NILMATREVIR-RITONAVIR TREATMENT IN CHILDREN WITH SARS-CoV-2 INFECTION

Background: Children seem to experience a less severe form of COVID-19 disease than adults, nevertheless, cases of severe infection have been described in a small proportion of patients, requiring hospitalization in 5-10% of cases. Among COVID-19 deaths 0,4% occurred in children and adolescents under 20 years of age. Most hospitalized children with acute COVID-19 had underlying conditions. Moreover, some children with previous COVID-19 infection, may later develop Multisystem Inflammatory Syndrome in Children (MIS-C), a rare but serious condition associated with COVID-19. These data suggest that a specific therapy is necessary in high-risk pediatric population, in order to prevent severe COVID-19, especially in children with underlying conditions. Antiviral paediatric data are currently very few Methods: We conducted a retrospective study on patients < 18 years of age who received Paxlovid (nirmatrelvir-ritonavir) for the treatment of mild-tomoderate COVID-19 at Bambino Gesu Children's Hospital from April 2022 to September 2022. Patients at high risk of progression to severe COVID-19 who had no need of supplemental oxygen received Paxlovid according to AIFA's indications for adults with the Informed Consent of relatives Results: 40 patients aged 1-18 years with confirmed SARS-CoV-2 infection were treated with Paxlovid (Tab 1)The average symptom duration was 4.2 days. No patient developed severe COVID-19 r All patients were treated within 5 days of symptom onset, Four patients received a longer course treatment (10 days) due to the persistence of symptoms combined with the presence of severe comorbidities .The mean time of viral shedding was 12.7 days, with a patient being persistently positive for 56 days. After Paxlovid initiation, only 5 patients (12.5%) experienced adverse reactions: Conclusion(s): Treatment with Paxlovid has proven to be safe. Further pharmacokinetic studies are required species for children < 5 years old.

The Pandemic and the Regions. The distribution of competences to the test of the health emergency

The contribution aims to highlight the effects of the pandemic on the distribution of competences between the State and the Regions. Having established the attributes of relevance for the management of the health emergency that the Constitution assigns to state and regional legislators, the analysis will focus on the legal instruments used to manage the Covid-19 pandemic in its various phases and on the relationship between central and regional regulatory acts, with particular regard to the principle of loyal collaboration. Subsequently, attention will be focused on the attempts, implemented in particular by the Valle d'Aosta Region and the Autonomous Province of Bolzano, to manage the pandemic through an autonomous route, and on the consequences of the Constitutional Court's sentence no. 37/2021. Finally, the contribution will question the future of the division of competences in the pandemic-sanitary sphere. © 2023, Societa Editoriale Federalismi s.r.l. All rights reserved.

COVID-19 Vaccines and Thromboembolic Events with Thrombocytopenia: Data from Italian Pharmacovigilance Public Database

Introduction: During large-scale vaccination campaign against COVID-19, the Italian Medicines Agency (AIFA) in collaboration with the Regional Centres of Pharmacovigilance have carried out a closely monitoring of Individual Case Safety Reports (ICSRs) about Adverse Event Following Immunisation (AEFIs) related to COVID- 19 vaccines and have assured a constant communication through public monthly reports1. During the first months of the vaccination campaign, a signal of rare events of thrombosis associated with thrombocytopenia2, particularly in young women, was detected by health authorities associated with the viral vector vaccines ChAdOx1- S and Ad26.COV2-S. Objective(s): To present a comprehensive assessment of thrombotic and thromboembolic events associated with thrombocytopenia following COVID-19 immunisation with viral vector vaccines recorded in the Italian National Pharmacovigilance Network database Methods: We selected all ICSRs reported from 27 December 2020 to 26 December 2021 containing Preferred Terms (PT) related to platelet count reduction associated with PT related to thrombotic and thromboembolic events (clinical symptoms and/or diagnostic tests). All cases of thrombotic and thromboembolic events reporting thrombocytopenia in the narrative description of the report were also reviewed. The selected ICRSs were submitted to the independent evaluation of three pharmacovigilance experts who blindly classified into 5 levels of diagnostic certainty, according to the definition provided by the Brighton Collaboration Group (BCG)3. Disagreement were resolved by plenary discussion. Result(s): 12,166,236 doses of ChAdOx1-S and 1,500,746 of Ad26.COV2-S have been administered in Italy during the considered interval with overall 23,358/117,947 ICSRs related to ChAdOx1-S (19.8 %) and 1,580/117,947 related to Ad26.COV2-S (1.3 %). A total of 134 reports after vaccination with adenoviral vaccines were identified according to the inclusion criteria, of which 107 cases were defined as thrombotic thrombocytopenia (95 following ChAdOx1-S and 12 after Ad26.COV2-S). 27 reports were defined as ''not case'' (level 5, Brighton) on the basis of clinical examination or investigation, or because of the presence of heparin as a concomitant drug. Furthermore, 3 reports were excluded because of a hereditary thrombophilia or a previous history of other thrombotic episodes. Seventy-seven cases were classifiable as BCG levels 1, 2, and 3 (definite, probable and possible cases, respectively) with an overall reporting rate at about 1 case per approximately 200,000 doses administered. Women aged 30 to 49 years showed the highest reporting rates. Conclusion(s): In Italy, the rates of thrombotic thrombocytopenia following COVID-19 immunisation with viral vector vaccines are in line with those reported in other Countries.

