Protection of COVID-19 Vaccination Against Hospitalization During the Era of Omicron BA.4 and BA.5 Predominance: A Nationwide Case-Control Study Based on the French National Health Data System.

Background: Knowing the duration of effectiveness of coronavirus disease 2019 (COVID-19) booster doses is essential to providing decision-makers with scientific arguments about the frequency of subsequent injections. We estimated the level of protection against COVID-19-related hospitalizations (Omicron BA.4-BA.5) over time after vaccination, accounting for breakthrough infections. Methods: In this nationwide case-control study, all cases of hospitalizations for COVID-19 identified in the comprehensive French National Health Data System between June 1, 2022, and October 15, 2022, were matched with up to 10 controls by year of birth, sex, department, and an individual COVID-19 hospitalization risk score. Conditional logistic regressions were used to estimate the level of protection against COVID-19-related hospitalizations conferred by primary and booster vaccination, accounting for history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: A total of 38 839 cases were matched to 377 653 controls; 19.2% and 9.9% were unvaccinated, respectively, while 68.2% and 77.7% had received ≥1 booster dose. Protection provided by primary vaccination reached 45% (95% CI, 42%-47%). The incremental effectiveness of booster doses ranged from 69% (95% CI, 67%-71%; ≤2 months) to 22% (95% CI, 19%-25%; ≥6 months). Specifically, the second booster provided an additional protection compared with the first ranging from 61% (95% CI, 59%-64%; ≤2 months) to 7% (95% CI, 2%-13%; ≥4 months). Previous SARS-CoV-2 infection conferred a strong, long-lasting protection (51% ≥20 months). There was no incremental effectiveness of a second booster among individuals infected since the first booster. Conclusions: In the era of Omicron BA.4 and BA.5 predominance, primary vaccination still conferred protection against COVID-19 hospitalization, while booster doses provided an additional time-limited protection. The second booster had no additional protection in case of infection since the first booster.

Impact of coronavirus disease 2019 on contraception use in France.

To limit the spread of the coronavirus disease 2019 (COVID 19), sanitary restrictions have been established since March 2020 in France. These restrictions and the waves of contamination may have had consequences on the use of health products in general, and on the use of contraceptives in particular. We aimed to assess the impact of COVID 19 pandemic from March 16th 2020 to April 30th 2021 in France on reimbursed contraceptives. We analyzed data from the French national health insurance database (SNDS) by extracting all oral contraception (OC), emergency contraception (EC), levonorgestrel-intrauterine system (LNG-IUS), copper-intrauterine device (C-IUD) and contraceptive implant dispensations in 2018, 2019, 2020 and to April 30th 2021. We computed the expected use of contraceptives in 2020 and 2021 without pandemic and its associated sanitary restrictions, by taking the annual trend into account. We assessed the evolution of dispensations by type of contraceptive and by age-groups (≤25 years old, between 25 and 35 and >35 years old) between observed and expected dispensations. After 15 months of pandemic, a decrease of all reimbursed contraceptives dispensations had been estimated, compared with what was expected: -2.0% for OC, -5.0% for EC, -9.5% for LNG-IUS, -8.6% for C-IUD, -16.4% for implant. Women under 25 years old were the most impacted by the decrease. This national study showed that the impact of the COVID 19 crisis was global on all reimbursed contraceptives, with different levels of impact depending on the type of contraceptive, the age-group and the severity of the restriction. OC dispensing decreased marginally compared with expectations. The decrease in long-acting contraceptives dispensing was more pronounced, especially for the implant. These results call for continued monitoring of contraceptive use over the long term and for prioritizing access to sexual health services during crises, especially among the youngest women who were most affected in this study.

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.

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.

Impact of Coronavirus disease 2019 (COVID-19) on contraception use in 2020 and up until the end of April 2021 in France.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on the use of reimbursed contraceptives in France after 15 months of the pandemic, according to age-group and updating previous data only pertaining to the first lockdown (2 months). STUDY DESIGN: We conducted a national register-based study by extracting all reimbursements of oral contraceptives (OC), emergency contraception (EC), intrauterine devices (IUD), and implants from the French National Health Insurance database (SNDS), which includes and covers 99.5% of the French population, in 2018, 2019, 2020 and from January 1, 2021 to April30, 2021. We calculated the expected use of contraceptives in 2020 and 2021 in the absence of the pandemic, based on 2018 and 2019 usage and taking annual trends into account. We assessed the difference between observed and expected dispensing rates by contraceptive type and by age-group (≤18 years old, 18< age ≤25, 25< age ≤35, >35). RESULTS: Dispensing of all contraceptives decreased compared to expect dispensing numbers: -2.0% for OC, -5.3% for EC, -9.5% for LNG-IUS, -8.6% for C-IUD, and -16.4% for implant. This decrease in the dispensing of contraceptives was observed in all age-groups, but mainly concerned women under the age of 18 years (-22% for OC, -10% for EC, -37.2% for LNG-IUS, -36.4% for C-IUD, -26.4% for implant) and those aged 18 to 25 (-5.1% for OC, -11.9% for EC, -18.1% for LNG-IUS, -15.9% for C-IUD, -17.6% for implants). CONCLUSIONS: Our study showed that the dispensing of contraceptives in France was markedly impacted by the COVID-19 pandemic. Prescriptions for long-acting contraceptive use and women under the age of 25 years were the most substantially impacted. Ensuring access to contraceptive methods during health emergencies must be a public health policy priority. IMPLICATIONS: The COVID-19 pandemic strongly impacted the dispensing of contraceptives in France with varying degrees of decreased dispensing according to the type of contraceptive, the age-group and the level of pandemic-related restrictions. The impact of these restrictions on unintended pregnancy at the population level remains undetermined.

Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people.

