Contribution of real-life studies in France during the COVID-19 pandemic and for the national pharmaco-epidemiological surveillance of COVID-19 vaccines.

During the COVID-19 pandemic, EPI-PHARE, a scientific group in pharmaco-epidemiology created by the French National Agency for the Safety of Medicines and Health Products (ANSM) and the French National Health Insurance (Cnam), has reoriented its work program to enlighten health authorities in this health crisis. By exploiting massive and complex data of the French Health Data System (SNDS) from the beginning of the first lockdown in France in March 2020, we were able to publish numerous results on the use, benefits and risks of medicines, on the risk factors of COVID-19 before and after vaccination, and on the benefits and risks of COVID-19 vaccines. Our results were widely taken into account by the French health authorities and allowed them to take informed decision in this pandemic situation in order to ensure the health of the population.

Does Measles, Mumps, and Rubella (MMR) Vaccination Protect against COVID-19 Outcomes: A Nationwide Cohort Study.

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.

Hospitalization for COVID-19 is associated with a higher risk of subsequent hospitalization for psychiatric disorders: A French nationwide longitudinal study comparing hospitalizations for COVID-19 and for other reasons.

INTRODUCTION: Although COVID-19 has been associated with psychiatric symptoms in patients, no study to date has examined the risk of hospitalization for psychiatric disorders after hospitalization for this disease. OBJECTIVE: We aimed to compare the proportions of hospitalizations for psychiatric disorders in the 12 months following either hospitalization for COVID-19 or hospitalization for another reason in the adult general population in France during the first wave of the current pandemic. METHODS: We conducted a retrospective longitudinal nationwide study based on the national French administrative healthcare database. RESULTS: Among the 2,894,088 adults hospitalized, 96,313 (3.32%) were admitted for COVID-19. The proportion of patients subsequently hospitalized for a psychiatric disorder was higher for COVID-19 patients (11.09 vs. 9.24%, OR = 1.20 95%CI 1.18-1.23). Multivariable analyses provided similar results for a psychiatric disorder of any type and for psychotic and anxiety disorders (respectively, aOR = 1.06 95%CI 1.04-1.09, aOR = 1.09 95%CI 1.02-1.17, and aOR = 1.11 95%CI 1.08-1.14). Initial hospitalization for COVID-19 in intensive care units and psychiatric history were associated with a greater risk of subsequent hospitalization for any psychiatric disorder than initial hospitalization for another reason. DISCUSSION: Compared with hospitalizations for other reasons, hospitalizations for COVID-19 during the first wave of the pandemic in France were associated with a higher risk of hospitalization for a psychiatric disorder during the 12 months following initial discharge. This finding should encourage clinicians to increase the monitoring and assessment of psychiatric symptoms after hospital discharge for COVID-19, and to propose post-hospital care, especially for those treated in intensive care.

Characteristics associated with the residual risk of severe COVID-19 after a complete vaccination schedule: A cohort study of 28 million people in France.

Background: Prior to the availability of vaccines, the risk factors for developing severe forms of COVID-19 were mostly older age and various comorbidities such as diabetes, cardiovascular diseases, mental disorders, transplantations, and kidney disease. Although vaccines have been shown to be highly effective in preventing severe forms of COVID-19, a residual risk may persist, despite vaccination, for certain population groups. Methods: The study was based on data from the national COVID-19 vaccination database (VAC-SI) coupled with the National Health Data System (SNDS), which contains comprehensive reimbursement and hospitalisation data for all of France. All people fully vaccinated by July 31, 2021, with a double-injection vaccine, i.e., the mRNA BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 vaccines, or a single dose for people with a previous confirmed SARS-CoV-2 infection were included and followed until August 31, 2021. Cox proportional hazard models were performed to estimate adjusted hazard ratios (aHR) for COVID-19-related hospitalisation or in-hospital death associated with age, gender, deprivation index, comorbidities, and immunosuppressive or oral corticosteroid therapy from day 14 after full-vaccination. Findings: In a population of 28,031,641 fully vaccinated individuals with an average follow-up of 80 days, 5,345 (87 hospitalisations per 100,000 person-years) were hospitalised for COVID-19 and 996 (16 in-hospital death per 100,000 person-years) died in hospital. In multivariable analysis, a higher risk was observed with increasing age, male gender, and social deprivation. Most of the 47 chronic conditions considered were positively associated with an increased risk of COVID-19-related hospitalisation and a slight excess risk of death. The risk of hospitalisation and in-hospital death for COVID-19 also increased with the use of immunosuppressants (aHR 3.3 [2.8-3.8] and 2.4 [1.7-3.5], respectively) and oral corticosteroids (aHR 2.8 [2.5-3.1] and 4.1 [3.3-5.1]).Less than 10% (519/5,345) of hospitalised cases and 2% (24/996) of those who died in hospital had no identified comorbidities. There was a strong association between an increasing number of comorbidities and the risk of hospitalisation and in-hospital death (e.g., 5+ versus none, aHR 10.1 95%CI 9.0-11.5 and 17.8 95%CI 11.5-27.4, respectively). Interpretation: Although vaccination has dramatically reduced the occurrence of severe forms of COVID-19, a residual risk remains for the elderly, immunocompromised, and polypathological populations and warrants complementary preventive measures. Funding: None.

Outpatient Antibiotic Prescriptions in France: Patients and Providers Characteristics and Impact of the COVID-19 Pandemic.

In France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets for future public health actions. Using data from the French National Health Data System, we described and compared the individual characteristics of patients with and without an antibiotic prescription. The prescribed antibiotics (ATC-J01) were detailed and compared between 2019 and 2020. Antibiotic prescribing indicators that take prescriber activity into account were estimated and compared. Patients who were female, advanced age, and the presence of comorbidities were associated with antibiotic prescriptions. The overall prescription rate was estimated at 134 per 1000 consultations and 326 per 1000 patients seen in 2019. General practitioners (GPs), dentists and paediatricians were associated with 78.0%, 12.2% and 2.2% of antibiotic prescriptions, respectively, with high prescription rates (391, 447, and 313 p. 1000 patients seen, respectively). In comparison with 2019, this rate decreased in 2020 for paediatricians (-30.4%) and GPs (-17.9%) whereas it increased among dentists (+17.9%). The reduction was twice as high among the male prescribers than among their female counterparts (-26.6 and -12.0, respectively). The reduction in prescriptions observed in 2020 (-18.2%) was more marked in children (-35.8%) but less so among individuals ≥65 years (-13.1%) and those with comorbidities (-12.5%). The decrease in penicillin prescriptions represents 67.3% of the overall reduction observed in 2020. The heterogeneous decrease in prescriptions by age and antibiotic class could be explained by the impact of COVID-19 control measures on the spread of respiratory viruses; thus, a substantial proportion of the prescriptions avoided in 2020 is likely inappropriate, particularly among children. In order to keep the rate of prescriptions comparable to that observed in 2020, male prescribers, paediatricians and GPs should be encouraged to maintain that level, while a campaign to raise awareness of the appropriate use of antibiotics should be aimed at dentists in particular.