Transient anti-interferon autoantibodies in the airways are associated with efficient recovery from COVID-19 (preprint)

Pre-existing anti-interferon alpha (anti-IFN-) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN- autoantibodies in the airways - the initial site of infection - can also determine disease outcomes. In this study, we developed a new multiparameter technology, flowBEAT, to quantify and profile the isotypes of anti-IFN- and anti-SARS-CoV-2 antibodies in longitudinal samples collected over 20 months from the airway and matching blood of 129 donors with mild, moderate, and severe COVID-19. We found unexpectedly that nasal anti-IFN- autoantibodies were induced post-infection onset in more than 70% of mild to moderate COVID-19 cases and associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN- autoantibodies followed the peak of host IFN- production and waned with disease recovery, revealing a regulated balance between IFN- and anti-IFN- response. Notably, only a subset of mild to moderate patients progressed to develop systemic anti-IFN-, which correlated with systemic inflammation and worsened symptoms. In contrast, patients with life-threatening COVID-19 sustained elevated anti-IFN- in both airways and blood, coupled with uncontrolled viral load and IFN- production. Our studies thereby reveal a novel protective role for nasal anti-IFN- autoantibodies in the immunopathology of COVID-19 and, more broadly, suggest that anti-IFN- may serve an important regulatory function to restore homeostasis following viral invasion of the respiratory mucosa.

Convergent Sequence Features of Antiviral B Cells (preprint)

Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, building diverse antigen-specific antibody repertoires. In recent years, these repertoires have become an important source for novel antibody-based antiviral therapeutics, yet there is still limited understanding of the determinants of antibody-antigen specificity. Here, we generated a large dataset mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against twenty viral antigens representing diverse pathogens of biomedical significance. Analysis revealed antigen-specific patterns in variable gene usage, gene pairing, and somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals. These results help define the characteristics of human antibody repertoires simultaneously against an unprecedented number and diversity of viral targets. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.

Comprehensive Code List Associated with CDC-Defined High-Risk Underlying Medical Conditions Leading to Potential Progression to Severe COVID-19 Outcomes

Objectives: This analysis was conducted to develop a comprehensive list of ICD-10 CM codes for underlying conditions identified by the CDC as being associated with high-risk of developing severe COVID-19 and assessed the consistency of these codes when applied to large US based datasets. Method(s): The comprehensive list of ICD 10-CM codes for CDC-defined high-risk underlying conditions were mapped from CDC references and FDA Sentinel code lists. These codes were subsequently applied to Optum's de-identified Clinformatics Data Mart Database (claims) and the Optum de-identified Electronic Health Record (EHR) database across 3 years (2018, 2019 and 2020) among continuously enrolled subjects >= 12 years of age to determine the performance and consistency in identifying these high-risk underlying conditions annually over these years. Result(s): A total of 10,276 ICD-10 codes were mapped to 21 underlying conditions. Within the claims data, 62.7% of subjects >= 12 years had >= 1 CDC-defined high-risk condition (excluding age) with 26.6% of patients >= 65 years while in the EHR data 38% had >= 1 high-risk underlying condition (excluding age) with 14.4% >= 65 years. These results were similar and consistent in both datasets across all years. Patients aged 12-64 years in the claims data had a higher rate of >=1 high risk underlying condition relative to the EHR data, 49.3% and 34%, respectively. The top 5 conditions among the >= 65 were identical across both databases: hypertension, immunocompromised status, heart conditions, diabetes (type 1 or 2), and overweight/obesity. The top 5 conditions among the 12-64 age group were also similar among the databases and included: immunocompromised status, hypertension, overweight/obesity, smoking (current or former), and mental health conditions. Conclusion(s): These findings present a comprehensive list of codes that can be used by researchers, clinicians and policy makers to identify and characterize patients that may be at high-risk for severe COVID-19 outcomes.Copyright © 2023