BACKGROUND: From the beginning of the COVID-19 pandemic, age (most importantly), male gender and various comorbidities were found to be associated with severe forms of COVID-19. However, there was little information provided for an entire country such as France, which was severely affected throughout the epidemic. METHODS: In France, the SNDS, comprising all health insurance reimbursements and benefits, and the PMSI, comprising hospital data, can be used to estimate the risk associated with about fifty diseases or health conditions for hospitalization primarily related to COVID-19 and COVID-19-related deaths. A cohort was constituted comprising all people alive on February 15, 2020. Data were censored at 15 June 2020 for COVID-19-related hospitalization and at 15 July 2020 for death for patients still hospitalized for COVID-19 on 15 June 2020. Cox proportional hazards models were used to estimate hazard ratios (HR) for the associations between each comorbidity (n=47) and the risk of COVID-19-related hospitalization or death. These associations were determined with adjustment for age and gender, and then in models including all variables (adjusted hazard ratios [aHR]). FINDINGS: In a population of 66,050,090 people, 87,809 people (134 per 100,000) were hospitalized for COVID-19 between February 15, 2020 and June 15, 2020 and a subgroup of 15,661 people (24 per 100,000) died in hospital.A much higher risk was observed with increasing age, reaching a risk of hospitalization for COVID-19 more than five fold higher and a risk of COVID-19-related in-hospital mortality more than 100-fold higher in people aged 85 years and older (absolute risks of 750 and 268 per 100,000, respectively) compared to people aged 40 to 44 years.Men were at higher risk of COVID-19-related hospitalization aHR 1.38 [1.36-1.40]) and COVID-19-related in-hospital mortality (aHR 2.08 [2.01-2.16]) compared to women. Positive associations between social deprivation index and risk of COVID-19 were also observed. Almost all chronic health conditions were positively associated with an increased risk of COVID-19-related hospitalization and in-hospital mortality, with the exception of dyslipidaemia, which was negatively associated. The strongest associations for both COVID-19-related hospitalization and in-hospital mortality were observed in people with Down syndrome (7.0 [6.1-8.1] and 22.9 [17.1-30.7], respectively), mental retardation (3.8 [3.5-4.2] and 7.3 [6.1-8.8], respectively), kidney transplantation (4.6 [4.2-5.0] and 7.1 [6.0-8.4], respectively), lung transplantation (3.5 [2.4-5.3] and 6.2 [2.8-14.0], respectively) end-stage renal disease on dialysis (4.2 [3.9-4.4] and 4.7 [4.2-5.2], respectively) and active lung cancer (2.6 [2.4-2.8] and 4.0 [3.5-4.6], respectively). INTERPRETATION: This national cohort study confirms the associations with most diseases and health conditions in France and provides data on less frequent health conditions, which could be useful particularly to target priority populations during present and future vaccination campaigns. FUNDING: None.

Antihypertensive Drugs and COVID-19 Risk: A Cohort Study of 2 Million Hypertensive Patients.

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Standardization and Validation of Fluorescence-Based Quantitative Assay to Study Human Platelet Adhesion to Extracellular-Matrix in a 384-Well Plate.

Platelets play a crucial role in the immunological response and are involved in the pathological settings of vascular diseases, and their adhesion to the extracellular matrix is important to bring leukocytes close to the endothelial cells and to form and stabilize the thrombus. Currently there are several methods to study platelet adhesion; however, the optimal parameters to perform the assay vary among studies, which hinders their comparison and reproducibility. Here, a standardization and validation of a fluorescence-based quantitative adhesion assay to study platelet-ECM interaction in a high-throughput screening format is proposed. Our study confirms that fluorescence-based quantitative assays can be effectively used to detect platelet adhesion, in which BCECF-AM presents the highest sensitivity in comparison to other dyes.

Synthesis, characterization, and x-ray crystal structures of cyclam derivatives. 8. Thermodynamic and kinetic appraisal of lead(II) chelation by octadentate carbamoyl-armed macrocycles.

En route toward the development of hybrid organic-inorganic extracting materials incorporating lead-selective chelators and their implementation in water purification processes, the lead(II) binding properties of three N-carbamoylmethyl-substituted 1,4,8,11-tetraazacyclotetradecanes (cyclams) have been fully investigated by spectroscopic (IR, UV-vis, MALDI-TOF MS, (1)H and (13)C NMR), X-ray crystallographic, potentiometric, and kinetic methods. Solution NMR studies revealed that the Pb(2+) ion is entrapped in a molecular cage constituted by the four macrocyclic nitrogen and four amidic oxygen atoms. Protonation and lead binding constants determined in aqueous solution were shown to be linearly dependent, so that all three derivatives possess a similar affinity at any pH value. Thermodynamic and kinetic parameters revealed the crucial role played by the intramolecular hydrogen bonds also evidenced in the crystal structure of the tetraacetamide derivative L(1), which involve the lone pair of each macrocyclic tertiary amine and one amidic hydrogen atom belonging to the appended arm. In contrast to L(1), the absence of such intramolecular interactions for N-(dimethyl)carbamoylmethyl- and N-(diethyl)carbamoylmethyl-substituted cyclams (L(2) and L(3), respectively) accounts for the 2-3 orders of magnitude enhancement of their proton and lead binding affinities. Stopped-flow kinetic measurements enabled unraveling the formation process of the three lead(II) complexes that proceeds in a single rate-limiting step according to the Eigen-Winkler mechanism, while the apparent rate constants were found to increase in the order L(3) < L(2) << L(1) as a consequence of the more acidic character of L(1). A common proton-assisted dissociation mechanism has been found for the three lead(II) complexes, which involves the rapid formation of a protonated, six-coordinate intermediate followed by either a unimolecular decomposition or a bimolecular attack of a second hydronium ion.