COVID-19 vaccination in adults with congenital heart disease: Results of 1-year prospective study

Background: Adults with congenital heart disease (ACHD) are a vulnerable population. Routine vaccination is the only strategy to prevent a lifethreatening infection. However, concerns on the cardiac safety and efficacy of COVID-19 vaccines have been raised. Aim(s): To assess safety and efficacy of available COVID-19 vaccines in ACHD patients. Method(s): Data on COVID-19 infection and vaccines including booster doses and any suspected or confirmed adverse events were prospectively collected for all ACHD patients attending our tertiary centre from the beginning of the vaccination campaign (March 2021). A group of 75 healthy volunteers, matched per age and sex, was included for comparison. Antispike IgG titre was routinely obtained at the ACHD clinic. Patients' attitude towards COVID-19 was explored with a questionnaire. Result(s): As of February 2022, 498 ACHD patients (36.7+/-16 years, 54% male,69% with moderate-complex defects, 48% with advanced physiological stage) were enrolled. Four hundred and sixty-one (92%) were fully vaccinated: The type of vaccine was Pfizer-BioNTech for 399 (86%) patients, Moderna for 20 (4%) and AstraZeneca for 26 (6%), 9 received a mixed vaccine regimen (2%). Forty-two (9%) had a history of previous COVID-19 infection and therefore received only one dose. Two-hundred and sixty-nine (58%) patients received a booster dose. Adverse events were mainly mild and transient. One patient complaining of chest pain following administration of mRNA-based vaccination was diagnosed with acute pericarditis, which made full remission after appropriate therapy. Two patients reported a non-specific increment of inflammatory markers. No other severe adverse events were reported. Thirty-seven (7%) refused COVID-19 vaccination being scared of potential cardiac/extra-cardiac adverse events. Among those not-vaccinated, 9 (24%) had a history of previous mild COVID-19 infection. IgG titre was measured in 243 patients at 1915 [835-5934] BAU/ml, which was significantly higher compared to controls (1196 [827-2048] BAU/ml, p=0.002). Three ACHD patients contracted COVID-19 infection after the first dose, while 65 (14%) fully vaccinated patients tested positive for COVID-19, all with mild to moderate symptoms. COVID-19 symptoms duration was significantly longer in case of infection before vaccination (10 [2.7-15] vs 3 [1.2-7], p=0.03). One Fontan patient was tested positive for COVID-19 twice, before and after COVID-19 vaccination, requiring hospitalization in both cases. Four hundred and seven patients completed the questionnaire: 128 (31%) declared to be scared of potential cardiac effects of the vaccine and that the discussion with the ACHD cardiologist was crucial to decide to undergo COVID-19 vaccination. Conclusion(s): Our data provide real-world evidence on COVID-19 vaccines safety and efficacy in ACHD patients. Patients' education from the ACHD team may play a key role in vaccine acceptance in this vulnerable population.

COVID-19 AS A POSSIBLE CAUSE OF MODIFICATION OF THE INTERNATIONAL CONTRACT: AN INTERPRETATIVE PROPOSAL IN THE LIGHT OF THE LEX ARB ITR I AND THE APPLICABLE SUBSTANTIVE RULES

In recent months it has been discussed whether the pandemic generated by Covid-19 can be established as a possible ground for contract modification due to hardship. This paper reviews this concern specifically in international commercial contracts, arguing that, based on the arbitral tribunal's obligation to consider commercial stipulations and usages in the resolution of the dispute in question, even when the law applicable to the merits of the case is highly probable that this thesis will be accepted. For this purpose, we will review the various elements that are necessary to understand this assertion. © 2022, Thomson Reuters Brasil Conteudo e Tecnologia. All rights reserved.

A Machine Learning approach for shared bicycle demand forecasting

More than 9 million bicycles are shared worldwide through more than 3.000 Bicycle Shared Systems (BSS). Investigating possible behaviours related to the demand for these services will optimize their success. The purpose of this research is to identify the impact of weather conditions, covid and pollution on the usage of BSS. Different machine learning algorithms are studied and used to analyze the different variables. Results were consistent with the literature and theory. In what concerns the algorithms, random forest and multi-layer perceptron regressor performed better, showing a better prediction power. © 2022 IEEE Computer Society. All rights reserved.