Uptake of the Post COVID-19 Condition ICD-10-CM Diagnosis Code By Social Factors

Objectives: Post-COVID conditions (PCC) are increasingly reported in people who had COVID. Certain racial or socioeconomic groups may be at greater risk for PCC and less likely to seek care. We examined the uptake of the new ICD-10-CM diagnosis code for PCC in routine clinical practice in the United States and how it varied by race and payer group. Method(s): Using the Optum de-identified Electronic Health Record (EHR) dataset, we identified patients with an ICD-10-CM code for PCC (U09.9) between October 1, 2021, through March 31, 2022, with 6 months of prior EHR activity. The earliest diagnosis defined the index date. All concurrent diagnoses were measured on the index date. Prior COVID diagnosis was assessed using all available data before the index date. Result(s): There were 23,647 patients: 9.9% were African American, 12.1% had Medicaid, and 2.4% were uninsured. There was an overrepresentation of white patients among those with PCC (78.6% compared with 69.6% of the overall EHR in 2021). More African American (24.1%), Medicaid (23.1%), and uninsured (27.5%) patients were diagnosed in the inpatient setting or emergency department than whites (14.0%) and commercially insured patients (10.0%). Among racial groups, African Americans had the highest percentage of documented prior COVID diagnosis at 63.6%. Of concurrent diagnoses, shortness of breath and acute respiratory failure with hypoxia were higher among African Americans (13.9% and 6.1%, respectively) than whites (11.5% and 4.3%, respectively). The same pattern was seen when comparing Medicaid and uninsured to commercial payors. Conclusion(s): The PCC code was used differently across racial groups and payor types and captures varying manifestations of PCC. The differences in diagnosis locations underscore the importance of using data capturing all care settings when conducting studies using this code. Subgroup analyses are important for future studies using U09.9 due to variability in code application.Copyright © 2023

Immunotherapy: ADOPTIVE T CELL IMMUNOTHERAPY FOR SARS-COV-2

Background & Aim: Despite the successful implementation of vaccines worldwide, COVID-19 remains a risk in patients with a compromised immune system. Emerging viral variants have also reduced the effectiveness of monoclonal antibody therapies in these patients. New treatment options are therefore required to improve clinical outcomes. Methods, Results & Conclusion(s): T cell immunotherapy has proven effective for the treatment of a number of refractory viral diseases in patients with a compromised immune system. We have now completed the manufacture of a bank of SARS-CoV-2 specific T cells and commenced an open-label phase I clinical trial at the Royal Brisbane and Women's Hospital, Australia. Patients enrolled in the study receive two doses of partially HLA-matched allogeneic T cells at a fortnightly interval. We have thus far recruited and treated three immune compromised patients with SARS-CoV-2 T cells. In two of the three patients treated thus far, the administration of T cell therapy was coincident with the clearance of viral load after 28 days. Viral clearance in these patients was also associated with an increase in circulating SARS-CoV-2 specific T cells. Our preliminary observations suggest that SARS-CoV-2 specific T cell therapy is well tolerated and has the potential to impact viral control in immune compromised patients.Copyright © 2023 International Society for Cell & Gene Therapy

Changes in anticoagulant and antiplatelet drug supply at US hospitals before and during the COVID-19 pandemic (2018-2021).

PURPOSE: Antithrombotic agents have a role in coronavirus disease 2019 (COVID-19) treatment, but the pandemic disrupted medication supply. This study examined changes in the volume of oral and parenteral anticoagulant and antiplatelet medications at US hospitals during the pandemic. METHODS: IQVIA National Sales Perspective (NSP) data was used to determine the monthly volume of anticoagulants and antiplatelets purchased at US hospitals between January 2018 and February 2021. Mean monthly medication volumes, reported as extended units (EUs), and year-over-year changes in medication volume were determined. A single-group interrupted time series analysis was used to evaluate changes in the rate of growth of monthly medication volumes before (January 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. RESULTS: Overall, there was a 43.4% decline in the total volume of anticoagulants and antiplatelets at US hospitals in March 2020, driven by a decrease in heparin volume. Mean monthly volumes decreased significantly (P < 0.05) for parenteral anticoagulants (-106,691,340 EU [95% CI, -200,033,910 to -13,348,780]), oral anticoagulants (-354,800 EU [95% CI, -612,180 to -97,420]), and parenteral antiplatelets (-391,880 EU [95% CI, -535,420 to -248,330]). During the pandemic, the monthly volume of oral anticoagulants, parenteral anticoagulants, and parenteral antiplatelets grew significantly more than in the prepandemic period. This growth was primarily seen in volumes of apixaban, argatroban, enoxaparin, heparin, eptifibatide, and tirofiban. Apixaban and heparin volumes continued a prepandemic uptrend, while argatroban and eptifibatide volumes reversed trend. CONCLUSION: Rapid changes in anticoagulant and antiplatelet volume at US hospitals during the COVID-19 pandemic highlight the need for institutional protocols to manage fluctuating medication volume demands.

