Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic.

OBJECTIVE: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. METHODS: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). RESULTS: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 0.026) remained inversely associated with abnormal HI scores. CONCLUSION: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

Trustworthy Government: The Obligations of Government & the Responsibilities of the Governed

Establishing trustworthy government is a major problem for contemporary democracies. Without public confidence, government faces considerable noncompliance with its policies, as has been the case with the reaction of some subpopulations to COVID safety requirements. The pressures on government today are numerous. The challenges are complex and the polity diverse. Creating confidence and thus willing compliance requires a demonstrated government competence. It also requires political leadership committed to the collective good and to forging a common identity among multiple subgroups while recognizing their distinctive differences and needs. Citizens are also crucial actors. It is incumbent upon a democratic citizenry that it recognizes its responsibilities to and interdependence with others in the polity as members of an expanded community of fate.

Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations.

Using molecular dynamics simulations, the protein-protein interactions of the receptor-binding domain of the wild-type and seven variants of the severe acute respiratory syndrome coronavirus 2 spike protein and the peptidase domain of human angiotensin-converting enzyme 2 were investigated. These variants are alpha, beta, gamma, delta, eta, kappa, and omicron. Using 100 ns simulation data, the residue interaction networks at the protein-protein interface were identified. Also, the impact of mutations on essential protein dynamics, backbone flexibility, and interaction energy of the simulated protein-protein complexes were studied. The protein-protein interface for the wild-type, delta, and omicron variants contained several stronger interactions, while the alpha, beta, gamma, eta, and kappa variants exhibited an opposite scenario as evident from the analysis of the inter-residue interaction distances and pair-wise interaction energies. The study reveals that two distinct residue networks at the central and right contact regions forge stronger binding affinity between the protein partners. The study provides a molecular-level insight into how enhanced transmissibility and infectivity by delta and omicron variants are most likely tied to a handful of interacting residues at the binding interface, which could potentially be utilized for future antibody constructs and structure-based antiviral drug design.

LONG-TERM OUTCOME OF CEREBRAL VENOUS THROMBOSIS DUE TO SARS-COV-2 VACCINE-INDUCED IMMUNE THROMBOTIC THROMBOCYTOPENIA

Background and aims: Since initiation of COVID-19 vaccination, cases of cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) have been reported. Reported in-hospital mortality varies between 20-50%, but data on longterm outcome of surviving patients with CVT-VITT are not available. Methods: We report follow-up data of CVT-VITT cases after COVID- 19 vaccination from an international registry. VITT was classified according to the Pavord criteria. Outcomes were mortality, functional dependency, relapse of VITT, new thrombosis, and new bleeding events. Results: Of 62 patients with CVT-VITT who survived initial hospital admission, follow-up data were available for 48/62 (77%) cases (32 (67%) definite VITT, 7 (15%) probable VITT, 9 (19%) possible VITT). Median time from diagnosis to last follow-up was 110 days (IQR 86-174). There were no new venous or arterial thrombotic events reported in any case. Among 35/44 (80%) cases that achieved clinical remission, 0/29 cases had a relapse of VITT. Major bleeding was reported in 1/45 (2%) cases (intracranial bleed). Mortality at follow-up was 1/48 (2%, 95%CI 0-11%). 44/48 (92%) cases had a modified Rankin Scale score of 0-2 at follow-up, compared to 32/46 (70%) at hospital discharge. 16/34 (47%) of cases had returned to work or school. Conclusions: In patients who survive the acute phase of CVT-VITT, long-term mortality is low and thrombotic and bleeding events are rare. Approximately half of the CVT-VITT patients at follow-up could resume all daily activities.

CHANGE IN MANAGEMENT AND DECREASE IN MORTALITY OF CEREBRAL VENOUS SINUS THROMBOSIS WITH THROMBOCYTOPENIA AFTER SARS-COV-2 VACCINATION