[Clinical, functional and tomographic respiratory sequels of patients hospitalized for COVID-19 at six month of diagnosis: SECUELAR-19 trial]

INTRODUCTION: There is scarce information about middle-term evolution of hospitalized patients who suffer from pneumonia caused by COVID-19. The objective of this study is to determine the clinical, respiratory, tomographic and functional impact on COVID-19 patients with moderate (MP) to severe (SP) pneumonia after six months of acute infection. METHODS: Analysis was carried out by MP and SP groups, desaturators during the 6-minute-walking test and the presence of fibrotic like pattern on HRCT. Outcomes at 3 and 6 months were compared. RESULTS: The analysis included 129 patients, between 57 ± 11 years old. Frequent comorbidities were: arterial hypertension 38.1%, diabetes 30.4%, respiratory 18.6%). Comparing 3 and 6 months, improvement in quality of life was observed in MP and SP. The DP walked less meters in the MWT, worsened life quality and more fibrotic like pattern. The fibrotic pattern was related to the fall of CVF < 80% on MP and SP (p = 0.048 and p = 0.007), and with DP (p = 0.002). On multivariated analysis, the fibrotic like pattern was associated to the reduction of CVF with OR = 4.44 (1.94-10.18, p <0.01) and desaturation OR = 5.01(1.63-15.42, p < 0.01). On this cohort it was observed more functional and tomographic compromise on the DP The fibrotic like pattern was related to worse functional evolution and oximetry. DISCUSSION: Follow-up after discharge of COVID-19 patients with SP, DP or fibrotic changes in HCRT is underlined.

COVID-19 Vaccines and Thromboembolic Events with Thrombocytopenia: Data from Italian Pharmacovigilance Public Database: An International Journal of Medical Toxicology and Drug Experience