A culturally tailored personaliseD nutrition intErvention in South ASIan women at risk of Gestational Diabetes Mellitus (DESI-GDM): a randomised controlled trial protocol.

INTRODUCTION: South Asians are more likely to develop gestational diabetes mellitus (GDM) than white Europeans. Diet and lifestyle modifications may prevent GDM and reduce undesirable outcomes in both the mother and offspring. Our study seeks to evaluate the effectiveness and participant acceptability of a culturally tailored, personalised nutrition intervention on the glucose area under the curve (AUC) after a 2-hour 75 g oral glucose tolerance test (OGTT) in pregnant women of South Asian ancestry with GDM risk factors. METHODS AND ANALYSIS: A total of 190 South Asian pregnant women with at least 2 of the following GDM risk factors-prepregnancy body mass index>23, age>29, poor-quality diet, family history of type 2 diabetes in a first-degree relative or GDM in a previous pregnancy will be enrolled during gestational weeks 12-18, and randomly assigned in a 1:1 ratio to: (1) usual care, plus weekly text messages to encourage walking and paper handouts or (2) a personalised nutrition plan developed and delivered by a culturally congruent dietitian and health coach; and FitBit to track steps. The intervention lasts 6-16 weeks, depending on week of recruitment. The primary outcome is the glucose AUC from a three-sample 75 g OGTT 24-28 weeks' gestation. The secondary outcome is GDM diagnosis, based on Born-in-Bradford criteria (fasting glucose>5.2 mmol/L or 2 hours post load>7.2 mmol/L). ETHICS AND DISSEMINATION: The study has been approved by the Hamilton Integrated Research Ethics Board (HiREB #10942). Findings will be disseminated among academics and policy-makers through scientific publications along with community-orientated strategies. TRIAL REGISTRATION NUMBER: NCT03607799.

A Quality Improvement Innovation for Reproductive Health Planning in the Time of COVID.

OBJECTIVES: To see if an outreach approach with telehealth is feasible and acceptable to patients to talk about their reproductive health; and as a secondary outcome, capture data on time spent on the visit and what kind of information was discussed. METHODS: A registry was created from three family physicians' panels of all adult patients with anticipated ability to become pregnant ages 18-45 who had not had a documented reproductive health discussion in the previous 6 months. Using that registry, outreach was performed to schedule a telehealth visit to discuss their reproductive health with their primary care provider. The visit was standardized using the One Key Question approach. For patients who agreed to participate in the research, the patient completed a survey about their experience. The provider also completed a survey on the time spent and the issues addressed. RESULTS: Two hundred and six patients were called. Ninety patients (44%) could not be reached. Of the remaining patients, 34 scheduled either a telehealth or in-person visit and 7 also agreed to participate in the survey. New information was uncovered in the visit in 86% of participants. The most common need uncovered during the visit was unrelated medical needs (71%), followed by preconception health education/advice (43%) and contraception needs/counseling (29%). Most participants found the telehealth visit valuable. CONCLUSIONS: An outreach methodology can uncover unmet health needs, both reproductive and otherwise. We found that people who had the visit often needed something, but a majority of patients declined the visit saying that they did not think they needed it. It is possible that patients are not aware of the value of reproductive health discussions, and therefore clinicians need to take every opportunity to have these discussions whenever possible, whether through outreach or inreach (during already scheduled visits).

Lessons learned from the experiences and perspectives of frontline healthcare workers on the COVID-19 response (preprint)

Background During the COVID-19 pandemic, healthcare systems and healthcare workers (HCWs) faced significant demands and unique challenges. In this qualitative study, we explore the effects of the COVID-19 public health policies on British Columbia’s frontline HCWs, describe what worked in the management of the pandemic, and elucidate the lessons learned that could be applied to future pandemic preparedness, recovery and response.Methods This qualitative descriptive study is part of a larger, national multi-case study on pandemic policy communication and uptake. Semi-structured interviews were conducted from November 2020- June 2021 with fourteen HCWs working in long-term care (LTC), acute care and public health settings. Data were inductively coded, and analyzed following a resilience framework for public health emergency preparedness, which emphasizes the essential elements of a public health system, vital to all phases of health emergency management, readiness, response and recovery.Results HCWs experienced confusion, frustration, uncertainty, anxiety, fatigue and stress, during the pandemic and detailed challenges that affected policy implementation. This included communication and coordination inconsistencies between the province and regional health authorities; lack of involvement of frontline staff in pandemic planning; inadequate training and support; inadequate personal protective equipment resource capacity and mobilization; and staffing shortages. HCWs recommended increased collaboration between frontline staff and policy makers, investment in preparing and practicing pandemic plans, and the need for training in emergency management and infection prevention and control.Conclusions Pandemic planning, response and recovery should include inputs from actors/key stakeholders at the provincial, regional and local levels, to facilitate better coordination, communication and outcomes. Also, given the critical roles of frontline HCWs in policy implementation, they should be adequately supported and consideration must be given to how they interpret and act on policies. Bi-directional communication channels should be incorporated between policymakers and frontline HCWs to verify the appropriate adoption of policies, reflective learning, and to ensure policy limitations are being communicated and acted upon by policy makers.

