Nonreplicating synthetic mRNA vaccines: A journey through the European (Journal of Immunology) history.

The first worldwide article reporting that injections of synthetic nonreplicating mRNA could be used as a vaccine, which originated from a French team located in Paris, was published in the European Journal of Immunology (EJI) in 1993. It relied on work conducted by several research groups in a handful of countries since the 1960s, which put forward the precise description of eukaryotic mRNA and the method to reproduce this molecule in vitro as well as how to transfect it into mammalian cells. Thereafter, the first industrial development of this technology began in Germany in 2000, with the founding of CureVac, which stemmed from another description of a synthetic mRNA vaccine published in EJI in 2000. The first clinical studies investigating mRNA vaccines in humans were performed as collaboration between CureVac and the University of Tübingen in Germany as early as 2003. Finally, the first worldwide approved mRNA vaccine (an anti-COVID-19 vaccine) is based on the mRNA technologies developed by BioNTech since its 2008 foundation in Mainz, Germany, and earlier by the pioneering academic work of its founders. In addition to the past, present, and future of mRNA-based vaccines, the article aims to present the geographical distribution of the early work, how the development of the technology was implemented by several independent and internationally distributed research teams, as well as the controversies on the optimal way to design or formulate and administer mRNA vaccines.

PTSD and Partial PTSD among First Responders One and Five Years after the Paris Terror Attacks in November 2015.

Following the Paris terror attacks in November 2015, a large number of first responders (FR) were mobilized and consequently were at risk of developing posttraumatic stress disorder (PTSD). Based on the ESPA 13 November survey, the objectives of this study were to 1) describe the prevalence of PTSD and partial PTSD in FR five years after the attacks, 2) describe the changes in PTSD and partial PTSD from one to five years after the attacks, and 3) examine factors associated with PTSD and partial PTSD five years after the attacks. Data were collected using an online questionnaire. PTSD and partial PTSD were measured using the Post-Traumatic Stress Disorder Checklist based on the DSM-5 (PCL-5). Gender, age, responder category, education level, exposure, mental health history, history of traumatic events, training, social support, concern about the COVID-19 epidemic, and somatic problems present after the attacks were all analyzed as potential factors associated with PTSD and partial PTSD using multinomial logistic regression. A total of 428 FR were included 5 years after the attacks, of which 258 had participated also 1 year after the attacks. Five years after the attacks, the prevalence of PTSD and partial PTSD were 8.6% and 22%, respectively. Presence of somatic problems after the attacks were associated with PTSD. Involvement in dangerous crime scenes was associated with a higher risk of partial PTSD. No awareness of psychological risks in the context of professional activity through specific training was associated with partial PTSD, in particular among participants aged 45 years or more. To mitigate PTSD for FR, monitoring mental health symptoms, providing mental health education, and providing treatment may be needed for several years after the attacks.

Implementing Technologies: Assessment of Telemedicine Experiments in the Paris Region: Reasons for Success or Failure of the Evaluations and of the Deployment of the Projects.

BACKGROUND: Telemedicine is increasingly viewed as a tool to provide a wide range of health services. This article presents policy lessons drawn from the evaluation of telemedicine experiments conducted in the Paris region. METHODS: We used a mixed method design to study telemedicine projects commissioned by the Paris Regional Health Agency between 2013 and 2017. We combined data analysis of the telemedicine projects, review of the protocols, and interviews with stakeholders. RESULTS: We identified the following reasons for disappointing outcomes: the outcome measure was requested too early during the experiments because payers required information for budgetary decisions; and the learning curve, technical problems, diversion of use, insufficient number of inclusions, and a lack of adherence prevented the demonstration of successful outcomes of the projects. CONCLUSION: The evaluation of telemedicine should be undertaken after sufficient uptake to ensure barriers to implementation are overcome, and to obtain the sample size necessary for statistical power and reduce the average cost for one telemedicine request. Randomized controlled trials should be encouraged with appropriate funding and the follow-up period should be extended.

[Digital adaptation of a therapeutic education program in the context of Covid-19]. / Adaptation numérique d'un programme d'éducation thérapeutique dans le contexte de la Covid-19.

