Is Ozone therapy an adjunct treatment for SARS-CoV-2 / COVID-19 infection?

Abstract Up to today, there is no specific treatment against SARS-CoV-2 / COVID-19 infection; there the necessity to search for alternatives that help patients with COVID-19. The objective of this study was to review the use of ozone therapy as adjunct treatment for SARS-CoV-2 / COVID-19 infection, highlighting the mechanisms of action, forms of application and current clinical evidence. A systematic review was conducted in electronic databases, searching the terminology Ozone "or" Ozone therapy "and" SARS-CoV-2 or COVID-19 or Coronavirus. Results: nineteen studies were included; ten were editorials, comments, brief reports or reviews, and nine clinical studies. We found that ozone therapy could be favorable for treating patients infected with SARS-CoV-2 / COVID-19, through a direct antiviral effect, regulation of oxidative stress, immunomodulation and improvement of oxygen metabolism. Patients who were treated with ozone therapy responded favorably; therefore, ozone therapy appears to be a promising treatment for patients infected with SARS-CoV-2 / COVID-19. Its mechanism of action justifies its use as an adjuvant therapy; however, scientific evidence is based on case series and clinical trials are necessary to corroborate its effectiveness and safety.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Clinical study reports published by the European Medicines Agency 2016-2018: a cross-sectional analysis.

OBJECTIVES: To describe the characteristics of clinical study report (CSR) documents published by the European Medicines Agency (EMA), and for included pivotal trials, to quantify the timeliness of access to trial results from CSRs compared with conventional published sources. DESIGN: Cross-sectional analysis of CSR documents published by the EMA from 2016 to 2018. METHODS: CSR files and medication summary information were downloaded from the EMA. Individual trials in each submission were identified using document filenames. Number and length of documents and trials were determined. For pivotal trials, trial phase, dates of EMA document publication and matched journal and registry publications were obtained. RESULTS: The EMA published documents on 142 medications that were submitted for regulatory drug approval. Submissions were for initial marketing authorisations in 64.1%. There was a median of 15 (IQR 5-46) documents, 5 (IQR 2-14) trials and 9629 (IQR 2711-26,673) pages per submission, and a median of 1 (IQR 1-4) document and 336 (IQR 21-1192) pages per trial. Of all identified pivotal trials, 60.9% were phase 3 and 18.5% were phase 1. Of 119 unique submissions to the EMA, 46.2% were supported by a single pivotal trial, with 13.4% based on a single pivotal phase 1 trial. No trial registry results were identified for 26.1% trials, no journal publications for 16.7% and 13.5% of trials had neither. EMA publication was the earliest information source for 5.8% of pivotal trials, available a median 523 days (IQR 363-882 days) before the earliest publication. CONCLUSIONS: The EMA Clinical Data website contains lengthy clinical trial documents. Almost half of submissions to the EMA were based on single pivotal trials, many of which were phase 1 trials. CSRs were the only source and a timelier source of information for many trials. Access to unpublished trial information should be open and timely to support decision-making for patients.

Research Report: Exploring Needs, Impediments and Perspectives for a Digital Mental Health Tool in Psychiatric Settings.

The COVID-19 pandemic brought forth rapid responses and changes in the acceptance of digital health interventions. Digital solutions appear increasingly promising, yet little is known about the peculiarities in the psychiatric context, contrary to other medical branches. The project MeHealth aimed at disclosing specific needs and reservations of patients and professionals in the psychiatric field. Apprehensions towards technology were found to be held on both sides. Cooperating with a psychiatric hospital in Austria, through a transdisciplinary research approach including focus groups and workshops, a framework for an integrated Digital Mental Health Tool was established. The findings leading to the framework show a strong need for patient-empowerment, enhancement of trust in technology and the need for multi-stakeholder cooperation. Digital tools should be designed to enhance the continuity of care and information exchange on behalf of the patient. Learnings were gained, which prove recommendable for future R&D projects on digitalization in the delicate field of psychiatry.

Brief Research Report: Serum clara cell 16 kDa protein levels are increased in patients hospitalized for severe SARS-CoV-2 or sepsis infection.