Background and aims: Cerebral venous sinus thrombosis with thrombocytopenia syndrome (CVST-TTS) is a rare adverse effect of adenovirus- based SARS-CoV-2 vaccines. After the autoimmune pathogenesis of TTS was discovered, treatment recommendations were issued. The aim of this study was to evaluate if adherence to treatment recommendations was associated with lower mortality. Methods: TTS was defined according to the Brighton criteria. Cases from a prospective international CVT registry with symptom onset within 28 days of adenovirus-based SARS-CoV-2 vaccination were analysed. Treatment recommendations, following the International Society of Thrombosis and Haemostasis, included use of immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusions, unless needed for surgery. Results: Out of 178 CVT cases from 117 centres in 19 countries reported between March 29 and September 3, 2021, 95 patients fulfilled inclusion criteria. Five of 37 (14%), 13/25 (52%), and 29/33 (88%) of patients diagnosed in March, April, and from May onwards, respectively, were treated according to recommendations. Proportion of patients diagnosed in March, April, and from May onwards who received immunomodulation increased from 19/37 (51%) over 15/25 (60%) to 30/33 (90%), and the percentage of patients who were treated with heparins [26/37 (70%), 4/25 (16%), 1/33 (3%)] and platelet transfusion [15/37 (41%), 4/25 (16%), 7/33 (21%), respectively] decreased accordingly. Mortality of patients treated according to recommendations was 14/47 (30%, 95%CI 19-44%) compared to 28/48 (58%, 95%CI 44-71%) in patients not treated according to recommendations (OR 3.30, 95%CI 1.41-7.71). Conclusions: Over time, adherence to treatment recommendations improved, and mortality rate of patients with CVST-TTS decreased.

DECOMPRESSIVE SURGERY IN CEREBRAL VENOUS SINUS THROMBOSIS WITH VACCINE-INDUCED IMMUNE THROMBOTIC THROMBOCYTOPENIA

Background and aims: Cerebral venous sinus thrombosis with thrombosis with thrombocytopenia syndrome (CVST-TTS) is a serious adverse drug reaction after adenoviral SARS-CoV-2 vaccinations. CVST-TTS patients may need decompressive surgery to avoid fatal brain herniation, but despite this intervention, many CVST-TTS patients die during the initial hospital admission. Here, we describe the characteristics and outcomes of CVST-TTS patients who underwent decompressive surgery and explore predictors of mortality in CVST-TTS patients. Methods: We used data from an ongoing international registry collecting data from patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March and 9 December 2021. TTS was defined in accordance with the Brighton Collaboration case definition. Results: Out of 97 CVST-TTS patients, 29 (30%) underwent decompressive surgery. All operated patients had an intracerebral haemorrhage before the surgery. In-hospital mortality was 19/29 (66%) in the operated and 23/68 (34%) in the non-operated group. In the operated group, the highest mortality rate was among patients who were in coma before the surgery (14/15, 93% vs 4/12, 33% in those not in coma), had bilateral absence of the pupillary response (7/7, 100% vs 8/16, 50% in patients with uni/bilateral pupillary response) and platelet count <50 x103/μL (11/14, 79% vs 6/12, 50% in cases with a platelet count ≥50 x103/μL). Conclusion: Mortality rate of CVST-TTS patients who underwent decompressive surgery is extremely high. Among the operated patients, coma before the surgery, bilateral absence of the pupillary response, and platelet count <50 x103/μL were the predictors of mortality.

Age stratified risk of cerebral venous sinus thrombosis after SARS-CoV-2 vaccination

Introduction: Cerebral Venous Sinus Thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of SARS-CoV-2 vaccination. The estimated background rate of CVST in adults is around 1 case per million per month, and CVST with thrombocytopenia accounts for 8% of all CVST. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. Methods: We estimated the absolute risk of any CVST, CVST with thrombocytopenia, and CVST without thrombocytopenia, within 28 days of first dose SARS-CoV-2 vaccination, using data from the European Medicines Agency's EudraVigilance database (until 13 June 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. Results: The absolute risk of CVST within 28 days of first dose vaccination was 7.5 (95%CI 6.9- 8.3), 0.7 (95%CI 0.2-2.4), 0.6 (95%CI 0.5-0.7) and 0.6 (95%CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95%CI 3.9-4.9), 0.7 (95%CI 0.2-2.4), 0.0 (95%CI 0.0-0.1) and 0.0 (95%CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the risk of CVST, both with and without thrombocytopenia, was the highest in the 18-24 years age group (7.3 per million, 95%CI 2.8-18.8 and 3.7, 95%CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia was the lowest in ChAdOx1 nCov-19 recipients ≥70 years (0.2, 95%CI 0.0- 1.3). Age <60 compared to ≥60 was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79;95%CI 2.98-11.24, p<0.001). Discussion: The risk of CVST with thrombocytopenia within 28 days of first dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S, comparing with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of mRNA vaccines for SARS-CoV-2.

Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a pathogenic coronavirus causing COVID-19 infection. The interaction between the SARS-CoV-2 spike protein and the human receptor angiotensin-converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide-thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID-19. However, the molecular-level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID-19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID-19 infection or reducing the severity of the disease.

