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Background Aging is one of the most important prognostic factors increasing the risk of clinical severity and mortality of COVID-19 infection. However, among patients over 75 years, little is known about post-acute functional decline. Objective The aim of this study was to identify factors associated with functional decline 3 months after COVID-19 onset, to identify long term COVID-19 symptoms and transitions between frailty statesafter COVID-19 onset in older hospitalized patients. Methods This prospective observational study included COVID-19 patients consecutively hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital. Functional decline, frailty status and long term symptoms were assessed at 3 month follow up. Functional status was assessed using the Activities of Daily Living simplified scale (ADL). Frailty status was evaluated using Clinical Frailty Scale (CFS). We performed multivariable analyses to identify factors associated with functional decline. Results Among the 318 patients hospitalized for COVID-19 infection, 198 were alive 3 months after discharge. At 3 months, functional decline occurred in 69 (36%) patients. In multivariable analysis, a significant association was found between functional decline and stroke (OR = 4,57, p  = 0,003), history of depressive disorder (OR = 3,05, p  = 0,016), complications (OR = 2,24, p  = 0,039), length of stay (OR = 1,05, p  = 0,025) and age (OR = 1,08, p  = 0,028). At 3 months, 75 patients described long-term symptoms (49.0%). Of those with frailty (CFS scores ≥5) at 3-months follow-up, 30% were not frail at baseline. Increasing frailty defined by a worse CFS state between baseline and 3 months occurred in 41 patients (26.8%). Conclusions This study provides evidence that both the severity of the COVID-19 infection and preexisting medical conditions correlates with a functional decline at distance of the infection. This encourages practitioners to establish discharge personalized care plan based on a multidimensional geriatric assessment and in parallel on clinical severity evaluation.

Background Cytomegalovirus (CMV) is associated with congenital infections that can lead to severe developmental and neurological complications in affected children. Daycare workers, who frequently interact with infants and young children, may be at higher risk of CMV infection. This study aims to investigate the rates of primary infection and reinfection of CMV among female daycare workers in the province of Québec, Canada to better understand the risk of occupational exposure in this population. Methods This mixed-method observational study protocol uses quantitative (prospective cohort) and qualitative (semi-structured interviews with daycare workers) components. Female daycare workers ( n  = 553) are recruited and enrolled in a prospective cohort study, with a non-daycare workers comparison group comprising hospital employees and plasma donors who do not have direct professional contact with children < 36 months of age (low-risk group, n  = 1659, 1:3 ratio). Participants are followed for 12 months, with blood for CMV serology, strain-specific antibody profiling with CMV-specific ELISA, CMV quantitative polymerase chain reaction (qPCR) and CMV-Scan assay collected from all participants at the first (V0) and last (V12) study visits. Among daycare workers and hospital employees, saliva samples are collected at these visits and monthly throughout the study for testing via CMV qPCR. Testing enables the identification of primary infections, reinfections, and reactivations, and estimates the association between demographic and occupational factors and CMV infection. Additionally, qualitative data is collected through interviews with daycare workers and daycare managers, focusing on their perceptions of CMV risks and current infection control practices. Discussion This study is expected to improve the understanding of CMV epidemiology among a high-risk group (i.e. female daycare workers). By estimating the incidence of CMV infections and patterns of viral shedding, the findings may inform occupational health strategies and public health policies. Based on our findings, guidelines aimed at preventing CMV infections could help protect not only daycare workers but also vulnerable populations, including young children and immunocompromised individuals, with whom they interact.

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system. We analyzed protein expression and activation of key players of the Akt/ mTOR pathway namely Akt, mTOR, and P70S6K in eleven A, B and AB thymomas as well as in normal thymuses. While only Akt and phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated in thymomas. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, we report the activation of Akt, mTOR and P70S6 proteins in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas. Finally, we showed that rapamycin (100 nM) significantly reduced proliferation of thymoma- derived epithelial cells without inducing cell death. Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities in rare thymic tumors.

ENTV (Enzootic Nasal Tumor Virus) and JSRV (Jaagsiekte Sheep Retrovirus) are β-retroviruses responsible for respiratory cancers in sheep and goats. In this study, we analyzed the genetic features of the sheep and goat β-Retroviruses (29 JSRV and 24 ENTV strains) circulating in France to identify molecular signatures associated with disease severity in flocks. We developed a highly specific PCR to amplify and sequence exogenous targeted regions or near full length proviruses based on limited discriminating motifs along their genomes. The phylogenetic reconstructions based on the Long Terminal Repeat (LTR) and regions suggest that one major strain is circulating on the French territory for ENTV-1 and ENTV-2 while not clustering with already published Spanish, Canadian or Chinese strains. JSRV strains circulating in French sheep flocks were distributed in 2 distinct genetic clades clustering with sequences originating from North America, Africa and United-Kingdom. JSRV clade I was found to be associated with a higher incidence of cancer in French flocks. Specific motifs spanning the entire JSRV genome particularly in the LTRs and in the intracytoplasmic domain of the envelope were detected between the two genetic subtypes. This work represents the first nationwide study describing the circulation of the three closely related β-oncogenic retroviruses JSRV, ENTV-1 and ENTV-2 in French sheep and goat flocks. Better characterization of strain genetics is a critical step in monitoring circulating - retroviruses, especially those associated with higher cancer incidence in small ruminants.

