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International audience; Corona-Virus Disease (COVID-19), caused by the novel Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) has been spreading rapidly worldwide causing the world to face a global health crisis. Countries are experiencing a new wave of contamination and are witnessing spikes in the disease without being able to control its spread again. This paper aims to analyze the mortality rate related to the COVID-19 pandemic infection in Tunisia and to assess the effectiveness of health control policies. Data collection for this document was stopped on October, 31 st , 2020.

International audience; Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.

Recent studies based on observations have shown the impact of lockdown measures taken in various European countries to contain the Covid-19 pandemic on air quality. However, these studies are often limited to compare situations without and with lockdown measures, which correspond to different time periods and then under different meteorological conditions. We propose a modelling study with the WRF-CHIMERE modelling suite for March 2020, an approach allowing to compare atmospheric composition with and without lockdown measures without the biases of meteorological conditions. This study shows that the lockdown effect on atmospheric composition, in particular through massive traffic reductions, has been important for several short-lived atmospheric trace species, with a large reduction in NO2 concentrations, a lower reduction in Particulate Matter (PM) concentrations and a mitigated effect on ozone concentrations due to non-linear chemical effects. Highlights • Air pollution modelling • COVID19 epidemy • Regional modelling • Anthropogenic emissions scenario • Impact of emissions reduction Graphical abstract Unlabelled Image

International audience; On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak as a pandemic, with over 720,000 cases reported in more than 203 countries as of 31 March. The response strategy included early diagnosis, patient isolation, symptomatic monitoring of contacts as well as suspected and confirmed cases, and public health quarantine. In this context, telemedicine, particularly video consultations, has been promoted and scaled up to reduce the risk of transmission, especially in the United Kingdom and the United States of America. Based on a literature review, the first conceptual framework for telemedicine implementation during outbreaks was published in 2015. An updated framework for telemedicine in the COVID-19 pandemic has been defined. This framework could be applied at a large scale to improve the national public health response. Most countries, however, lack a regulatory framework to authorize, integrate, and reimburse telemedicine services, including in emergency and outbreak situations. In this context, Italy does not include telemedicine in the essential levels of care granted to all citizens within the National Health Service, while France authorized, reimbursed, and actively promoted the use of telemedicine. Several challenges remain for the global use and integration of telemedicine into the public health response to COVID-19 and future outbreaks. All stakeholders are encouraged to address the challenges and collaborate to promote the safe and evidence-based use of telemedicine during the current pandemic and future outbreaks. For countries without integrated telemedicine in their national health care system, the COVID-19 pandemic is a call to adopt the necessary regulatory frameworks for supporting wide adoption of telemedicine.

AbstractIn immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three- to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from <7.5 (IQR : <7.5−15.1) to 47.1 (IQR <7.5−284.2). Collectively, our data indicate that a fourth dose of the mRNA-1273 vaccine in kidney transplant recipients with a weak antibody response after three previous doses improves serum neutralization against the delta variant.

International audience; Background and objectives Dialysis patients have a high mortality risk after coronavirus disease 2019 (COVID-19) and an altered immunologic response to vaccines, but vaccine clinical effectiveness remains unknown in this population. Design, setting, participants, & measurements Using Bayesian multivariable spatiotemporal models, we estimated the association between vaccine exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severe infections (with hospital admission) in dialysis patients from simultaneous incidence in the general population. For dialysis patients, cases were reported within the French end-stage kidney disease REIN registry from March 11, 2020, to April 29, 2021, and vaccine exposure (first dose) was reported in weekly national surveys since January 2021. Cases in the general population were obtained from the national exhaustive inpatient surveillance system (SI-VIC database), and vaccination coverage (first dose) was obtained from the national surveillance system (VAC-SI database). Results During the first wave, incidence in dialysis patients was approximately proportional to the general population. However, we showed a lower relative incidence for dialysis patients during the second wave (compared with that observed in nondialysis patients), suggesting an effect of prevention measures. Moreover, from the beginning of the vaccination rollout, incidence in dialysis patients was lower compared with predictions based on the first and second waves. Adding vaccination coverages in dialysis and nondialysis patients as predictors allowed the reported cases to be fit correctly (3685 predicted cases, 95% confidence interval, 3552 to 3816, versus 3620 reported). Incidence rate ratios were 0.37 (95% confidence interval, 0.18 to 0.71) for vaccine exposure in dialysis patients and 0.50 (95% confidence interval, 0.40 to 0.61) per 10% higher in vaccination coverage in the same-age general population, meaning that vaccine exposure in dialysis patients and the general population was independently associated with lower hospitalization rate of dialysis patients. Conclusions Our findings suggest that vaccination may yield a protective effect against severe forms of COVID-19 in dialysis patients, despite altered immunologic vaccine responses.