Introduction: During large-scale vaccination campaign against COVID-19, the Italian Medicines Agency (AIFA) in collaboration with the Regional Centres of Pharmacovigilance have carried out a closely monitoring of Individual Case Safety Reports (ICSRs) about Adverse Event Following Immunisation (AEFIs) related to COVID19 vaccines and have assured a constant communication through public monthly reports1. During the first months of the vaccination campaign, a signal of rare events of thrombosis associated with thrombocytopenia2, particularly in young women, was detected by health authorities associated with the viral vector vaccines ChAdOx1S S Ad26.COV2-S. Objective: To present a comprehensive assessment of thrombotic and thromboembolic events associated with thrombocytopenia following COVID-19 immunisation with viral vector vaccines recorded in the Italian National Pharmacovigilance Network database Methods: We selected all ICSRs reported from 27 December 2020 to 26 December 2021 containing Preferred Terms (PT) related to platelet count reduction associated with PT related to thrombotic and thromboembolic events (clinical symptoms and/or diagnostic tests). All cases of thrombotic and thromboembolic events reporting thrombocytopenia in the narrative description of the report were also reviewed. The selected ICRSs were submitted to the independent evaluation of three pharmacovigilance experts who blindly classified into 5 levels of diagnostic certainty, according to the definition provided by the Brighton Collaboration Group (BCG)3. Disagreement were resolved by plenary discussion. Results: 12,166,236 doses of ChAdOx1-S and 1,500,746 of Ad26.COV2-S have been administered in Italy during the considered interval with overall 23,358/117,947 ICSRs related to ChAdOx1-S (19.8 %) and 1,580/117,947 related to Ad26.COV2-S (1.3 %). A total of 134 reports after vaccination with adenoviral vaccines were identified according to the inclusion criteria, of which 107 cases were defined as thrombotic thrombocytopenia (95 following ChAdOx1-S and 12 after Ad26.COV2-S). 27 reports were defined as "not case" (level 5, Brighton) on the basis of clinical examination or investigation, or because of the presence of heparin as a concomitant drug. Furthermore, 3 reports were excluded because of a hereditary thrombophilia or a previous history of other thrombotic episodes. Seventy-seven cases were classifiable as BCG levels 1, 2, and 3 (definite, probable and possible cases, respectively) with an overall reporting rate at about 1 case per approximately 200,000 doses administered. Women aged 30 to 49 years showed the highest reporting rates. Conclusion: In Italy, the rates of thrombotic thrombocytopenia following COVID-19 immunisation with viral vector vaccines are in line with those reported in other Countries.

Associations of the COVID-19 pandemic with social well-being indicators in Mexico.

BACKGROUND: Public health measures for COVID-19 containment have implied economic and social life disruptions, which have been particularly deleterious in low- and middle-income countries (LMIC) due to high rates of informal employment, overcrowding, and barriers to accessing health services, amongst others social determinants. Mexico, a LMIC, is a country with a high COVID-19 mortality in which there has been a very limited governmental response to help mitigate such COVID-related disruptions. This study analyzes the association of the first wave of the COVID-19 crisis in Mexico with four well-being indicators: income, employment, anxiety, and food security. METHODS: It uses pooled cross-sectional data (n = 5453) of five monthly nationally representative surveys collected between April and August 2020. Probit models are estimated to assess the association of the pandemic with job loss and anxiety; a multinomial logistic regression is estimated for food security, and an ordinary least squares regression assesses the association between the pandemic and changes in household's income. RESULTS: Females were significantly associated with worse outcomes for the 4 well-being measures with an average reduction of 2.3% in household income compared to pre-COVID-19 levels, an increased probability (6.4 pp) of being in a household that had lost jobs, decreased probability of food security (6.9 pp), and an increased risk of anxiety symptoms (8.5 pp). In addition, those with lower SES and household with children also reported worse outcomes for employment, income and food security. The month variable was also statistically significant in these models suggesting that as more months of the pandemic elapsed the effects persisted. CONCLUSION: The currents study documents how the COVID-19 pandemic is associated with different well-being indicators in a LMIC. It suggests the urgent need to take actions to support vulnerable groups, particularly women, households with children and those in the lowest SES. If policy actions are not taken, the pandemic will increase social and gender disparities, and will jeopardize childhood development.

CHEST CT BODY COMPOSITION CHANGES at 3 and 6 MONTHS after SEVERE COVID-19 PNEUMONIA

Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.

Du suivi Post-Covid au Covid-Long : Score pronostic à partir d'une prise en charge holistique