Covid-19 in patients with chronic lymphocytic leukemia: Clinical outcome and Band T-cell immunity during 13 months in consecutive patients

We studied the clinical and immunological outcomes of covid-19 infection in strictly consecutive patients with CLL from a well-defined area during the first 13 months of the pandemic. Sixty patients with a median age of 71 years (range 43-97) were identified. Median CIRS was 8 (4-20), median BMI 25 (19-42) and 65% were men. Patients had indolent CLL (n=38), were previously treated (n=12) or had ongoing therapy (n=10, among which seven received BTKi). Forty-six patients (77%) were hospitalized due to severe covid-19 and among them, 11 (24%) were admitted to the intensive care unit (ICU). Severe covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except for comorbidities (CIRS >6, p<0.05). Fourteen patients (23%) died;age ≥75 years was the only significant risk factor (p<0.05, uni- and multivariate analyses). Comparing months 1-6 vs. 7-13 of the pandemic, death rates were reduced from 32 to 18%, ICU admission from 37 to 15% and hospitalizations remained frequent (86 vs. 71%). Seroconversion occurred in 34/41 tested patients (83%) and anti-SARS-CoV-2 antibodies remained detectable at 6 and 12 months of follow-up in 17/22 and 8/11 patients, respectively. In-depth immunological analysis revealed that 13/17 tested patients had neutralizing antibodies (including all 12 patients that were also seropositive in conventional serology in this cohort), and 19/28 (68%) had antibodies in saliva. SARS-CoV- 2-specific T-cells (IFN-gamma ELISpot) were detected in 14/17 patients (82%). We conclude that covid-19 in non-selected CLL patients continued to result in a high admission rate even among young early-stage patients. A robust and durable B and/or T cell immunity was observed in most convalescents.

Cessation of ibrutinib results in reduced infections and durable remissionsfirst analysis of an on-off-repeat study in patients with chronic lymphocytic leukemia

Ibrutinib is used continuously in CLL. This phase 1b trial (n=22) explored on-off-repeat dosing to reduce toxicity and costs. After 12 months, 73% remained in the first off-phase irrespective if initial CR/PR or TP53 aberration. Reduced/eliminated hematomas, nail/skin changes, and notably, grade 3-4 infections (from 55% in the year before to 5% during similarly long off-phase) were observed (all p<0.01). Increased Treg and exhausted T-cells (p=0.01) were observed. Six patients restarted ibrutinib at early progression and all remain drug-sensitive. Conclusion: Withholding ibrutinib appears safe and switching on BTK-signaling should be explored to improve covid-19 vaccine efficacy while reducing infections and side effects.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

CLIMATE-NEUTRAL and SMART CITIES: A EUROPEAN POLICIES' OVERVIEW

Cities are increasingly defined as one of the most important actors in the transition to a climate-neutral Europe. The reasons are multiple, and some of them are the increasing number of inhabitants and the demographic trends;the percentage of emissions produced by the urban areas;the innovation potential, thanks to the concentration of creativity and knowledge;the political dimension that helps in involving the citizens;the economical role and the fact that cities and towns are transport networks' hubs. Recognizing this crucial role, the European Union is updating its own policies on the matter, promoting challenging strategies as the Horizon Europe Mission on "Climate-neutral and Smart Cities". This article analyses the European policies and strategies aimed at tackling the climate change in the urban areas. They are making the cities the forefront where to speed up the transition and promote flagship actions able to pave the way for reaching the European Green Deal goals. Moving from the main policies, this article investigates the overall ratio behind them and presents the tools and the actions promoted by the European Commission to support the local authorities in recognizing and facing the challenge, which is at the very core of the New Generation EU programme and a key enabler in designing the post-Covid Europe. On the other hand, this article briefly presents the main activities that cities are expected to develop in the next decade in order to fully contribute to the European ambition to be the first carbon-neutral continent on the planet by 2050. © 2021 WITPress. All rights reserved.