The context of containment due to the Covid-19 epidemic forced professionals to suspend their face-to-face therapeutic education programs. For young patients with asthma, the situation was made even more complex by anxiety-provoking communications (which turned out to be inaccurate) about the possible aggravating role of corticosteroids in the event of Covid-19, which led to untimely discontinuations and sometimes to a decrease in their therapeutic adherence, exposing them to an increased risk of poor control of their disease. Faced with the feeling of abandonment felt by some families in this singular context, a team at Trousseau Hospital in Paris decided to rethink and adapt its distance therapeutic education workshops.

Pregnancy, childbirth and postpartum experience in pregnant women infected with SARS-CoV-2 in 2020 in Paris: a qualitative phenomenological study.

BACKGROUND: The COVID-19 pandemic and the resulting lockdowns triggered social discontent on an unprecedented scale. Descriptive phenomenological studies showed that pregnant women were under intense stress during the COVID-19 outbreak, even though they remained uninfected. The purpose of this study was to report on the experiences of pregnant women affected by mild COVID-19 during the first wave of the pandemic. METHODS: In this non- interventional qualitative study, we analyzed pregnant women's experiences using an interpretive phenomenological analysis approach. We conducted semi-structured interviews with women who had had a mild COVID-19 during their pregnancy, and gave birth or planned to give birth in the maternity units of Sorbonne University in Paris, France. RESULTS: Participants reported that at the time they had COVID-19, they were not afraid of being seriously ill, but of transmitting COVID-19 to their close relatives. Their main concern was being pregnant and becoming a parent in a world where the pandemic deeply altered social environment. This included uncertainty about the future and an acute feeling of isolation related to lockdown. The idea that their partner might not be allowed to attend childbirth was almost unanimously felt as intolerable. In contrast, women had positive feelings regarding the fact that lockdown resulted in a de facto paternity leave leading to a certain degree of equality in the couple regarding baby care and household chores. Unexpectedly, the pandemic social distancing measures helped participants escaping from behavioral constraints, including the unspoken rule that they should welcome greetings from friends and family, despite being exhausted by the recent birth. CONCLUSIONS: Our results suggest that avoiding separation from their partner is a key to benevolent medical care for pregnant women in times of health crises. The unexpected benefits women reported in a world of lockdown cast a new light on their expectation regarding parenthood today.

A Descriptive Comparison of Mass Testing During the COVID-19 Pandemic in Montreal, Paris, Bamako, and Recife.

Objective: The aim of this descriptive article was to compare mass testing for SARS-CoV-2 during the first wave of the COVID-19 pandemic in Montreal, Canada; Bamako, Mali; Paris, France; and Recife, Brazil. Methods: Data was collected through interviews with key informants involved in the testing response and a review of the grey literature. The TIDieR-PHP checklist was then used to provide the basis of the intervention descriptions and to compare the data between cities. Results: Descriptive comparisons revealed that the type of test, the testing process, and materials used were similar between the cities during the first wave of the pandemic. In addition, all cities experienced similar material and personnel resource shortages, directly affecting testing accessibility and capacity. The main differences were related to testing capacity and implementation timelines, which were dependent on the state of the health care systems, governance, and access to resources. Conclusion: Results of this study highlight the similarities and differences in testing between the cities and demonstrate the importance of comprehensive intervention descriptions to highlight lessons learned, increase knowledge sharing, and inform policy decisions.

Abusive Head Trauma in Infants During the COVID-19 Pandemic in the Paris Metropolitan Area.

