Importance: Solid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19–related severity in this population are still insufficiently explored in the literature.Objective: To examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19–related hospitalization in solid organ transplant recipients.Design, Setting, and Participants: Using the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022.Exposures: Immunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities).Main Outcomes and Measures: The main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately.Results: Overall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients.Conclusions and Relevance: This study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19–related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.

Objective: To assess the risk of intracranial meningioma associated with oral contraceptives containing desogestrel, levonorgestrel, or levonorgestrel combined with oestrogen. Design: Case-control study. Setting: French national health data system (Système National des Données de Santé). Participants: 8391 women living in France who required surgery for intracranial meningioma in 2020-23. Each patient was matched to 10 women without intracranial meningioma (controls) on year of birth and area of residence. Main outcome measure: Risk of intracranial meningioma associated with oral contraceptives containing desogestrel 75µg, levonorgestrel 30µg, or levonorgestrel 50-150 µg combined with oestrogen, and duration of use: short term use was defined by one or more dispensations within the year before the index date only, and prolonged use was defined by continuous use of one year or more (up to seven or more years of continuous use). Conditional logistic regression was used to calculate odds ratios. Results: 92 301 women, mean age 59.7 years (standard deviation 12.9 years), were included. Among 8391women who had undergone surgery for intracranial meningioma, 287 (3.4%) used desogestrel 75µg ( v 2769/83 910 (3.3%) controls), 17 (0.2%) used levonorgestrel 30 µg ( v 140 (0.2%)), and 157 (1.9%) used levonorgestrel combined with oestrogen ( v 1933 (2.3%)). In analyses of desogestrel according to duration of use, the odds ratio for risk of intracranial meningioma for short term use was 1.02 (95% confidence interval 0.77 to 1.34) and for prolonged use was 1.32 (1.14 to 1.53). Risk was driven by more than five continuous years of use: odds ratio 1.51 (1.17 to 1.94) for five to seven years and 2.09 (1.51 to 2.90) for ≥7 years. Excess risk was greater in women with meningiomas located in the middle or anterior part of the skull base (1.90 (1.47 to 2.46) and 1.50 (1.17 to 1.93), respectively) and in those who had previously used a progestogen of known associated increased risk (3.30 (2.64 to 4.11)). Results showed no excess risk of intracranial meningioma for levonorgestrel (alone or combined with oestrogen) regardless of duration of use. The estimated number needed to harm with desogestrel was 67 300 women for one intracranial meningioma requiring surgery. Risk was no longer observed one year after discontinuation of desogestrel. Conclusions: The results showed a small increased risk of intracranial meningioma in women who had used desogestrel 75 µg for more than five continuous years, but no risk in users of levonorgestrel (alone or combined with oestrogen).

Cross-protection from previous live attenuated vaccines is proposed to explain the low impact of COVID-19 on children. This study aimed to evaluate the effect of live attenuated MMR vaccines on the risk of being hospitalized for COVID-19 in children. An exposed (MMR vaccine)–non-exposed cohort study was conducted using the nationwide French National Health Data System (SNDS). We included children born between 1 January 2009 and 31 December 2019. Exposure was defined as a claim of at least one dose of MMR vaccine since birth. Hospitalization for COVID-19 was defined using main diagnostic ICD10 codes. Non-conditional logistic regression was used to calculate the adjusted odds ratios (aORs) of the association between MMR exposure and hospitalization for COVID-19, controlling for socio-demographic and socio-economic factors, co-morbidities, and general health. In total, 6,800,542 (median age 6 IQR [3–8] years) children exposed to a MMR vaccine and 384,162 (6 [3–9] years) not exposed were followed up with for 18 months. Among them, 873 exposed to the MMR vaccine and 38 who were not exposed were hospitalized for COVID-19. In a multi-variate analysis, the exposure of children to MMR vaccination was not associated with a decreased risk of COVID-19 hospitalization versus non-exposure (aOR (95%CI) = 1.09 [0.81–1.48]). A stratified analysis by age showed an aOR = 1.03 [0.64–1.66] for children aged 1–4, an aOR = 1.38 [0.82–2.31] for those aged 5–9, and an aOR = 1.11 [0.54–2.29] for those aged 10–12. Our study suggests that the live attenuated MMR vaccine does not protect children against COVID-19 hospitalization.

En 2019, les premiers cas de la maladie à Coronavirus (COVID-19) sont identifiés chez l'humain à Wuhan en Chine. Elle a évolué très vite vers une pandémie mondiale en 2020. Certains facteurs de risque (âge, sexe, comorbidités…) sont décrits comme associés à la sévérité de la maladie. En 2021, les premiers vaccins sont rendus disponibles et entrainent une baisse significative des formes sévères. Cependant, ces principaux facteurs ci-dessus ont été insuffisamment explorés dans certaines populations telles que les enfants et les immunodéprimés qui ont des spécificités différentes de la population générale. L'objectif général de notre thèse était d'étudier les facteurs associés au risque d'hospitalisation pour COVID-19 en particulier des vaccins existants proposés comme potentiellement protecteur contre la forme hospitalisée de la COVID-19 et des médicaments immunosuppresseurs dans certaines populations spécifiques en utilisant les données du Système National des Données de Santé (SNDS). Notre première étude basée sur une large cohorte d'enfants âgés de 1 à 12 ans a montré que le vaccin Rougeole-Oreillons-Rubéole proposé par certains auteurs pour expliquer le faible nombre de cas sévères chez les enfants n'était pas associé à une diminution du risque d'hospitalisation. Notre deuxième étude, descriptive de la vaccination anti-SARS-CoV-2 chez l'enfant a montré que 283860 enfants de 5 à 11 ans avaient reçu une délivrance de vaccin contre la COVID-19 entre 2021 et 2022, soit seulement 4,6% de cette population en France. Des disparités régionales dans la couverture vaccinale, la faible représentation des enfants atteints de comorbidités et le niveau socioéconomique élevé parmi les vaccinés ont été rapportées. Notre troisième étude a permis de mesurer l'impact des médicaments immunosuppresseurs indiqués dans le rejet de greffe sur le risque d'hospitalisation pour COVID-19 chez les transplantés d'organes. Nous avons montré que les corticoïdes et l'acide mycophénolique sont associés à un sur-risque d'hospitalisation, le tacrolimus et la ciclosporine chez les transplantés hépatiques et cardiaques sont associés à un risque réduit d'hospitalisation, comparés aux autres médicaments immunosuppresseurs. Dans l'ensemble, nos travaux peuvent contribuer à alimenter les décideurs en données qui aideraient à améliorer les mesures de santé publique et la prise en charge des enfants et des greffés alors que la pandémie se poursuit. Ce travail a permis aussi d'établir des cohortes bien identifiées et validées d'enfants et de greffés et de développer des outils méthodologiques (algorithmes d'identification de facteurs de confusion, d'exposition aux vaccins, d'expositions aux immunosuppresseurs, de date index etc.) qui pourront être utilisés dans d'autres évaluations soit de ces populations soit de ces expositions.