Introduction Le COVID long est un problème de santé publique émergent manquant à ce jour d'une définition claire (OMS). Les médecins généralistes, en première ligne, aurait besoin d'un outil holistique, reproductible et facile pour les aider à évaluer le pronostic d'évolution vers un Covid-long chez leur patient ayant contracté une infection par le Sars-Cov-19 Matériels et méthodes Depuis mai 2020 dans notre centre un suivi standardisé (tous les 3 mois) et pluri disciplinaire est proposé aux patients ayant fait une forme sévère (post hospitalisation) ou ambulatoire mais avec symptômes persistants. Ils sont inclus dans une cohorte de suivi longitudinale avec un recueil à chaque visite des auto questionnaires (qualité de vie : SF36, fatigue : Pichot,dyspnée : MRC,Borg, cognitifs : MoCa, Stress : SSPT) un examen clinique exhaustif, des avis spécialisés avec bilan sanguin et imagerie selon l'évolution. L'objectif de notre étude est de décrire l'ensemble de nos données sur les caractéristiques socio-clinico-biologiques des patients inclus (J0) avec au moins une consultation de suivi Post Covid > à 4 semaines (S4) ayant évolué ou pas vers un Covid-Long ( > 12S) pour construire un score composite du Covid-Long Résultats 201 patients ont été inclus, 190 analysés dont 55 % de femmes, d'âge médian de 55 ans, actif dans 60 % des cas (24 % domaine santé), 58 % avec une comorbidité à risque de forme sévère. L'épisode aigue en ambulatoire pour 85 (42.2 %) patients, en hospitalisation conventionnelle pour 76 (37.8 %) ou en soins intensif/réanimation pour 40 (20 %). Une corticothérapie et une oxygénothérapie ont été prescrite pour respectivement 78 (38.8 %) et 114 (56.7 %). 49 (24.4 %) patients ont décompensé ou découvert (7 %) une maladie chronique. En moyenne les patients ont eu 2,6 visites et 48 % d'entre eux ont un suivi de plus de 12 mois. A S12 du suivi, 122 patients ont le statut de COVID Long (CL+) avec un nb moyen de symp = 3,6+/-2,2 (1-10) et 68 sont guéris (CL-). En analyse uni variée les FDR de CL+/CL- sont 1) le sexe féminin (p=0.004), un âge< à 65 ans (p=0.002) et être personnel de santé (p=0.022). 2) à J0 : anosmie/agueusie (p=0.011), myalgies (p=0.041) et épisode initiale ambulatoire (p=0.002). 3) à S4 : une dyspnée [échelle de Borg ≥ 3 (p=0.003)+ mMRC ≥ 1 (p=0.036)] et une Fatigue sévère [Pichot ≥ 20 (p<0.001)]. Dans le modèle de régression logistique multivariée, les FDR de CL+ sont à J0 d'avoir un âge < à 65 ans et fait un COVID aigue peu sévère avec prise en charge en ambulatoire avec respectivement OR 2.4 (IC95 : [1.0 ; 5.4]) et OR 2.3 (IC95 : [2.3 ; 4.6]). 2) à S4 post COVID d'avoir des difficultés cognitives OR 6.046 (IC95 : [1.82 ; 20.1]) et les signes fonctionnels psychiatriques OR 5.9 (IC95 : [1.7 ; 20.4]) ainsi qu'une Fatigue sévère OR 5.4 (IC95 : [1.2 ; 24.1]). En modélisant nos résultats nous avons construit un score composite comme outil pronostique de Covid-Long. Dans la formule chaque item en gras devra etre remplacé par 0 ou1 selon abscence ou presence, femme (1) et age en chiffre. =1/(1+(EXP((-1)*((-2,745)+(-0,329)*Femme+0,005*AgeQuantitatif +0,589*ambulatoire +(-0,418)*FDR-HCSP+0,9*Symptômes<5+(0,181)*Borg > 3+0,263*mMRC > 1+1,694*Pichot > 20+1,72*anosmie/agueusie+1,799*DifficultésCognitives+1,766*SymptomesPsychiatriques+2,008*DiagnosticDifferentiel))) Conclusion Ce score, apres une validation externe, nous permettra d'évaluer le pourcentage de risque d'évoluer vers un COVID long qu'aura chaque patient d'après ses données du J0 et de sa première consultation post covid. Cette étude objective à nouveau la nécessité de chercher à la fois la présence des symptômes mais aussi de les quantifier par des échelles simples et reproductibles. Aucun lien d'intérêt

Symptômes cardiaques en Post Covid : bilan cardiaque ? Pour qui ? Quand ? Comment ?