The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3' UTR of wild-type and s2m deletion viruses using selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) and dimethyl sulfate mutational profiling and sequencing (DMS-MaPseq). These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3'-UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2. IMPORTANCE RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contain functional structures to support virus replication, translation, and evasion of the host antiviral immune response. The 3' untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is an RNA structural element that is found in many RNA viruses. This motif was discovered over 25 years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also observed no impact of the deletion on other known RNA structures in the same region of the genome. These experiments demonstrate that s2m is dispensable for SARS-CoV-2.

The Rapid Evolution of Crisis Mental Health Services in Utah: Opportunities and Challenges as a Result of the Global Pandemic.

Our country is facing a resurgence of behavioral health crises from over the past 30 years, further illuminated and exacerbated by the global COVID-19 pandemic. Increasing suicide crises among youths over recent decades, untreated anxiety and depression, and serious mental illness are signs of the need for improvements in accessible, affordable, timely, and comprehensive behavioral health services. Against the backdrop of high suicide rates and low behavioral health services in Utah, statewide collaborators aligned with a common goal: deliver crisis services to anyone, anytime, and anywhere. After its initiation in 2011, the integrated behavioral health crisis response system continued to expand and excel, ultimately improving access and referral to services, flattening suicide rates, and reducing stigma. The global pandemic further motivated the expansion of Utah's crisis response system. This review focuses on the unique experiences of the Huntsman Mental Health Institute as a catalyst and partner in these changes. Our goals are to: inform about unique Utah partnerships and actions in the crisis mental health space, describe initial steps and outcomes, highlight continuing challenges, discuss pandemic-specific barriers and opportunities, and explore the long-term vision to improve quality and access to mental health resources.

Genomic surveillance identifies potential risk factors for SARS-CoV-2 transmission at a mid-sized university in a small rural town.

Understanding transmission dynamics of SARS-CoV-2 in institutions of higher education (IHEs) is important because these settings have potential for rapid viral spread. Here, we used genomic surveillance to retrospectively investigate transmission dynamics throughout the 2020-2021 academic year for the University of Idaho ("University"), a mid-sized IHE in a small rural town. We generated genome assemblies for 1168 SARS-CoV-2 samples collected during the academic year, representing 46.8% of positive samples collected from the University population and 49.8% of positive samples collected from the surrounding community ("Community") at the local hospital during this time. Transmission dynamics differed for the University when compared to the Community, with more infection waves that lasted shorter lengths of time, potentially resulting from high-transmission congregate settings along with mitigation efforts implemented by the University to combat outbreaks. We found evidence for low transmission rates between the University and Community, with approximately 8% of transmissions into the Community originating from the University, and approximately 6% of transmissions into the University originating from the Community. Potential transmission risk factors identified for the University included congregate settings such as sorority and fraternity events and residences, holiday travel, and high caseloads in the surrounding community. Knowledge of these risk factors can help the University and other IHEs develop effective mitigation measures for SARS-CoV-2 and similar pathogens.

Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination: estimation and correction using a data augmentation model (preprint)

Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and [≥]70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iterative data augmentation. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.

Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands, January 6, 2021 through August 30, 2022.