Importance: The COVID-19 pandemic and the containment and mitigation measures taken were feared to be associated with increased child abuse. Objective: To investigate the trend of abusive head trauma (AHT) incidence and severity in infants during the COVID-19 pandemic. Design, Setting, and Participants: In a time-series analysis of a longitudinal, population-based, cohort study, all consecutive cases of AHT in infants younger than 12 months old referred between January 2017 and December 2021 to Necker Hospital for Sick Children, the single regional pediatric neurosurgery center for the Paris metropolitan area, were included. AHT was defined as 1 or more subdural hemorrhage and a positive multidisciplinary evaluation after a social, clinical, biological, and radiological workup. Data were analyzed from January to March 2022. Main Outcomes and Measures: The primary outcome was the monthly incidence of AHT, which was analyzed using Poisson regression modeling. Secondary outcomes included mortality and severe morbidity and were studied with logistic and linear regressions. The monthly incidence of neurosurgical interventions for hydrocephalus was used as a control series. Results: Among the 99 included infants with AHT (median [IQR] age, 4 [3-6] months; 64 boys [65%]), 86 of 99 (87%) had bridging vein thrombosis, 74 of 99 (75%) had retinal hemorrhages, 23 of 72 (32%) had fractures, 26 of 99 (26%) had status epilepticus, 20 of 99 (20%) had skin injuries, 53 of 99 (54%) underwent neurosurgical interventions, and 13 of 99 (13%) died. Compared with the prepandemic period (2017-2019), AHT incidence was stable in 2020 (adjusted incidence rate ratio, 1.02; 95% CI, 0.59-1.77) and then significantly increased in 2021 (adjusted incidence rate ratio, 1.92; 95% CI, 1.23-2.99). The severity of AHT worsened in 2021 in terms of mortality (odds ratio 9.39; 95% CI, 1.88-47.00). Other secondary outcomes and the control series were not significantly modified. Conclusions and Relevance: In this cohort study, a marked increase in AHT incidence and severity occurred during the COVID-19 pandemic in the Paris metropolitan area. These results suggest the need for clinical awareness and preventive actions.

Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments : A Retrospective Cohort Study.

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.

Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study.

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Possible impact of the COVID-19 pandemic on the recreational use of nitrous oxide in the Paris area, France.

INTRODUCTION: Recreational use of nitrous oxide (N2O) is increasing in Western countries, including France. During the COVID-19 pandemic, some authors warned that recreational N2O use could increase further as the supply of illicit drugs was impacted by various containment measures. METHODS: We retrospectively analyzed N2O exposures reported to the Paris Poison Control Center (France) from 2010/01/01 to 2021/04/15. The Poison Severity Score was used to grade severity. RESULTS: During the study period, 93 cases of N2O recreational exposures were reported (male/female ratio: 1.1; median age: 20.9 years range: [14.8-49.0]). The first case was reported in 2012, 84/93 (90%) and 65/93 (70%) were reported since 2019 and March 17th 2020 (first lockdown in France) respectively. Most of the patients were symptomatic (88/93; 95%) and developed neurological symptoms (78/93; 84%). Among the fourteen patients who developed moderate to severe symptoms, eleven were reported after March 2020. CONCLUSION: Despite a marked increase in recreational N2O exposures during the COVID-19 pandemic, the exact impact of COVID-19 on this increase remains to be determined as it was observed from 2019.

Effects of COVID-19 Restriction Policies on Urban Heat Islands in Some European Cities: Berlin, London, Paris, Madrid, and Frankfurt.

The present study investigates the effects of policies restricting human activities during the COVID-19 epidemic on the characteristics of Night Land Surface Temperature (NLST) and Night Urban Heat Islands (NUHI) in five major European cities. In fact, the focus of this study was to explore the role of anthropogenic factors in the formation and intensity of NUHI. The effect of such factors was uncontrollable before the COVID-19 outbreak on the global scale and in a real non-laboratory environment. In this study, two indices, the concentration of Nitrogen dioxide (NO2) and Nighttime Lights (NL), were used as indicators of the number of anthropogenic activities. The data were collected before the COVID-19 outbreak and after its prevalence in 2019-2020. A Paired samples t-test and a Pearson correlation were used to examine the differences or significant relationships between the variables and indicators studied throughout the two periods. The results of the study confirmed a direct and significant relationship between NO2 and NL indices and the NUHI and NLST variables; however, using strict restrictions during the COVID-19 pandemic, the NO2 and NL indices decreased seriously, leading to significant changes in the characteristics of the NUHI and NLST in the five cities. This study has some implications for urban planners and politicians, e.g., the environmental impacts of changing the nature and level of anthropogenic activities can greatly affect the pattern and intensity of the Urban Heat Islands (UHIs) (as a serious environmental challenge).

Evolution of hospitalized patient characteristics through the first three COVID-19 waves in Paris area using machine learning analysis.