Introduction Dans le contexte de pandémie de Sars-Cov-19 avec des atteintes cardiovasculaires mal caractérisées, nous réalisons depuis mai 2020 une étude prospective, observationnelle, de cohorte centrée sur une évaluation et un suivi cardiovasculaire systématique chez des patients, quel que soit leur profil cardiovasculaire, ayant survécu à un épisode de Covid-19 modéré ou sévère (IDRCB: 2020-A01576-33) Matériels et méthodes A S4, S24 et S48 d'une infection avec PCRSars-Cov-19 positive, les patients inclus bénéficient d'une consultation clinique de cardiologie avec 1) ECG 2)Prélèvement sanguin troponine T, NT-proBNP, D-Dimères, bilan d'hémostase 3)Échocardiographie trans-thoracique (ETT) + écho-doppler veineux « 3 points » à 1 et 12 mois 4)IRM cardiaque et Angioscanner thoracique selon les recommandations internationales. Nous proposons ici une analyse intermédiaire de nos résultats après 18 mois du début de l'etude. Résultats 124 patients ont été inclus, avec un sex ratio de 1/2, d'âge médian de 55 ans, 58% avec une comorbidité à risque de forme sévère dont 38% de pathologie cardio-vasculaire, tabagisme actif dans 13% des cas .La prise en charge initiale était en ambulatoire (42.2%)en hospitalisation conventionnelle(37.8%) ou en soins intensif/réanimation(20%). Une maladie chronique a décompensé chez 24.4%des patients ou a été découverte chez 7% et 8% ont présenté une maladie thrombo-embolique et 2 patients une pericardite et 3 un trouble du rythme en phase aigüe. Dans le suivi, la présence de signes cardiologiques (douleur thoracique, syncope, palpitation, dyspnée de classe III ou IV NYHA, signes congestifs d'insuffisance cardiaque gauche ou droite, frottement péricardique, anomalies ECG du segment ST, des ondes T, élargissement du QRS, bloc atrio-ventriculaire du 2ème ou 3ème degré) était retrouvée chez 33% des patients à S4, 28% àS12, 22% àS24 et 14% à S48. Une ETT a été réalisée chez 60 patients et anormale chez 12 (20%) avec hypokinésie septale (8) une pericardite (2) ou HVG (2), une IRM cardiaque chez 41 patients et anormale chez 12 (29%) avec 10 myocardites et 2 péricardites. Tous les holter-ECG étaient normaux (4/4). Entre S4 etS12, 28% des patients avaient des D-Dimeres élevés (>0,5) et 25% une anomalie de la tropo/ NT-proBNP. Tous les patients avec une elevation des DDimeres avec une imagerie cardiaque anormale. Aucun lien n'est retrouvé entre le degré de sévérité initial, les co morbidités et les complications cardio-vasculaires post Covid sur le long terme. Conclusion Notre étude retrouve une importante prévalence des symptômes cardiaques même si ces derniers semblent disparaitre spontanément après 1 an de suivi. Nous ne disposons pas, à ce jour, de stratégie rentable pour exclure une pathologie CV sévére (myocadite pericardite) mais les consensus d'expert (https://doi.org/10.1093/eurheartj/ehac031) considèrent comme raisonnable de dépister les personnes à haut risque d'atteinte cardiaque ou avec un nouveau diagnostic CVpost-COVID-19 ainsi que les athlètes. Aucun lien d'intérêt

Real-time genotyping-based breast cancer risk assessment in MyPeBS, an international randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS)

Background: Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach. Methods: MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants. Results: As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer;72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality;and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks). Conclusions: Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants. Clinical trial identification: NCT03672331. Legal entity responsible for the study: Unicancer. Funding: European Commission and French National Cancer Institute. Disclosure: S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Exact Sciences;Financial Interests, Institutional, Advisory Board: Novartis;Financial Interests, Institutional, Advisory Board: Pierre fabre;Financial Interests, Institutional, Advisory Board: Orion;Financial Interests, Institutional, Advisory Board: Sanofi;Financial Interests, Institutional, Advisory Board: Rappta;Financial Interests, Institutional, Advisory Board: Cellectis;Financial Interests, Institutional, Advisory Board: Isis/servier;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Seagen;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: MSD;Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare;Financial Interests, Institutional, Invited Speaker: Roche Genentech;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Puma;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Orion;Financial Interests, Institutional, Invited Speaker: Sanofi;Financial Interests, Institutional, Funding: GE;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho;Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife;Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI;Financial Interests, Personal, Advisory Role: Amaris;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Sensorion;Financial Interests, Personal, Advisory Role: Biophytis;Financial Interests, Personal, Advisory Role: Servier;Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.