BACKGROUND: Vaccines against COVID-19 have proven effective in preventing COVID-19 hospitalisation. In this study, we aimed to quantify part of the public health impact of COVID-19 vaccination by estimating the number of averted hospitalisations. We present results from the beginning of the vaccination campaign ('entire period', January 6, 2021) and a subperiod starting at August 2, 2021 ('subperiod') when all adults had the opportunity to complete their primary series, both until August 30, 2022. METHODS: Using calendar-time specific vaccine effectiveness (VE) estimates and vaccine coverage (VC) by round (primary series, first booster and second booster) and the observed number of COVID-19 associated hospitalisations, we estimated the number of averted hospitalisations per age group for the two study periods. From January 25, 2022, when registration of the indication of hospitalisation started, hospitalisations not causally related to COVID-19 were excluded. RESULTS: In the entire period, an estimated 98,170 (95 % confidence interval (CI) 96,123-99,928) hospitalisations were averted, of which 90,753 (95 % CI 88,790-92,531) were in the subperiod, representing 57.0 % and 67.9 % of all estimated hospital admissions. Estimated averted hospitalisations were lowest for 12-49-year-olds and highest for 70-79-year-olds. More admissions were averted in the Delta period (72.3 %) than in the Omicron period (63.4 %). CONCLUSION: COVID-19 vaccination prevented a large number of hospitalisations. Although the counterfactual of having had no vaccinations while maintaining the same public health measures is unrealistic, these findings underline the public health importance of the vaccination campaign to policy makers and the public.

The association of maternal sugary beverage consumption during pregnancy and the early years with childhood sugary beverage consumption.

OBJECTIVES: A woman's food choices during pregnancy may be associated with her offspring's food choices. Several studies support an association between childhood sugary beverage (SB) consumption and poor cardiometabolic health. This study aimed to assess the association of maternal SB consumption during pregnancy and later, with her offspring's SB consumption in early infancy and childhood. METHODS: A total of 1945 women and 1595 children participating in 3 Canadian studies reported SB consumption during pregnancy, at 2 years of age, and/or at school age (5 to 8 years old). Mother and offspring SB intakes were self-reported by mothers. Multivariable linear regression analyses were conducted within each cohort and cohort data were combined using fixed effect meta-analyses. RESULTS: Maternal SB consumption during pregnancy was associated with higher offspring SB consumption at 2 years of age (standardized ß = 0.19 predicted change in the number of standard deviations of offspring SB intake for an increase of 1 standard deviation in maternal serving [95% CI: 0.16 to 0.22]). Concurrent maternal SB consumption was associated with higher offspring SB intake when children were aged 5 to 8 years (standardized ß= 0.25 [95% CI: 0.10 to 0.40]). CONCLUSION: Maternal SB consumption during pregnancy is associated with a marginally higher SB intake among their offspring at age 2, and concurrent maternal consumption is associated with a higher SB intake among school-aged offspring (5 to 8 years old). Future interventions tailored for pregnancy and early childrearing years to reduce SB intakes of mothers may reduce young children's SB intake.

RéSUMé: OBJECTIFS: Il peut y avoir un lien entre les choix alimentaires d'une femme pendant la grossesse et ceux de son enfant. Plusieurs études font état d'une association entre la consommation de boissons sucrées (BS) durant l'enfance et la mauvaise santé cardiométabolique. Notre étude visait à évaluer l'association entre la consommation de BS des mères pendant et après la grossesse et la consommation de BS de leurs enfants durant la petite enfance et l'enfance. MéTHODE: En tout, 1 945 femmes et 1 595 enfants participant à 3 études canadiennes ont fait état de leur consommation de BS pendant la grossesse, à l'âge de 2 ans et/ou à l'âge scolaire (5 à 8 ans). La consommation de BS des mères et des enfants a été déclarée par les mères. Des analyses de régression linéaire multivariée ont été menées dans chaque cohorte, et les données des cohortes ont été combinées à l'aide de méta-analyses à effets fixes. RéSULTATS: La consommation maternelle de BS pendant la grossesse était associée à une consommation de BS plus élevée chez les enfants à l'âge de 2 ans (le coefficient ß standardisé = 0,19 prédisait le changement du nombre d'écart-types de consommation de BS chez les enfants pour chaque hausse de 1 écart-type de la portion maternelle [IC de 95 % : 0,16 à 0,22]). La consommation maternelle concomitante de BS était associée à une consommation de BS plus élevée chez les enfants lorsqu'ils étaient âgés de 5 à 8 ans (coefficient ß standardisé = 0,25 [IC de 95 % : 0,10 à 0,40]). CONCLUSION: La consommation maternelle de BS pendant la grossesse est associée à une consommation de BS marginalement plus élevée chez l'enfant à l'âge de 2 ans, et la consommation maternelle concomitante est associée à une consommation de BS plus élevée chez l'enfant d'âge scolaire (5 à 8 ans). De futures interventions visant à réduire la consommation de BS des mères pendant la grossesse et durant les premières années où elles élèvent leurs enfants pourraient réduire la consommation de BS des jeunes enfants.