Characteristics of patients at risk of developing severe forms of COVID-19 disease have been widely described, but very few studies describe their evolution through the following waves. Data was collected retrospectively from a prospectively maintained database from a University Hospital in Paris area, over a year corresponding to the first three waves of COVID-19 in France. Evolution of patient characteristics between non-severe and severe cases through the waves was analyzed with a classical multivariate logistic regression along with a complementary Machine-Learning-based analysis using explainability methods. On 1076 hospitalized patients, severe forms concerned 29% (123/429), 31% (66/214) and 18% (79/433) of each wave. Risk factors of the first wave included old age (≥ 70 years), male gender, diabetes and obesity while cardiovascular issues appeared to be a protective factor. Influence of age, gender and comorbidities on the occurrence of severe COVID-19 was less marked in the 3rd wave compared to the first 2, and the interactions between age and comorbidities less important. Typology of hospitalized patients with severe forms evolved rapidly through the waves. This evolution may be due to the changes of hospital practices and the early vaccination campaign targeting the people at high risk such as elderly and patients with comorbidities.

[Social networks and confinement, a real impact on families]. / Réseaux sociaux et confinements, une réelle incidence sur les familles.

The various lockdowns linked to the Covid-19 epidemic have modified the use of communication tools, the Internet and social networks. In the context of the walk-in clinic or the child psychiatric evaluation interviews conducted at the Maison des adolescents of the Cochin Hospital in Paris, families were able to discuss the difficulties arising from this new use. Certain transgenerational, cultural and usual misunderstandings were discussed.

Assessing the Effectiveness of an Urban CO2 Monitoring Network over the Paris Region through the COVID-19 Lockdown Natural Experiment.

The Paris metropolitan area, the largest urban region in the European Union, has experienced two national COVID-19 confinements in 2020 with different levels of restrictions on mobility and economic activity, which caused reductions in CO2 emissions. To quantify the timing and magnitude of daily emission reductions during the two lockdowns, we used continuous atmospheric CO2 monitoring, a new high-resolution near-real-time emission inventory, and an atmospheric Bayesian inverse model. The atmospheric inversion estimated the changes in fossil fuel CO2 emissions over the Greater Paris region during the two lockdowns, in comparison with the same periods in 2018 and 2019. It shows decreases by 42-53% during the first lockdown with stringent measures and by only 20% during the second lockdown when traffic reduction was weaker. Both lockdown emission reductions are mainly due to decreases in traffic. These results are consistent with independent estimates based on activity data made by the city environmental agency. We also show that unusual persistent anticyclonic weather patterns with north-easterly winds that prevailed at the start of the first lockdown period contributed a substantial drop in measured CO2 concentration enhancements over Paris, superimposed on the reduction of urban CO2 emissions. We conclude that atmospheric CO2 monitoring makes it possible to identify significant emission changes (>20%) at subannual time scales over an urban region.

Nosocomial transmission clusters and lineage diversity characterized by SARS-CoV-2 genomes from two large hospitals in Paris, France, in 2020.

France went through three deadly epidemic waves due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing major public health and socioeconomic issues. We proposed to study the course of the pandemic along 2020 from the outlook of two major Parisian hospitals earliest involved in the fight against COVID-19. Genome sequencing and phylogenetic analysis were performed on samples from patients and health care workers (HCWs) from Bichat (BCB) and Pitié-Salpêtrière (PSL) hospitals. A tree-based phylogenetic clustering method and epidemiological data were used to investigate suspected nosocomial transmission clusters. Clades 20A, 20B and 20C were prevalent during the spring wave and, following summer, clades 20A.EU2 and 20E.EU1 emerged and took over. Phylogenetic clustering identified 57 potential transmission clusters. Epidemiological connections between participants were found for 17 of these, with a higher proportion of HCWs. The joint presence of HCWs and patients suggest viral contaminations between these two groups. We provide an enhanced overview of SARS-CoV-2 phylogenetic changes over 2020 in the Paris area, one of the regions with highest incidence in France. Despite the low genetic diversity displayed by the SARS-CoV-2, we showed that phylogenetic analysis, along with comprehensive epidemiological data, helps to identify and investigate healthcare associated clusters.