention Mapping protocol in the field of cancer: A systematic review.

OBJECTIVES: The Intervention Mapping (IM) protocol provides a structured framework to develop, implement, and evaluate complex interventions. The main objective of this review was to identify and describe the content of the interventions developed in the field of cancer with the IM protocol. Secondary objectives were to assess their fidelity to the IM protocol and to review their theoretical frameworks. METHODS: Medline, Web of Science, PsycINFO, PASCAL, FRANCIS, and BDSP databases were searched. All titles and abstracts were reviewed. A standardized extraction form was developed. All included studies were reviewed by 2 reviewers blinded to each other. RESULTS: Sixteen studies were identified, and these reported 15 interventions. The objectives were to increase cancer screening participation (n = 7), early consultation (n = 1), and aftercare/quality of life among cancer survivors (n = 7). Six reported a complete participatory planning group, and 7 described a complete logic model of the problem. Ten studies described a complete logic model of change. The main theoretical frameworks used were the theory of planned behaviour (n = 8), the transtheoretical model (n = 6), the health belief model (n = 6), and the social cognitive theory (n = 6). The environment was rarely integrated in the interventions (n = 4). Five interventions were reported as effective. CONCLUSIONS: Culturally relevant interventions were developed with the IM protocol that were effective to increase cancer screening and reduce social disparities, particularly when they were developed through a participative approach and integrated the environment. Stakeholders' involvement and the role of the environment were heterogeneously integrated in the interventions.

Development of the Return-to-Work Obstacles and Self-Efficacy Scale (ROSES) and Validation with Workers Suffering from a Common Mental Disorder or Musculoskeletal Disorder.

Introduction Common mental disorders (CMDs) and musculoskeletal disorders (MSDs) lead the list of causes for work absence in several countries. Current research is starting to look at workers on sick leave as a single population, regardless of the nature of the disease or accident. The purpose of this study is to report the validation of the Return to Work Obstacles and Self-Efficacy Scale (ROSES) for people with MSDs and CMDs, based on the disability paradigm. Methods From a prospective design, the ROSES' reliability and validity were investigated in a Canadian sample of workers on sick leave due to MSDs (n = 206) and CMDs (n = 157). Results Exploratory and confirmatory factor analyses revealed that 46 items spread out on 10 conceptual dimensions (e.g., Fears of a relapse, Job demands, Difficult relation with the immediate supervisor), with satisfactory alpha coefficients and test-retest reliability for all subscales. Finally, several dimensions of ROSES also predict the participant's RTW within 6 months for MSDs (e.g., job demands), and CMDs (e.g., difficult relation with the immediate supervisor), even when adjusted by several variables (e.g., age, severity of symptoms). Apart from the job demands dimension, when the ROSES dimension is more external to the individual, only the perception of obstacles remains significant to predict RTW whereas it is the opposite result when the dimension is more internal (e.g., fears of a relapse). Conclusion The ROSES demonstrated satisfactory results regarding its validity and reliability with people having MSDs or CMDs, at the time of the return-to-work process.

Pre-employment examinations for preventing injury, disease and sick leave in workers.