National informative system for surveillance of hazardous exposures and poisonings (SIN-SEPI). surveillance of exposures to detergents: an example of collaboration between the national institute of health, Poison Centers and the ministry of health

This report describes the exposures to detergents and related products (e.g., borderline disinfectants) managed by the Poison Control Centres of Bergamo and Foggia in the period 2016-2020. Descriptive analysis was conducted using tables and graphs and the differences between population subgroups were analysed using the X2 test. There is an excess of non-hospital calls (70.4%) compared to the expected value, probably influenced by the lockdown 2020 due to COVID-19 pandemic. A focus for the year 2020 highlighted an excess of exposures to cleaning products (p < 0.05) and borderline disinfectants (p< 0.001) in the months of lockdown. Another focus on exposures to washing machine detergents in soluble packaging for single use confirms that children (< 6 years) have a higher risk to be exposed to these products (< 6 year: 88.1%) compared to other laundry detergents (< 6 years: 66.4%), (p < 0.001), despite the preventive measures provided by the Regulation (EC) no. 1272/2008.

Breastfeeding media coverage and beliefs during the COVID-19 pandemic in Mexico: implications for breastfeeding equity.

BACKGROUND: Because breastfeeding offers short- and long- term health benefits to mothers and children, breastfeeding promotion and support is a public health priority. Evidence shows that SARS-CoV-2 is not likely to be transmitted via breastmilk. Moreover, antibodies against SARS-CoV-2 are thought to be contained in breastmilk of mothers with history of COVID-19 infection or vaccination. WHO recommends direct breastfeeding as the preferred infant feeding option during the COVID-19 pandemic, even among women with COVID-19; but conflicting practices have been adopted, which could widen existing inequities in breastfeeding. This study aims to describe how information about breastfeeding was communicated in Mexican media during the pandemic and assess Mexican adults' beliefs regarding breastfeeding among mothers infected with COVID-19. METHODS: We conducted a retrospective content analysis of media coverage on breastfeeding in Mexico between March 1 and September 24, 2020, excluding advertisements. For the content analysis, we performed both a sentiment analysis and an analysis based on strengths, weaknesses, opportunities, and threats (SWOT) for breastfeeding promotion. Additionally, we conducted a descriptive analysis of nationally representative data on adults' beliefs about breastfeeding from the July 2020 round of the ENCOVID-19 survey in Mexico and stratified the results by gender, age, and socioeconomic status. RESULTS: A total of 1014 publications on breastfeeding were identified on the internet and television and in newspapers and magazines. Most information was published during World Breastfeeding Week, celebrated in August. The sentiment analysis showed that 57.2% of all information was classified as positive. The SWOT analysis indicated that most information focused on current actions, messages, policies, or programs that enable breastfeeding (i.e., strengths) or those not currently in place but that may enable breastfeeding (i.e., opportunities) for breastfeeding promotion. However, ENCOVID-19 survey results showed that 67.3% of adults living in households with children under 3 years of age believe that mothers with COVID-19 should not breastfeed, and 19.8% do not know whether these mothers should breastfeed. These beliefs showed differences both by gender and by socioeconomic status. CONCLUSIONS: While the Mexican government endorsed the recommendation on breastfeeding during the COVID-19 pandemic, communication was sporadic, inconstant and unequal across types of media. There was a widespread notion that mothers with COVID-19 should not breastfeed and due to differences on beliefs by socioeconomic status, health inequities could be exacerbated by increasing the risk of poorer breastfeeding practices and preventing vulnerable groups from reaping the short and long-term benefits of breastfeeding.