Tracking the prevalence and emergence of SARS CoV2 variants of concern using a regional genomic surveillance program (preprint)

SARS-CoV-2 molecular testing coupled with whole genome sequencing is instrumental for real-time genomic surveillance. Genomic surveillance is critical for monitoring the spread of variants of concern (VOC) as well as novel variant discovery. Since the beginning of the pandemic millions of SARS-CoV-2 genomes have been deposited into public sequence databases. This is the result of efforts of both national and regional diagnostic laboratories. Here we describe the results of SARS-CoV-2 genomic surveillance from February 2021 to June 2022 at a metropolitan hospital in the USA. We demonstrate that consistent daily sampling is sufficient to track the regional prevalence and emergence of VOC. Similar sampling efforts should be considered a viable option for local SARS-CoV-2 genomic surveillance at other regional laboratories.

Hesitant adopters: COVID-19 vaccine hesitancy among diverse vaccinated adults in the United States

Background: Despite the United States (US) having an abundant supply of COVID-19 vaccines, vaccination rates lag behind other high-income countries, suggesting that vaccine hesitancy and attitudes play a greater role in public health measures than pure supply and access. With the acknowledgment that vaccination attitudes and status may or may not be correlated, this study examined COVID-19 vaccine hesitancy among vaccinated US adults by asking: 1) What is the prevalence of COVID-19 vaccine hesitancy among the vaccinated? 2) Does COVID-19 vaccine hesitancy vary across sociodemographic characteristics? 3) Does COVID-19 vaccine hesitancy vary by healthcare access and influenza vaccination over the past 5 years? Methods: Data were collected through an online survey of 2022 US adults with a final analytic sample of 1383 vaccinated respondents. Results: Overall, 48.8% of vaccinated adults reported some level of hesitancy, while a slight majority reported they were "not at all hesitant”. Younger respondents, women, and Black and American Indian or Alaska Native participants had greater adjusted odds of being more hesitant towards receiving the COVID-19 vaccine. Respondents who had a primary care physician had greater adjusted odds than those who did not have a primary care physician of being more hesitant towards receiving the COVID-19 vaccine. Conclusions: This is the first population-based national sample study examining COVID-19 vaccine hesitancy among vaccinated individuals from subgroups of distinctive backgrounds in order to inform targeted strategies for reducing vaccine hesitancy. Findings can assist in efforts to increase vaccination rates and also decrease vaccine hesitancy at the national level. © 2023 The Author(s)

Telerehabilitation versus face-to-face rehabilitation in the management of musculoskeletal conditions: a systematic review and meta-analysis

Background: Musculoskeletal conditions such as spinal pain and osteoarthritis are among the leading causes of years lived with disability worldwide. With the COVID-19 pandemic forcing many healthcare providers to change the way in which care for chronic conditions is delivered, telehealth is an alternative to face-to-face consultations that can be used for both assessment and provision of therapy and support. Objectives: To identify, appraise and synthesise findings from all randomised controlled trials (RCTs) that compared telehealth to face-to-face consultations for patients with any type of musculoskeletal condition. Methods: Systematic review and meta-analysis. We used the GRADE approach to assess the quality of evidence related to all outcomes. We searched three electronic databases (PubMed, Embase, CENTRAL), clinical trial registries and citing-cited references of included studies. Results: Five RCTs were includable: one in patients with osteoarthritis of the knee, one in patients with osteoarthritis of the knee or hip in preparation for a total joint arthroscopy and three after total knee replacement. Telehealth was conducted by video in four trials and by phone in one. A total of 402 participants were analysed across the five trials. There were no significant differences in pain outcomes (WOMAC) between telehealth and face-to-face therapy immediate post-intervention (mean difference (MD): 0.12 (95% CI −2.3 to 2.6, p =.92) or two months post-intervention (MD): 1.2, (95% CI: −2.7 to 5.1, p =.55). Similarly, outcomes related to function, quality of life and satisfaction were comparable between the two modes of delivery immediate post-intervention, with no significant differences reported. Conclusion: There is limited low quality evidence that there is no significant differences between telehealth-based delivery of rehabilitation to patients with osteoarthritis or following knee surgery and face-to-face therapy for pain, function, quality of life and satisfaction. These findings should be should be interpreted with caution due to the small number of included studies and small sample size. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M.

Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the ß-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.