Emerging epidemics and local infection clusters are initially prone to stochastic effects that can substantially impact the epidemic trajectory. While numerous studies are devoted to the deterministic regime of an established epidemic, mathematical descriptions of the initial phase of epidemic growth are comparatively rarer. Here, we review existing mathematical results on the epidemic size over time, and derive new results to elucidate the early dynamics of an infection cluster started by a single infected individual. We show that the initial growth of epidemics that eventually take off is accelerated by stochasticity. These results are critical to improve early cluster detection and control. As an application, we compute the distribution of the first detection time of an infected individual in an infection cluster depending on the testing effort, and estimate that the SARS-CoV-2 variant of concern Alpha detected in September 2020 first appeared in the United Kingdom early August 2020. We also compute a minimal testing frequency to detect clusters before they exceed a given threshold size. These results improve our theoretical understanding of early epidemics and will be useful for the study and control of local infectious disease clusters. revised version

Abstract Background The ongoing COVID-19 pandemic has disrupted the surgical training of residents. There is a real concern that trainees will not be able to meet their training requirements. Low-fidelity surgical simulation appears to be an alternative for surgical training. The educational benefits of repeating ossiculoplasty simulations under a microscope have never been evaluated. With this study we aimed to evaluate the differences in performance scores and on a global rating scale before and after training on an ossiculoplasty simulator. Methods In this quasi-experimental, prospective, single-centre, before-after study with blinded rater evaluation, residents performed five microscopic ossiculoplasty tasks with a difficulty gradient (sliding beads onto rods, the insertion of a partial prosthesis, the insertion of a total prosthesis, and the insertion of a stapedotomy piston under microscopic or endoscopic surgery) before and after training on the same simulator. Performance scores were defined for each task, and total performance scores (score/min) were calculated. All data were collected prospectively. Results Six out of seven intermediate residents and 8/9 novices strongly agreed that the simulator was an effective training device and should be included in the ENT residency program. The mean effect of training was a significant increase in the total performance score (+ 0.52 points/min, [95 % CI, 0.40–0.64], p < 0.001), without a significant difference between novice and intermediate residents. Conclusions This preliminary study shows that techniques for middle-ear surgery can be acquired using a simulator, avoiding any risk for patients, even under lockdown measures.

SummaryState-of-the-art methods for single-cell RNA sequencing (scRNA-seq) Differential Expression Analysis (DEA) often rely on strong distributional assumptions that are difficult to verify in practice. Furthermore, while the increasing complexity of clinical and biological single-cell studies calls for greater tool versatility, the majority of existing methods only tackle the comparison between two conditions. We propose a novel, distribution-free, and flexible approach to DEA for single-cell RNA-seq data. This new method, called ccdf, tests the association of each gene expression with one or many variables of interest (that can be either continuous or discrete), while potentially adjusting for additional covariates. To test such complex hypotheses, ccdf uses a conditional independence test relying on the conditional cumulative distribution function, estimated through multiple regressions. We provide the asymptotic distribution of the ccdf test statistic as well as a permutation test (when the number of observed cells is not sufficiently large). ccdf substantially expands the possibilities for scRNA-seq DEA studies: it obtains good statistical performance in various simulation scenarios considering complex experimental designs (i.e. beyond the two condition comparison), while retaining competitive performance with state-of-the-art methods in a two-condition benchmark. We apply ccdf to a large publicly available scRNA-seq dataset of 84,140 SARS-CoV-2 reactive CD8+ T cells, in order to identify the diffentially expressed genes across 3 groups of COVID-19 severity (mild, hospitalized, and ICU) while accounting for seven different cellular subpopulations.

AbstractWe leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.