Risk of COVID-19 hospitalization/mortality in patients with rheumatic disease treated with chloroquine/hydroxychloroquine or other conventional DMARDs in Italy: A large-scale nested casecontrol study

Objective: Chloroquine (CLQ)/hydroxychloroquine (HCQ) are two of the most studied drugs for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are very limited data on the effect of treatment of patients affected by rheumatic diseases with HCQ/CLQ and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) on COVID-19. The aim of this study is to investigate the hypothesis that treatment of rheumatic diseases with hydroxychloroquine (HCQ)/chloroquine (CLQ) as compared to other conventional disease-modifying anti-rheumatic drugs (cDMARDs) might decrease the COVID-19-related risk of hospitalization and mortality. Methods: This large-scale case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia (Emilia Romagna) Local Health Unit, covering a total of 25.1 million inhabitants. Claims databases were linked to loco-regional COVID-19 surveillance registries from the same catchment area through unique fully-anonymized patient identifiers. Risk of COVID-19-related outcomes was estimated as odds ratios (ORs) along with 95% confidence intervals (CIs), using a multivariate conditional logistic regression analysis, by comparing HCQ/CLQ vs methotrexate (primary comparator) and other cDMARDs (secondary comparator). In addition, the same risk for HCQ/CLQ, methotrexate and other cDMARDs separately vs nonuse of these drugs as well as for presence of rheumatic diseases vs. absence in a non-nested population was investigated. Results: From the cohort of cDMARD users, 1275 cases who were hospitalized due to COVID-19 were identified and matched to 12,734 controls. When compared to recent use of methotrexate, no statistically significant association between recent HCQ/CLQ monotherapy with COVID-19 hospitalization (OR 0.83 [95% CI, 0.69 to 1.00]) or mortality (OR 1.19 [95% CI, 0.85 to 1.67]) was observed. A statistically significant lower risk was found when comparing recent use of HCQ/CLQ to treatment with other cDMARDs and glucocorticoids concomitantly. In the sensitivity analysis in the non-nested population, HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use, whereas a mild statistically significant increased risk for recent use of both methotrexate as monotherapy (OR 1.19 [95% CI, 1.05 to 1.34]) or other cDMARDs (OR 1.21 [95% CI, 1.08 to 1.36]) vs non-use was found. Finally, the presence of rheumatoid arthritis or systemic lupus erythematosus was not associated with COVID-19 hospitalization (OR 0.98 [95% CI, 0.89 to 1.07]) or mortality (OR 0.88 [95% CI, 0.74 to 1.05]). Conclusion: Prior exposure to HCQ/CLQ in rheumatic patients was not associated with a protective effect against COVID-19-related hospitalization and mortality. On the contrary, an increased risk in patients receiving other cDMARDs was observed when compared to non-use, especially in those patients concomitantly treated with glucocorticoids. This is likely attributable to a synergistic immunosuppressive effect, leading to increased risk of severe SARS-CoV-2 infection.

Online Hackathons as an Engaging Tool to Promote Group Work in Emergency Remote Learning

In 2020, due to the COVID-19 pandemic, educational activities had to be done remotely as a way to avoid the spread of the disease. Instead of shifting to an online learning model, it consisted of a transition to what was called Emergency Remote Teaching. This is a strategy to keep activities going on until it is safe again to return to the physical facilities of universities. This new setting became a challenge to both teachers and students. The lack of interaction and classroom socialization became obstacles for students to continue engaged. Before the pandemic, hackathons - short-lived events (1 to 3 days) of intensive collaboration to develop software prototypes - were being explored as an alternative venue to engage students in acquiring and practicing technical skills. In this paper, we present an experience report on the usage of an online hackathon as a resource to engage students in the development of their semester project in a distributed applications course during this emergency remote teaching period. We describe the intervention and analyze the students' perspective of the approach. One of the findings was the importance of the Discord communication tool - used by students for playing games - which helped them socialize and be engaged in synchronous group work, "virtually collocated". © 2021 ACM.