Fraud and pandemics

Purpose: This study aims to draw out the common characteristics of frauds associated with pandemics and to identify any risks unique to them. Design/methodology/approach: It considers the range of frauds and their reporting lags and examines what is known about current frauds against individuals, businesses and government, principally using public and private sector data from Australia and the UK. Findings: The study identifies some novel crime types and methodologies arising during the current pandemic that were not seen in previous pandemics. These changes may result from public health measures taken in response to COVID-19, the current state of technologies and the activities of law enforcement and regulatory guardians. It shows that many frauds would occur anyway, but some specific – mainly online – frauds occur during pandemics, and because of large scale government assistance programmes to businesses and individuals, far more opportunities were created from COVID-19 than in previous eras. Social implications: The study concludes with a discussion of the policy implications for prevention, resilience and for private and public policing and criminal justice. It stresses that plans for future pandemics must include provisions for better early monitoring and control of fraud and associated procurement corruption and notes that these require greater political will and organisation. It recommends a more serious analysis of the impact of prevention communications outreach to citizens, businesses and government. Originality/value: The study uses fresh data on frauds from the private and public sectors and assesses some measures of control in a holistic way. © 2021, Emerald Publishing Limited.

All-cause mortality during the influenza season 2019-2020: comparison with previous influenza seasons in the territory of the local health authority "Central Tuscany", Italy.

Introduction: Because of the 24 months latency in the release of official data on causes of death, and in consideration of the limited testing capacity during the first pandemic wave, to estimate the COVID-19-related mortality in 2020, the evaluation of all-cause mortality excess is often used instead. Our study aimed at assessing whether in Central Tuscany, Italy, an excess all-cause mortality occurred in the 2019-2020 influenza season, which partly overlapped with the months of the first pandemic wave in which the impact of COVID-19 was the highest. Materials and Methods: Age- and sex-adjusted mortality rates for 2019-2020 influenza season were compared with those of influenza seasons 2009-2010 to 2016-2017. Results: No all-cause mortality excess was observed in the 2019-2020 influenza season, which, on the contrary, was characterized by the lowest all-cause mortality rate. Conclusion: Our finding can be explained by the imposition, in early March 2020, of a national lockdown, which came into effect in an early epidemic phase in Tuscany, and thus limited the transmission of SARS-CoV-2 infection, as well as influenza, in the territory. In March and April, by causing the death of vulnerable elderly patients who had been spared by the mild seasonal flu in the prior months, COVID-19 acted with a harvesting effect.

The COVID-19 lockdowns: a window into the Earth System

The COVID-19 pandemic has caused substantial global impact. This Perspective provides insight into the environmental effects of the pandemic, documenting how it offers an opportunity to better understand the Earth System. Restrictions to reduce human interaction have helped to avoid greater suffering and death from the COVID-19 pandemic, but have also created socioeconomic hardship. This disruption is unprecedented in the modern era of global observing networks, pervasive sensing and large-scale tracking of human mobility and behaviour, creating a unique test bed for understanding the Earth System. In this Perspective, we hypothesize the immediate and long-term Earth System responses to COVID-19 along two multidisciplinary cascades: energy, emissions, climate and air quality;and poverty, globalization, food and biodiversity. While short-term impacts are dominated by direct effects arising from reduced human activity, longer-lasting impacts are likely to result from cascading effects of the economic recession on global poverty, green investment and human behaviour. These impacts offer the opportunity for novel insight, particularly with the careful deployment of targeted data collection, coordinated model experiments and solution-oriented randomized controlled trials, during and after the pandemic.

A Web Survey to Evaluate the Thermal Stress Associated with Personal Protective Equipment among Healthcare Workers during the COVID-19 Pandemic in Italy

The pandemic has been afflicting the planet for over a year and from the occupational point of view, healthcare workers have recorded a substantial increase in working hours. The use of personal protective equipment (PPE), necessary to keep safe from COVID-19 increases the chances of overheating, especially during the summer seasons which, due to climate change, are becoming increasingly warm and prolonged. A web survey was carried out in Italy within the WORKLIMATE project during the summer and early autumn 2020. Analysis of variance (ANOVA) was used to evaluate differences between groups. 191 questionnaires were collected (hospital doctor 38.2%, nurses 33.5%, other healthcare professionals 28.3%). The impact of PPE on the thermal stress perception declared by the interviewees was very high on the body areas directly covered by these devices (78% of workers). Workers who used masks for more than 4 h per day perceived PPE as more uncomfortable (p < 0.001) compared to the others and reported a greater productivity loss (p < 0.001). Furthermore, the study highlighted a high perception of thermal stress among healthcare workers that worn COVID-19-PPE and this enhances the need for appropriate heat health warning systems and response measures addressed to the occupational sector.

Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection;b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.