BACKGROUND: Many employers and other stakeholders believe that health examinations of job applicants prevent occupational diseases and sickness absence. This is an update of the original Cochrane review (Mahmud 2010). OBJECTIVES: To evaluate the effectiveness of pre-employment examinations of job applicants in preventing occupational injury, disease and sick leave compared to no intervention or alternative interventions. SEARCH METHODS: We searched CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO and PEDro (up to 31 March 2015). We did not impose any restrictions on date, language or publication type. SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled before-after (CBA) studies, and interrupted time-series (ITS) studies of health examinations to prevent occupational diseases and injuries in job applicants in comparison to no intervention or alternative interventions. DATA COLLECTION AND ANALYSIS: All five review authors independently selected studies from the updated search for inclusion. We retrieved two new studies with the updated search from 1 April 2008 to 31 March 2015, resulting in a total of eleven studies. MAIN RESULTS: We included two RCTs, seven CBA studies and two ITS studies. Nine studies with 7820 participants evaluated the screening process of pre-employment examinations as a whole, and two studies with 2164 participants evaluated the measures to mitigate the risks found following the screening process. The studies were too heterogeneous for statistical pooling of results. We rated the quality of the evidence for all outcomes as very low quality. The two new CBA studies both used historical controls and both had a high risk of bias.Of those studies that evaluated the screening process, there is very low quality evidence based on one RCT that a general examination for light duty work may not reduce the risk for sick leave (mean difference (MD) -0.09, 95% confidence interval (CI) -0.47 to 0.29). For army recruits, there is very low quality evidence based on one CBA study that there is a positive effect on fitness for duty after 12 months follow-up (odds ratio (OR) 0.40, 95% CI 0.19 to 0.85).We found inconsistent evidence of an effect of job-focused pre-employment examinations on the risk of musculoskeletal injuries in comparison with general or no pre-employment examination based on one RCT with high risk of bias, and four CBA studies. There is very low quality evidence based on one ITS study that incorporation of a bronchial challenge test may decrease occupational asthma (trend change -2.6, 95% CI -3.6 to -1.5) compared to a general pre-employment examination with lung function tests.Pre-employment examinations may also result in a rejection of the applicant for the new job. In six studies, the rates of rejecting job applicants increased because of the studied examinations , on average, from 2% to 35%, but not in one study.There is very low quality evidence based on two CBA studies that risk mitigation among applicants considered not fit for work at the pre-employment examination may result in a similar risk of work-related musculoskeletal injury during follow-up compared to workers considered fit for work at the health examination. AUTHORS' CONCLUSIONS: There is very low quality evidence that a general examination for light duty work may not reduce the risk for sick leave, but may have a positive effect on fitness for duty for army recruits after 12 months follow-up.There is inconsistent evidence of an effect of job-focused pre-employment examinations on the risk of musculoskeletal injuries in comparison with general or no pre-employment examination. There is very low quality evidence that incorporation of a bronchial challenge test may decrease occupational asthma compared to a general pre-employment examination with lung function tests. Pre-employment examinations may result in an increase of rejecting job applicants in six out of seven studies. Risk mitigation based on the result of pre-employment examinations may be effective in reducing an increased risk for occupational injuries based on very low quality evidence. This evidence supports the current policy to restrict pre-employment examinations to only job-specific examinations. Better quality evaluation studies on pre-employment examinations are necessary, including the evaluation of the benefits of risk mitigation, given the effect on health and on the financial situation for those employees who do not pass the pre-employment examination.

Job Restrictions for Healthcare Workers with Musculoskeletal Disorders: Consequences from the Superior's Viewpoint.

Objective Many workers suffer from musculoskeletal disorders. In France, occupational physicians are able to set job aptitude restrictions obliging employers to adapt the worker's job. The present study explored the impact of job restriction from the point of view of the employees' supervisors. Methods A qualitative study was conducted in 3 public hospitals. 12 focus groups were organized, involving 61 charge nurses and head nurses supervising 1 or more workers restricted for heavy lifting or repetitive movements. Discussions were recorded for qualitative thematic analysis. Results Charge and head nurses complained that aptitude restrictions were insufficiently precise, could not be respected and failed to mention residual capability. A context of personnel cuts, absenteeism and productivity demands entailed a need for polyvalence and reorganization threatening the permanence of adapted jobs. Job restrictions had several negative consequences for the charge and head nurses, including overwork, increased conflict, and feelings of isolation and organizational injustice. Conclusion Protecting the individual interests of workers with health issues may infringe on the interests of their supervisors and colleagues, whose perception of organizational justice may go some way to explaining the support or rejection they show toward restricted workers. This paradox should be explicitly explored and discussed.