Facing COVID-19 pandemic in the neonatal and obstetrics department: From challenge to opportunity. The experience of Hospital of Castelli

INTRODUCTION COVID-19 pandemic has represented an unexpected stress test for Italian Health System, and a real challenge for health workers and organizations. Hospital of Castelli, opened in December 2018 as the Hub of ASLRM6, with a catchment area of more than 570,000 persons, was identified, since the beginning of pandemic, as the unique birth point of the territory, supporting safety and organization for newborns and families. This decision allowed reorganization and definition of specific care pathways for Neonatal and Obstetric Department. METHODS The Neonatology-Pediatrics and Obstetrics- Gynecology Complex Units, both located on the 1st floor of the hospital, close to Delivery rooms, were protected by isolating the entire 1st floor from the upper and ground floors, hosting COVID wards. All pregnant women were screened, before admission to delivery room, with RT-PCR for Sars-CoV- 2 naso-pharyngeal (NF) swab performed within 48 h prior to delivery ('green' pathway). In case of imminent delivery, a 'red' pathway for unknown or suspected Sars-CoV-2 pregnant women was defined, as a part of the delivery Unit, but completely separate and independent from the green pathway. Mother and newborn managed in the red pathway, waiting for the result of RT-PCR, if in good clinical conditions, were put in the same, single room, strictly isolated in a separate section of Obstetric ward, 2mt away from each other. Mother could start breastfeeding soon after delivery, wearing individual protection devices. If neonatal symptoms or need for admission in Neonatal ward were present, newborn was put in a separate, isolation room in the Neonatal Pathology Unit. If maternal RT-PCR NF swab resulted positive, mother and newborn were transferred, within first hours after delivery, to one of the COVID-Hub hospitals for Obstetrics and Neonatology in Rome (Policlinico 'A.Gemelli' or Policlinico Umberto I). Newborns of Sars-CoV-2-positive mothers underwent RT-PCR for Sars-CoV-2, prior to transfer. RESULTS From 31 March 2020 to 31 March 2021 a total of n.5 mothers resulted positive for Sars-CoV-2 and were transferred with their newborns to a COVID-Hub hospital. All the positive mothers were asymptomatic or paucisymptomatic;their newborns were in good clinical conditions and all resulted negative at RT-PCR for Sars-CoV-2 NF swab performed prior to the transfer. No Sars-CoV-2 outbreaks developed in our hospital in the period studied. Positive mothers and their newborns had a good clinical outcome and were discharged from the COVID hospital within 7-10 days after delivery. They underwent home follow-up by local medical care service (SISP) and basic pediatricians, supported, where possible, by telemedicine services. CONCLUSIONS an appropriate organization, based on specific, defined and separate clinical pathways, for COVID-19- unknown or suspected mothers and infants, is crucial for facing the ongoing pandemic, providing safety and good quality medical care for mothers and newborns.

Incidence, typology and measures of prevention and treatment of skin lesions associated with the use of personal protective equipment in health care professionals during the COVID-19 pandemic in Spain Collaborative study GNEAUPP-Cátedra de estudios avanzados en heridas GNEAUPP - FSJJ - Universidad de Jaén

Introduction: The recent COVID-19 pandemic has represented the use by health care professionals (HCP) of different personal protective equipment (PPE), resulting in the appearance of skin injuries associated with PPE (PPE-SI). Knowing the epidemiology, characteristics and factors related to the use of different types of PPE and the prevention and treatment of PPE-SI can be very useful to understand the scope of the problem and to define strategies for its prevention and treatment in possible future pandemics. Methods: To this end, the GNEAUPP proposed the performance of a cross-sectional study, in the geographical area of the Spanish state, by means of a self-administered survey using a Google forms questionnaire. The study universe was HCP, from any discipline and from any level of care or type of institution with patients who have been in contact with COVID-19 patients or COVID-19 suspects and have used PPE during the first wave of the COVID-19 pandemic in Spain. Main results: We obtained 2078 questionnaires, 75.5% from nurses, 10.79% from nurse aids, and 6.6% from physicians. Of these, 84.7% were women and 15.3% were men with an average age of 43.7 years. In 18.2% of the cases the institution of the professional had a protocol for the prevention of PPE-SI, in 10.2% the professional did not know if it existed or not and in the remaining 71.3% the institution did not have such a protocol. 29.9% of the professionals always used some prevention product and 25.3% sometimes. 52.4% of respondents reported having submitted at least one PPE-SI, of which 39% had submitted one, 35.8% two, 14.3% three, 2.2% four and 8.6% more than four. In relation to PPE-SI, 74.3% were defined as pressure injuries (PI), 11% were friction injuries (FI), 8.5% were combined or multicausal injuries (CMCI) and 6.1% were skin injuries associated with moisture (MASI). The mean duration of incident injuries was 11.6 days (9.7 days for PI, 10.2 days for FI, 19.9 days for CMCI and 19.4 days for MASI). More detailed Information is presented in the paper by type of device causing, typology and severity of injuries per device as well as preventive measures used.

