Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort.

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.

Suicidal ideation following self-reported COVID-19-like symptoms or serology-confirmed SARS-CoV-2 infection in France: A propensity score weighted analysis from a cohort study.

BACKGROUND: A higher risk of suicidal ideation associated with self-report of Coronavirus Disease 2019 (COVID-19)-like symptoms or COVID-19 infection has been observed in cross-sectional studies, but evidence from longitudinal studies remains limited. The aims of this study were 2-fold: (1) to explore if self-reported COVID-19-like symptoms in 2020 were associated with suicidal ideation in 2021; (2) to explore if the association also existed when using a biological marker of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 2020. METHODS AND FINDINGS: A total of 52,050 participants from the French EpiCov cohort were included (median follow-up time = 13.7 months). In terms of demographics, 53.84% were women, 60.92% were over 45 years old, 82.01% were born in mainland France from parents born in mainland France, and 59.38% completed high school. COVID-19-like symptoms were defined as participant report of a sudden loss of taste/smell or fever alongside cough, shortness of breath, or chest oppression, between February and November 2020. Symptoms were self-reported at baseline in May 2020 and at the first follow-up in Autumn 2020. Serology-confirmed SARS-CoV-2 infection in 2020 was derived from Spike protein ELISA test screening in dried-blood-spot samples. Samples were collected from October 2020 to March 2021, with 94.4% collected in 2020. Suicidal ideation since December 2020 was self-reported at the second follow-up in Summer 2021. Associations of self-reported COVID-19-like symptoms and serology-confirmed SARS-CoV-2 infection in 2020 with suicidal ideation in 2021 were ascertained using modified Poisson regression models, weighted by inverse probability weights computed from propensity scores. Among the 52,050 participants, 1.68% [1.54% to 1.82%] reported suicidal ideation in 2021, 9.57% [9.24% to 9.90%] had a serology-confirmed SARS-CoV-2 infection in 2020, and 13.23% [12.86% to 13.61%] reported COVID-19-like symptoms in 2020. Self-reported COVID-19-like symptoms in 2020 were associated with higher risks of later suicidal ideation in 2021 (Relative Riskipw [95% CI] = 1.43 [1.20 to 1.69]), while serology-confirmed SARS-CoV-2 infection in 2020 was not (RRipw = 0.89 [0.70 to 1.13]). Limitations of this study include the use of a single question to assess suicidal ideation, the use of self-reported history of mental health disorders, and limited generalizability due to attrition bias. CONCLUSIONS: Self-reported COVID-19-like symptoms in 2020, but not serology-confirmed SARS-CoV-2 infection in 2020, were associated with a higher risk of subsequent suicidal ideation in 2021. The exact role of SARS-CoV-2 infection with respect to suicide risk has yet to be clarified. Including mental health resources in COVID-19-related settings could encourage symptomatic individuals to care for their mental health and limit suicidal ideation to emerge or worsen.

Labor market participation and depression during the COVID-19 pandemic among young adults (18 to 30 years): A nationally representative study in France.

Objective: To examine the relationship between young adults' labor force participation and depression in the context of the COVID-19 pandemic. Design setting participants: Data come from the nationally-representative EPICOV cohort study set up in France, and were collected in 2020 and 2021 (3 waves of online or telephone interviews: 02/05/2020-12/06/2020; 26/10/2020-14/12/2020; 24/06/2021-09/08/2021) among 2,217 participants aged 18-30 years. Participants with prior mental health disorder (n = 50) were excluded from the statistical analyses. Results: Using Generalized Estimating Equation (GEE) models controlled for participants' socio-demographic and health characteristics and weighted to be nationally-representative, we found that compared to young adults who were employed, those who were studying or unemployed were significantly more likely to experience depression assessed using the PHQ-9 (multivariable ORs, respectively: OR: 1.29, 95% CI 1.05-1.60 and OR: 1.50, 1.13-1.99). Stratifying the analyses by age, we observed that unemployment was more strongly associated with depression among participants 25-30 years than among those who were 18-24 years (multivariable ORs, respectively, 1.78, 95% CI 1.17-2.71 and 1.41, 95% CI 0.96-2.09). Being out of the labor force was, to the contrary, more significantly associated with depression among participants 18-24 years (multivariable OR: 1.71, 95% CI 1.04-2.82, vs. 1.00, 95% CI 0.53-1.87 among participants 25-30 years). Stratifying the analyses by sex, we found no significant differences in the relationships between labor market characteristics and depression (compared to participants who were employed, multivariable ORs associated with being a student: men: 1.33, 95% CI 1.01-1.76; women: 1.19, 95% CI 0.85-1.67, multivariable ORs associated with being unemployed: men: 1.60, 95% CI 1.04-2.45; women: 1.47, 95% CI 1.01-2.15). Conclusions and relevance: Our study shows that in addition to students, young adults who are unemployed also experience elevated levels of depression in the context of the COVID-19 pandemic. These two groups should be the focus of specific attention in terms of prevention and mental health treatment. Supporting employment could also be a propitious way of reducing the burden of the COVID-19 pandemic on the mental health of young adults.