Using Cartoons to Transfer Knowledge Concerning the Principles of Work Disability Prevention Among Stakeholders.

Purpose This study assesses how well two cartoons transfer knowledge of principles of work disability prevention among stakeholders, according to their level of experience. We also document stakeholders' perceptions of the usefulness of the cartoons. Method We performed a descriptive study. Two groups of stakeholders were recruited: (1) experienced (working for more than 2 years in work disability), (2) non-experienced (in training). A self-administered questionnaire with open-ended questions documented stakeholders' understanding of each cartoon box and their perception of the possible usefulness of the cartoons. We transformed qualitative responses into quantitative responses for descriptive purposes. We performed independent t tests to compare the groups' level of understanding, and content analysis for the perception of usefulness. Results Overall, 149 stakeholders (50 experienced and 99 non-experienced) participated and identified 79.4 and 61.4 % of all principles presented in each of the two cartoons respectively. Experienced stakeholders identified more principles compared to non-experienced stakeholders (p = 0.007). Both cartoons were perceived to be useful for knowledge transfer. Conclusions Principles were generally well identified in the cartoons by all participants. Cartoons can be used as an effective tool among stakeholders to achieve a common understanding in order to coordinate their actions.

Impact of a program to prevent incivility towards and assault of healthcare staff in an ophtalmological emergency unit: study protocol for the PREVURGO On/Off trial.

BACKGROUND: The emergency department has been identified as an area within the health care sector with the highest reports of violence. The best way to control violence is to prevent it before it becomes an issue. Ideally, to prevent violent episodes we should eliminate all triggers of frustration and violence. Our study aims to assess the impact of a quality improvement multi-faceted program aiming at preventing incivility and violence against healthcare professionals working at the ophthalmological emergency department of a teaching hospital. METHODS/DESIGN: This study is a single-center prospective, controlled time-series study with an alternate-month design. The prevention program is based on the successive implementation of five complementary interventions: a) an organizational approach with a standardized triage algorithm and patient waiting number screen, b) an environmental approach with clear signage of the premises, c) an educational approach with informational videos for patients and accompanying persons in waiting rooms, d) a human approach with a mediator in waiting rooms and e) a security approach with surveillance cameras linked to the hospital security. The primary outcome is the rate of incivility or violence by patients, or those accompanying them against healthcare staff. All patients admitted to the ophthalmological emergency department, and those accompanying them, will be enrolled. In all, 45,260 patients will be included in over a 24-month period. The unit analysis will be the patient admitted to the emergency department. Data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and patients will not be blinded. DISCUSSION: The strengths of this study include the active solicitation of event reporting, that this is a prospective study and that the study enables assessment of each of the interventions that make up the program. The challenge lies in identifying effective interventions, adapting them to the context of care in an emergency department, and thoroughly assessing their efficacy with a high level of proof.The study has been registered as a cRCT at clinicaltrials.gov (identifier: NCT02015884).

Planning Individual and Population-Based Interventions in Global Health: Applying the DEA-A Framework to Promote Behavioral, Emotional, and/or Cognitive Change among Stakeholders.

Addressing health challenges that impact human well-being requires a comprehensive, interdisciplinary approach that would be at the crossroad of population-based prevention and individual-level clinical care, which is in line with a Global Health perspective. In the absence of a unifying theoretical framework to guide such interventions, a Dynamic Ecosystem Adaptation through the Allostasis (DEA-A) framework has been proposed, emphasizing the functional adaptation of individuals and organizations in symbiosis with their living ecosystem. While a conceptual model has been presented, this methodological contribution aims at illustrating the practical application of the DEA-A framework for planning Global Health interventions. The methodology combines Intervention Mapping and Cognitive and Behavioral Theory, extended to the ecosystem. Practical guidelines and supporting tools are provided to help public health providers and clinicians in establishing a functional ecosystem diagnosis of the issue; defining not only behavioral, but also emotional and cognitive change objectives (allostasis targets) expected for each stakeholder; and designing intervention plans targeting determinants of these allostasis. The discussion addresses implementation and evaluation perspectives of interventions based on the DEA-A framework, emphasizing the importance of considering change in its processual and ecosystem complexity. Lastly, encouragements for a deeper understanding of individual and ecosystem homeostasis/allostasis processes are made in order to promote more functional interventions.