ObjectiveTo understand parental perspectives regarding universal newborn screening (UNS) for congenital cytomegalovirus (cCMV) in Canada.DesignA qualitative, patient-led study using the Patient and Community Engagement Research approach consisting of online focus groups and in-depth individual interviews to understand parental preferences regarding UNS for cCMV. Data were analysed iteratively using inductive thematic analysis and narrative story analysis.SettingCanada-wide study conducted via video conference from October to December 2023.Patients12 participants from five Canadian provinces who self-identified as 18 years of age or older and as having parental lived experience with cytomegalovirus (CMV) or cCMV participated in the study.ResultsWe identified three themes: (1) attitudes about UNS for cCMV, including participants’ unanimous support for UNS and confirmation that parental anxiety is not a deterrent for screening, (2) cCMV diagnosis, including the importance of coupling cCMV diagnosis with access to treatment and medical support and (3) awareness of cCMV, where participants shared their frustration about the lack of public and pregnant people’s awareness of cCMV.ConclusionsParental anxiety is not a deterrent for UNS for cCMV. Children with cCMV and their families deserve every opportunity to attain their best possible outcomes. UNS offers children with cCMV access to early intervention if they need it, and also helps to raise awareness and education to prevent future CMV infections.

AbstractJSRV (Jaagsiekte Sheep Retrovirus) is a retrovirus inducing a transmissible lung adenocarcinoma in sheep and goats with predominantly lepidic and papillary lesions. This naturally occurring lung cancer in large animals shares many features with human pneumonic-type lung adenocarcinomas with predominant lepidic growth. The metastatic spread is rare in both human and animal cancers. This unique feature prompted us to decipher the angiogenesis pathway in these cancers. We focused on the levels of mRNA and proteins of genes implicated in the extension of JSRV-induced lung adenocarcinomas by studying their expression in lung cancers (n = 10) and normal lungs (n = 10) and in primary epithelial alveolar type II cells derived from cancers (n = 10) or normal lungs (n = 6). In parallel, we evaluated the levels of expression of key genes in lung tissues collected from lepidic (n = 13) or papillary (n = 5) human adenocarcinomas and, when available, adjacent normal lungs (n = 11). We measured the expression of the same key genes implicated in angiogenesis, lymphangiogenesis and degradation of the extracellular matrix. In ovine adenocarcinomas, VEGFR2 and VEGFD mRNA were downregulated in cancers; MMP9, TIMP1 and FGFR2 mRNA were overexpressed as compared to normal lungs. Importantly, VEGFA and VEGFR2 proteins were not expressed in JSRV-induced cancers. In human lepidic adenocarcinomas, VEGFA and VEGFR2 mRNA were weakly expressed and no VEGFR2 protein was detectable. Downregulation of key angiogenic players may contribute to the control of extra thoracic invasion of cancer cells in human and ovine pneumonic-type adenocarcinoma with predominant lepidic growth.

Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32-7.87, p = 0.010), never-smoker status (OR = 3.57, 95% CI: 1.27-10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10-10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05-24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.

The Jaagsiekte sheep retrovirus exJSRV and its endogenous counterpart enJSRV co-exist in sheep. exJSRV, a betaretrovirus, is the etiological agent of ovine pulmonary adenocarcinoma, and it has been demonstrated in vitro that an enJSRV Gag variant bearing the R-to-W amino acid change at position 21 was able to block exJSRV budding from the cells, providing a potential protective role for the host. In this work, we developed a fast mutation detection assay based on the oligo ligation assay (OLA) that permits the quantification of the relative proportions of the R21 and W21 Gag variants present in individual genomes and in cDNA obtained from normal and exJSRV-induced lung tumors. We have shown that the W21/R21 ratio is variable within and between breeds. We also describe for the first time that putative protecting enJSRV variants were expressed in alveolar type II cells (AECII), the major target of exJSRV.

Cytomegalovirus (CMV) is associated with congenital infections that can lead to severe developmental and neurological complications in affected children. Daycare workers, who frequently interact with infants and young children, may be at higher risk of CMV infection. This study aims to investigate the rates of primary infection and reinfection of CMV among female daycare workers in the province of Québec, Canada to better understand the risk of occupational exposure in this population. This mixed-method observational study protocol uses quantitative (prospective cohort) and qualitative (semi-structured interviews with daycare workers) components. Female daycare workers (n = 553) are recruited and enrolled in a prospective cohort study, with a non-daycare workers comparison group comprising hospital employees and plasma donors who do not have direct professional contact with children < 36 months of age (low-risk group, n = 1659, 1:3 ratio). Participants are followed for 12 months, with blood for CMV serology, strain-specific antibody profiling with CMV-specific ELISA, CMV quantitative polymerase chain reaction (qPCR) and CMV-Scan assay collected from all participants at the first (V0) and last (V12) study visits. Among daycare workers and hospital employees, saliva samples are collected at these visits and monthly throughout the study for testing via CMV qPCR. Testing enables the identification of primary infections, reinfections, and reactivations, and estimates the association between demographic and occupational factors and CMV infection. Additionally, qualitative data is collected through interviews with daycare workers and daycare managers, focusing on their perceptions of CMV risks and current infection control practices. This study is expected to improve the understanding of CMV epidemiology among a high-risk group (i.e. female daycare workers). By estimating the incidence of CMV infections and patterns of viral shedding, the findings may inform occupational health strategies and public health policies. Based on our findings, guidelines aimed at preventing CMV infections could help protect not only daycare workers but also vulnerable populations, including young children and immunocompromised individuals, with whom they interact.