Background: Clara cell 16 kDa protein (CC16) is a secretory protein primarily expressed in epithelial cells in the lungs. Previous studies show that CC16 exerts anti-inflammatory and immune-modulatory properties in both acute and chronic pulmonary diseases. However, despite the evidence of CC16's high biomarker potential, evaluation of its role in infectious diseases is yet very limited. Methods: Serum CC16 concentrations were measured by ELISA and assessed in two different types of severe infections. Using a case-control study design, patients treated for either severe SARS-CoV-2 or severe non-pulmonary sepsis infection were compared to age- and sex-matched healthy human subjects. Results: Serum CC16 was significantly increased in both types of infection (SARS-CoV-2: 96.22 ± 129.01 ng/ml vs. healthy controls: 14.05 ± 7.48 ng/ml, p = 0.022; sepsis: 35.37 ± 28.10 ng/ml vs. healthy controls: 15.25 ± 7.51 ng/ml, p = 0.032) but there were no distinct differences between infections with and without pulmonary focus (p = 0.089). Furthermore, CC16 serum levels were positively correlated to disease duration and inversely to the platelet count in severe SARS-CoV-2 infection. Conclusions: Increased CC16 serum levels in both SARS-CoV-2 and sepsis reinforce the high potential as a biomarker for epithelial cell damage and bronchoalveolar-blood barrier leakage in pulmonary as well as non-pulmonary infectious diseases.

[Integrated Surveillance in Italy: outputs and related activities]. / La sorveglianza integrata COVID-19 in Italia: output e attività correlate.

OBJECTIVES: to describe the integrated surveillance system of COVID-19 in Italy, to illustrate the outputs used to return epidemiological information on the spread of the epidemic to the competent public health bodies and to the Italian population, and to describe how the surveillance data contributes to the ongoing weekly regional monitoring and risk assessment system. METHODS: the COVID-19 integrated surveillance system is the result of a close and continuous collaboration between the Italian National Institute of Health (ISS), the Italian Ministry of Health, and the regional and local health authorities. Through a web platform, it collects individual data of laboratory confirmed cases of SARS-CoV-2 infection and gathers information on their residence, laboratory diagnosis, hospitalisation, clinical status, risk factors, and outcome. Results, for different levels of aggregation and risk categories, are published daily and weekly on the ISS website, and made available to national and regional public health authorities; these results contribute one of the information sources of the regional monitoring and risk assessment system. RESULTS: the COVID-19 integrated surveillance system monitors the space-time distribution of cases and their characteristics. Indicators used in the weekly regional monitoring and risk assessment system include process indicators on completeness and results indicators on weekly trends of newly diagnosed cases per Region. CONCLUSIONS: the outputs of the integrated surveillance system for COVID-19 provide timely information to health authorities and to the general population on the evolution of the epidemic in Italy. They also contribute to the continuous re-assessment of risk related to transmission and impact of the epidemic thus contributing to the management of COVID-19 in Italy.

Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.

We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (published January 2020) or were characterized earlier but have since been confirmed or expanded in subsequent studies. While variants in additional genes associated with immune diseases have been reported in the literature, this update includes only those that the committee assessed that reached the necessary threshold to represent novel inborn errors of immunity. There are now a total of 485 inborn errors of immunity. These advances in discovering the genetic causes of human immune diseases continue to significantly further our understanding of molecular, cellular, and immunological mechanisms of disease pathogenesis, thereby simultaneously enhancing immunological knowledge and improving patient diagnosis and management. This report is designed to serve as a resource for immunologists and geneticists pursuing the molecular diagnosis of individuals with heritable immunological disorders and for the scientific dissection of cellular and molecular mechanisms underlying monogenic and related human immune diseases.

The methodological quality of economic evaluations of measles outbreaks: A systematic review of cost-of-illness studies.

OBJECTIVES: To identify the main cost components included in the economic evaluations of measles outbreaks, their items and cost drivers, and evaluate the quality of costing methodology, analyzing the key features that may affect the validity of these studies in countries with different income levels. METHODS: We systematically searched multiple databases EMBASE, MEDLINE (via PubMed), Biblioteca Virtual em Saúde do Ministério da Saúde (BVS MS), NHS Economic Evaluation Database (NHS EED) and NHS Health Technology Assessment (NHS HTA) (via The Centre for Reviews and Dissemination Library - CRD), and EconLit, SCOPUS, and Web of Science, selecting cost analysis and cost of illness studies (COI) of measles outbreaks. Two independent reviewers screened articles for relevance and extracted the data. The quality of costing methods was assessed using a guide to critical evaluation of COI studies. We performed a qualitative narrative synthesis. RESULTS: Twenty-two studies were reviewed. Most studies evaluated outbreaks that occurred from 2011 to 2013 and 2017 to 2019. Total costs varied from $40,147 to $39.3 million. Per case cost varied from $168 to $49,439. The main drivers of measles outbreak costs were outbreak response, personnel, and productivity losses. Most studies (20/22) did not report the costing methodology adopted, the degree of disaggregation used in the identification and measurement of resource and costs components and the method for the valuation of resource and cost components. CONCLUSIONS: The quality of the costing methodology, its transparency and accuracy are essential to the validity of these studies results and their potential use to allocate public health resources in the most efficient manner and to inform measles outbreak control strategies, with rapid and effective response.