Ongoing COVID-19 vaccination in Italy. Online survey of gender- and age-related side effects

Background: Evidences suggest that gender may influence the response to various vaccines in terms of immune response and side effects. Whether similar differences also occur with COVID-19 vaccine, is still uncertain. Materials and Methods: In March 2021, we advertised a short anonymous questionnaire (Google forms) to medical doctors, nurses, postgraduates, students and general public, consisting of 30 questions exploring 16 possible side effects (local pain or hardness, swelling, redness, allergic reaction, tiredness, headache, sleep disorders, myalgia, fever, enlarged lymph nodes, irritability, diarrhea, urticaria, vomiting, anaphylaxis). We recorded side effects after 1st dose, and within one week after 2nd dose. Data were analyzed according to gender and seven age groups. Results: We received 1,034 questionnaires from all over Italy (369 males, 665 females, age range 20-83 years). Injected vaccines were Pfizer-BioNTech (96.9%), Astra-Zeneca (2.4%), Moderna (0.7%). Major adverse events were absent. Minor adverse events occurred with both 1st dose (76.0%) and 2nd dose (78.0%) and were invariably higher in females than in males (1st dose: 79.4% vs 69.9% p = 0.0006;2nd dose: 81.8% vs 70.7%, p = 0.00004). The significant cluster of adverse events were local pain, redness, hardness at the injection site, fever, sleep disturbances, headache, lymph nodes enlargement following both doses (0.00001 < p < 0.02). Effects disappeared within 48hrs in 80% of cases (range 1-7 days). The gender difference was confirmed in the age class 30-39 after 1st dose (85.8% vs 70%, in females and males, respectively p = 0.03), and in the age classes 30-39 (84.6% vs 75.5%, in females and males, respectively p = 0.03) and 40-49 (74.8% vs 57.9%, in females and males, respectively p = 0.02) after 2nd dose. Fever tended to be more frequent in females after the 1st dose (6.5% vs 3.8%) and became significantly higher after the 2nd dose (32.9% vs 17.3%, p = 0.00001). After 50 years of age, the rate of all the recorded adverse events was similar between genders. Conclusions: COVID-19 vaccines generate frequent, although mild side effects with a gender (female) prevalence, especially in the age range 30-49 years. The gender difference disappears after 50 years of age, thus pointing to possible involvement of sex hormones and attenuated immune response.

Incidence, typology and measures of prevention and treatment of skin lesions associated with the use of personal protective equipment in health care professionals during the COVID-19 pandemic in Spain

Introduction: The recent COVID-19 pandemic has represented the use by health care professionals (HCP) of different personal protective equipment (PPE), resulting in the appearance of skin injuries associated with PPE (PPE-SI). Knowing the epidemiology, characteristics and factors related to the use of different types of PPE and the prevention and treatment of PPE-SI can be very useful to understand the scope of the problem and to define strategies for its prevention and treatment in possible future pandemics. Methods: To this end, the GNEAUPP proposed the performance of a cross-sectional study, in the geographical area of the Spanish state, by means of a self-administered survey using a Google forms questionnaire. The study universe was HCP, from any discipline and from any level of care or type of institution with patients who have been in contact with COVID-19 patients or COVID-19 suspects and have used PPE during the first wave of the COVID-19 pandemic in Spain. Main results: We obtained 2078 questionnaires, 75.5% from nurses, 10.79% from nurse aids, and 6.6% from physicians. Of these, 84.7% were women and 15.3% were men with an average age of 43.7 years. In 18.2% of the cases the institution of the professional had a protocol for the prevention of PPE-SI, in 10.2% the professional did not know if it existed or not and in the remaining 71.3% the institution did not have such a protocol. 29.9% of the professionals always used some prevention product and 25.3% sometimes. 52.4% of respondents reported having submitted at least one PPE-SI, of which 39% had submitted one, 35.8% two, 14.3% three, 2.2% four and 8.6% more than four. In relation to PPE-SI, 74.3% were defined as pressure injuries (PI), 11% were friction injuries (FI), 8.5% were combined or multicausal injuries (CMCI) and 6.1% were skin injuries associated with moisture (MASI). The mean duration of incident injuries was 11.6 days (9.7 days for PI, 10.2 days for FI, 19.9 days for CMCI and 19.4 days for MASI). More detailed Information is presented in the paper by type of device causing, typology and severity of injuries per device as well as preventive measures used.