Characterisation of SARS-CoV-2-infected children developing neutralising antibodies

Background: Further knowledge on adaptive immunity to SARS-CoV-2 (CoV-2) in children is needed in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT), alongside antigen (Ag) specific cellular response, in relation to virus load in nasopharyngeal swabs. Methods: We analysed 42 CoV-2 patients at 7 days after symptoms onset. CoV-2 viral load (VL) was measured by RT-PCR and digital droplet PCR on longitudinal samples of nasopharyngeal swabs (NP). Virus infectivity (FFU) was tested by virus focus forming assay. CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and neutralization assay (PRNT). CoV-2-specific CD4-CD40L+ T-cells and Spike specific B-cells were analysed by flow cytometry. Plasma proteomic profiling was measured by 2 Olink panels. We calculated the area under the curve (AUC) of the viral load from NP collected every 48 hours up to undetectable VL. Mann-Whitney was used to compare means in individuals with neutralizing activity (PRNT+) or not (PRNT-);linear regression was used to evaluate the associations between virus load and infectivity over time. Principal component analysis (PCA) was used to analyse proteomic data. Results: Higher VL was found in seronegative patients expressed in terms of both CoV-2 Ab (p=0.003) and PRNT (p=0.0007). Similarly, lower FFU was associated with higher CoV-2 Ab (p=0.003;rho=-0.67) and PRNT (p=0.023;rho=-0.46). Further, the AUC of the viral load in NP showed an inverse correlation with CoV-2 Ab (p=0.031;rho=-0.54). Development of humoral response was associated with the presence of CoV-2 specific IgD-CD27+ B cells, with a higher frequency of CoV-2 specific B cells found in seropositive compared to seronegative (p=0.001). Besides, individuals developing neutralizing Ab had higher frequency CD4-CD40L+ T-cells compared to PRNT- (p=0.03). The plasma proteome confirmed the association between cellular and humoral CoV-2 immunity, with PRNT+ showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). Conclusion: This work provides a virological and immunological characterization of SARS-CoV-2 infected children presenting a differential Abmediated neutralizing activity. It demonstrates that children with neutralizing antibodies present reduced viral load, faster virus clearance and lower in vitro infectivity. These data provide information that can drive vaccination endpoints and quarantine measures policies.

Asymptomatic sars-cov-2 children have lower infectivity and intact memory responses

Background: SARS-CoV-2 (CoV-2) infected children often range from being paucysymptomatic to fully asymptomatic. The impact of this population on the epidemics due to their ability to transmit the virus and achieve protective immunity has been poorly defined. We explored CoV-2 infectivity potential and anti-CoV-2 cellular (CD8, NK and B) and humoral response in symptomatic (SY) and asymptomatic (AS) CoV-2 infected children, screened for a family member resulted infected. Methods: CoV-2 viral load was measured by RT-PCR and digital droplet PCR (ddPCR) on longitudinal samples of nasopharyngeal swabs in 9 AS and 33 SY (samples were paired according to symptoms'onset for SY and first family contact for AS). Virus infectivity was tested by Virus focus forming assay (FFA). CoV-2 antibodies were investigated by Diasorin (CoV-2 Ab) and Ab-mediated neutralization activity (PRNT) at diagnosis, (samples collected >5 days from symptoms onset in SY, or from first family contact in AS were excluded from this timepoint), and in the convalescent phase (CP) (10-14 days after infection). Cellular response was analyzed by flow cytometry: 1) Ag-specific B cells, by a S1+S2 CoV2-R-PE probe;2) Ag-specific CD8+T cells by ICAM+;3) natural-killer (NK) phenotype. Mann-Whitney was used for comparison;linear regression was used to evaluate the associations between virus load and infectivity. Results: AS showed lower viral load (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Virus infectivity was associated with ddPCR (rho=0.66;p=0.002). ASY and SY showed similar levels of CoV-2 Ab and PRNT, at both diagnosis and at follow up. During the CP, the proportion of CoV-2 Ab negative was 33,3% for both groups and PRNT was negative in 16,6% and 15,7% of AS and SY respectively. Anti-CoV-2 cellular immunity was comparable between ASY and SY. Indeed Ag-specific B cells and CD8 T cells were detectable despite symptomatology and no major differences were found between the groups. Total NK frequency was similar between the groups, while a regulatory NK subset (CD56bright NK cells) was higher in AS compared to SY (p=0.01). Conclusion: These data show that AS have a lower infectivity potential compared to SY suggesting that mitigated restrictive measures or alternative screening may be considered for this population. In addition, these patients showed an intact ability to produce humoral and cellular CoV-2 specific responses hence contributing to achieve herd immunity as much as SY.

Possible role of vitamin D in Covid-19 infection in pediatric population.

PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and ß-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.