Implementing Indicators and Trajectories of Return to Work After Breast Cancer Diagnosis: A Mixed-Methods Study Using the French National Healthcare Insurance Database and Stakeholder Consultation.

PURPOSE: Return to work (RTW) is important for quality of life after breast cancer but its analysis at the population-level remains limited in France. This study aimed to implement Electronic Healthcare Data (EHD)-based indicators and trajectories to measure RTW after breast cancer diagnosis, and to examine stakeholders' perspectives regarding these indicators. METHODS: We followed a mixed-methods approach that consisted of (i) implementing RTW indicators and identifying clusters of trajectories using state sequence analysis with data from a representative sample of the French National Health Data System and (ii) exploring, through qualitative focus group and interviews, stakeholders' perceptions on the interpretation, limitations, and utility of these indicators. RESULTS: We extracted data from 317 women aged 25-55 years with a first diagnosis of early-stage breast cancer. The median number of sickness absence periods was 2 for a total of 434 days during the 3-year follow-up, and the median time to sustainable RTW was 240 days. Three clusters of RTW trajectories were identified: "early RTW" (49.5% of the population), "RTW after partial resumption" (37.5%) and "continuous compensation" (12.9%). Feedback from stakeholders highlighted the multi-factorial nature of RTW and underscored the added value of EHD for studying RTW, despite certain limitations. CONCLUSIONS: We demonstrated the feasibility of calculating RTW indicators and identifying trajectories using the French National Health Data System. These indicators can serve as outcome measures in RTW promotion and provide a basis for designing targeted interventions for breast cancer survivors.

Occupational, academic, and personal determinants of wellbeing and psychological distress in residents: results of a survey in Lyon, France.

Introduction: The mental health of residents is a growing significant concern, particularly with respect to hospital and university training conditions. Our goal was to assess the professional, academic, and psychological determinants of the mental health status of all residents of the academy of Lyon, France. Materials and methods: The Health Barometer of Lyon Subdivision Residents (BASIL) is an initiative which consists in proposing a recurrent online survey to all residents in medicine, pharmacy, and dentistry, belonging to the Lyon subdivision. The first of these surveys was conducted from May to July 2022. Participants should complete a series of validated questionnaires, including the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), and the Kessler Psychological Distress Scale (K6), respectively, and ad-hoc questions assessing their global health and hospital and academic working conditions. A Directed Acyclic Graph (DAG) analysis was conducted prior to multivariable analyses, to explore the determinants associated with low wellbeing (WEMWBS <43) and high psychological distress (K6 ≥ 13). Results: A total of 904 residents (response rate: 46.7%) participated in the survey. A low level of wellbeing was observed in 23% of participants, and was significantly associated to job strain (OR = 2.18; 95%CI = [1.32-3.60]), low social support (OR = 3.13; 95%CI = [2.05-4.78]) and the experience of very poor university teaching (OR = 2.51; 95%CI = [1.29-4.91]). A high level of psychological distress was identified for 13% of participants, and associated with low social support (OR = 2.41; 95%CI = [1.48-3.93]) and the experience of very poor university teaching (OR = 2.89, 95%CI = [1.16-7.21]). Conclusion: Hospital working conditions, social support, and the perception of teaching quality, were three major determinants of wellbeing and psychological distress among health profession residents. Demographic determinants, personal life and lifestyle habits were also associated. This supports a multilevel action in prevention programs aiming to enhance wellbeing and reduce mental distress in this specific population and local organizational specificities.