Time interval from last visit to imaging diagnosis influences outcome in pancreatic adenocarcinoma: A regional population-based study on linked medico-administrative and clinical data.

Background: Excessive waiting time intervals for the diagnosis and treatment of patients with pancreatic cancer can influence their prognosis but they remain unclear. The objective was to describe time intervals from the medical visit to diagnostic imaging and to treatment and their prognostic impact in pancreatic cancer in one French region. Methods: This retrospective observational multicentre study included all patients with pancreatic cancer seen for the first time in 2017 in multidisciplinary team meetings (MTMs), where clinical data were collected. A probabilistic matching with the medico-administrative data from the French national healthcare database (Système National des Données de Santé) was performed to define the care pathway from clinical presentation to the beginning of treatment. Median key time intervals were estimated for both resected and unresected tumours. Factors associated with 1-year survival were studied using Cox model. Results: A total of 324 patients (88% of total patients with MTM presentation) were matched and included: male 54%, mean age 72 years ±9.2, Eastern Cooperative Oncology Group (ECOG) PS > 1 19.5%, metastatic disease at diagnosis 47.4%, tumour resection 16%. At 1 year, 57% had died (65% in the unresected group and 17% in the resected group). The median time interval from the medical visit to diagnostic imaging was 15 days [Q1-Q3: 8-44]. After imaging, median time intervals to definite diagnosis and to first treatment were 11 and 20 days, respectively. Significant prognostic factors associated with the risk of death at 1 year were ECOG PS > 1 (hazard ratio (HR) 2.1 [1.4-3.0]), metastasis (HR 2.7 [1.9-3.9]), no tumour resection (HR 2.7 [1.3-5.6]) and time interval between the medical visit and diagnostic imaging ⩾25 days (HR 1.7 [1.2-2.3]). Conclusion: Delay in access to diagnostic imaging impacted survival in patients with pancreatic cancer, regardless of whether tumour resection had been performed.

Impact of Novel Hormonal Agents (Abiraterone, Enzalutamide) on the Development of Visceral and/or Brain Metastases in Patients With Bone-metastatic Castration-resistant Prostate Cancer.

INTRODUCTION: The overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients has improved since 2011 with the use of novel hormonal agents (NHAs). The incidence of brain metastases (mets) has been reported to increase since 2004 with the use of docetaxel, but not the incidence of visceral mets. Our objective was to study whether the use of NHAs increases the risk of developing visceral or brain mets (VBMs). PATIENTS AND METHODS: mCRPC patients with mets limited to bone (bmCRPC), treated at Tours University Hospital between 2007 and 2015, were included retrospectively. The primary endpoint was to determine whether treatment with NHAs was associated with an increased incidence of VBMs. Secondary endpoints included the search for putative predictive factors to develop VBMs. RESULTS: On 187 bmCRPC patients included, 65 developed VBMs. VBM incidence increased in bmCRPC patients alive after 2011, compared to patients who died before (39.7 vs. 24.6%, P = .04). Meanwhile, their median OS increased from 16.3 months to 28.5 months (P = .01). The longer was the treatment with NHAs, the lower was the risk of VBMs (HR = 0.96, 95% CI [0.94; 0.99]), whereas age < 70 years (HR = 3.33, 95% CI [1.50; 7.40]) and low PSA level at diagnosis (HR = 1.58, 95% CI [1.16; 2.15]) increased this risk. CONCLUSION: Though retrospective, our results showed an increased incidence of VBMs in bmCRPC patients after 2011. However, this was not associated with NHA exposure duration. The role of NHA exposure remains unclear and needs further investigation.

Differentiating PNES from epileptic seizures using conversational analysis on French patients: A prospective blinded study.

Psychogenic nonepileptic seizures (PNES) resemble epileptic seizures (ES) but are not caused by the occurrence of excessive cortical neuronal discharge. Previous studies in German-, English-, and Italian-speaking patients showed that patients used a different communicative style to talk about their seizures. They demonstrated that the diagnosis between PNES and ES could be predicted using qualitative assessment and a diagnostic scoring aid (DSA). The objective of our study was to evaluate the contribution of linguistic analysis in the differential diagnosis between ES and PNES in a French patient population. During an extended video-electroencephalogram (video-EEG) monitoring, 13 patients presented PNES and 19 patients with ES. Two neurologists blindly and independently analyzed the interview of each patient. Rater 1 predicted the correct diagnosis in 27 of 32 patients (84%) and Rater 2 in 28 of 32 patients (88%). Interrater reliability of qualitative analysis was satisfactory (k = 0.68, interrater agreement = 84.4%). Using a simplified DSA, Rater 1 and Rater 2 would have correctly diagnosed 88% (28/32 patients) and 91 % (29/32) of the cases, respectively. Our blinded prospective study confirms the diagnostic value of conversational analysis, performed by neurologists, to differentiate PNES from ES in French-speaking patients.