Brief Research Report: Anti-SARS-CoV-2 Immunity in Long Lasting Responders to Cancer Immunotherapy Through mRNA-Based COVID-19 Vaccination.

Cancer patients (CPs) have been identified as particularly vulnerable to SARS-CoV-2 infection, and therefore are a priority group for receiving COVID-19 vaccination. From the patients with advanced solid tumors, about 20% respond very efficiently to immunotherapy with anti-PD1/PD-L1 antibodies and achieve long lasting cancer responses. It is unclear whether an efficient cancer-specific immune response may also correlate with an efficient response upon COVID-19 vaccination. Here, we explored the antiviral immune response to the mRNA-based COVID-19 vaccine BNT162b2 in a group of 11 long-lasting cancer immunotherapy responders. We analysed the development of SARS-CoV-2-specific IgG serum antibodies, virus neutralizing capacities and T cell responses. Control groups included patients treated with adjuvant cancer immunotherapy (IMT, cohort B), CPs not treated with immunotherapy (no-IMT, cohort C) and healthy controls (cohort A). The median ELISA IgG titers significantly increased after the prime-boost COVID vaccine regimen in all cohorts (Cohort A: pre-vaccine = 900 (100-2700), 3 weeks (w) post-boost = 24300 (2700-72900); Cohort B: pre-vaccine = 300 (100-2700), 3 w post-boost = 8100 (300-72900); Cohort C: pre-vaccine = 500 (100-2700), 3 w post-boost = 24300 (300-72900)). However, at the 3 w post-prime time-point, only the healthy control group showed a statistically significant increase in antibody levels (Cohort A = 8100 (900-8100); Cohort B = 900 (300-8100); Cohort C = 900 (300-8100)) (P < 0.05). Strikingly, while all healthy controls generated high-level antibody responses after the complete prime-boost regimen (Cohort A = 15/15 (100%), not all CPs behaved alike [Cohort B= 12/14 (84'6%); Cohort C= 5/6 (83%)]. Their responses, including those of the long-lasting immunotherapy responders, were more variable (Cohort A: 3 w post-boost (median nAb titers = 95.32 (84.09-96.93), median Spike-specific IFN-γ response = 64 (24-150); Cohort B: 3 w post-boost (median nAb titers = 85.62 (8.22-97.19), median Spike-specific IFN-γ response (28 (1-372); Cohort C: 3 w post-boost (median nAb titers = 95.87 (11.8-97.3), median Spike-specific IFN-γ response = 67 (20-84)). Two long-lasting cancer responders did not respond properly to the prime-boost vaccination and did not generate S-specific IgGs, neutralizing antibodies or virus-specific T cells, although their cancer immune control persisted for years. Thus, although mRNA-based vaccines can induce both antibody and T cell responses in CPs, the immune response to COVID vaccination is independent of the capacity to develop an efficient anti-cancer immune response to anti PD-1/PD-L1 antibodies.

Global Matrix 4.0 Physical Activity Report Card Grades for Children and Adolescents: Results and Analyses From 57 Countries.

BACKGROUND: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children's and adolescents' (5-17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. METHODS: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders' top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. RESULTS: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. CONCLUSIONS: The Global Matrix 4.0 represents the largest compilation of children's and adolescents' PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

The natural language processing of radiology requests and reports of chest imaging: Comparing five transformer models' multilabel classification and a proof-of-concept study.

BACKGROUND: Radiology requests and reports contain valuable information about diagnostic findings and indications, and transformer-based language models are promising for more accurate text classification. METHODS: In a retrospective study, 2256 radiologist-annotated radiology requests (8 classes) and reports (10 classes) were divided into training and testing datasets (90% and 10%, respectively) and used to train 32 models. Performance metrics were compared by model type (LSTM, Bertje, RobBERT, BERT-clinical, BERT-multilingual, BERT-base), text length, data prevalence, and training strategy. The best models were used to predict the remaining 40,873 cases' categories of the datasets of requests and reports. RESULTS: The RobBERT model performed the best after 4000 training iterations, resulting in AUC values ranging from 0.808 [95% CI (0.757-0.859)] to 0.976 [95% CI (0.956-0.996)] for the requests and 0.746 [95% CI (0.689-0.802)] to 1.0 [95% CI (1.0-1.0)] for the reports. The AUC for the classification of normal reports was 0.95 [95% CI (0.922-0.979)]. The predicted data demonstrated variability of both diagnostic yield for various request classes and request patterns related to COVID-19 hospital admission data. CONCLUSION: Transformer-based natural language processing is feasible for the multilabel classification of chest imaging request and report items. Diagnostic yield varies with the information in the requests.