Mind the gap: Data availability, accessibility, transparency, and credibility during the COVID-19 pandemic, an international comparative appraisal.

Data transparency has played a key role in this pandemic. The aim of this paper is to map COVID-19 data availability and accessibility, and to rate their transparency and credibility in selected countries, by the source of information. This is used to identify knowledge gaps, and to analyse policy implications. The availability of a number of COVID-19 metrics (incidence, mortality, number of people tested, test positive rate, number of patients hospitalised, number of patients discharged, the proportion of population who received at least one vaccine, the proportion of population fully vaccinated) was ascertained from selected countries for the full population, and for few of stratification variables (age, sex, ethnicity, socio-economic status) and subgroups (residents in nursing homes, inmates, students, healthcare and social workers, and residents in refugee camps). Nine countries were included: Bangladesh, Indonesia, Iran, Nigeria, Turkey, Panama, Greece, the UK, and the Netherlands. All countries reported periodically most of COVID-19 metrics on the total population. Data were more frequently broken down by age, sex, and region than by ethnic group or socio-economic status. Data on COVID-19 is partially available for special groups. This exercise highlighted the importance of a transparent and detailed reporting of COVID-19 related variables. The more data is publicly available the more transparency, accountability, and democratisation of the research process is enabled, allowing a sound evidence-based analysis of the consequences of health policies.

Increased Gal-3BP plasma levels in hospitalized patients infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has quickly turned into a health, financial and societal problem globally. The complex pathogenesis of severe acute respiratory syndrome coronavirus centers on the unpredictable clinical progression of the disease, which may evolve abruptly and results in critical and life-threatening clinical complications. Effective laboratory biomarkers that can classify patients according to risk of progression to severe disease are essential for ensuring timely treatment. Gal-3BP is a human secreted protein with innate immune functions, which is upregulated in viral infections, promotes inflammation and has been shown to induce IL-6 expression. In this study, Gal-3BP plasma levels were measured retrospectively in a cohort of 84 hospitalized COVID-19 patients. These were classified as having either "non-severe" or "severe" disease. Compared to healthy controls, Gal-3BP plasma levels were markedly increased in COVID-19 patients (P < 0.0001). Moreover, the levels were higher in severe than in non-severe patients (P < 0.05). As expected, patients with severe disease had plasma levels of IL-6 higher than patients with non-severe disease (P < 0.01). In non-severe disease patients, Gal-3BP levels collected at a late stage (13.3 + 5.7 days after the first positive PCR result) were significantly lower than those collected at an early stage (4.2 + 2.9 days form the first positive PCR result). Larger prospective analyses are needed to strength our understanding of the prognostic utility of Gal-3BP in COVID-19 patients.

The timelines for the price and reimbursement authorization in Italy 2018-2020.

Objective: This investigation aimed to guarantee the principles of transparency in public administration; to inform citizens about the time to patient access to reimbursed medicines; to assess the duration of the P&R process for the first time in the period 2018-2020; and to evaluate whether and how the SARS-CoV-2 (COVID-19) pandemic affected the P&R activity. This study analyzed the timelines of pricing and reimbursement procedures submitted in Italy by the pharmaceutical marketing authorization holder (MAH) from 2018 to 2020. Methods: The analysis was run through an AIFA web-based platform that collects data about P&R procedures for each step of the Italian Price and Reimbursement (P&R) procedure, including dates of the Technical Scientific Committee (CTS) and Price and Reimbursement Committee (CPR) meetings from January 2018 to December 2020. On this basis, four indicators were developed relating to the completion time of each stage of the P&R negotiation process and were defined in terms of days. In this regard, descriptive analyses, graphical boxplots, and survival curves (Kaplan-Meier) were carried out, studying these indicators in relation to the typology of pharmaceutical procedures. Results: Overall, in the period 2018-2020, 57.1% of the 2,445 procedures entered were represented by the Off-patent pharmaceuticals procedures (generics, biosimilars, copies, and/or parallel trade). In 2020, the overall process duration for Off-patent pharmaceuticals procedures was equal to 129.8 average days [95% CI: (122.3-137.2)], with a median value of 108.0, whereas for In-patent pharmaceuticals procedures, it was equal to 283.1 average days [95% CI: (267.8-298.5)], with a median value of 284.0. Over time, the trend of the entire duration of the P&R process tended to decrease. In terms of estimated timing for the conclusion of each stage of the P&R negotiation process, the difference between Off-patent and In-patent pharmaceutical procedures was statistically significant by the Log-Rank test. Discussion and conclusion: This is the first study to examine the time of the P&R process in Italy, from MAH submission to the publication of the final decision in the Italian Official Journal. The time span considered is 3 years, including the first year of the COVID-19 pandemic. Compared to European average times, in Italy, the time necessary for evaluation, authorization for reimbursement, and definition of the price of a medicine can be considered satisfactory.

Galectin-3 binding protein stimulated IL-6 expression is impeded by antibody intervention in SARS-CoV-2 susceptible cell lines.

COVID-19 is the global pandemic that affected our population in the past 2 years. Considerable research has been done to better understand the pathophysiology of this disease and to identify new therapeutic targets, especially for severe cases. Galectin-3 (Gal-3) is a receptor present at the surface of different cell types, namely epithelial and inflammatory cells, which has been described as a severity marker in COVID-19. The activation of Gal-3 through its binding protein (Gal-3BP) is directly linked to the production of pro-inflammatory cytokines that contribute for the cytokine storm (CS) observed in severe COVID-19 patients. Here, we show that D2, a recombinant fragment of the lectin-binding region of Gal-3BP was able to stimulate the expression of IL-6 in colon and lung epithelial cell lines in ß-galactoside dependent manner. We further show that D2-induced IL-6 augmentation was reduced by the anti-Gal-3BP monoclonal antibody 1959. Our data confirm and extend prior findings of Gal-3BP mediated IL-6 induction, enlightening the potential of its antibody-mediated s blockage for the prevention and treatment of CS and severe disease in COVID-19 patients.

Gal-3BP in Viral Infections: An Emerging Role in Severe Acute Respiratory Syndrome Coronavirus 2.

Galectin-3 binding protein (Gal-3BP) is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV, and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP's complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of interferons (IFNs) and proinflammatory cytokines, including interleukin-6 (IL-6), mainly interacting with galectin-3, targeting the TNF receptor-associated factors (TRAF-6 and TRAF-3) complex, thus having a putative role in the modulation of TGF-ß signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP's role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.

Antiviral properties of whey proteins and their activity against SARS-CoV-2 infection.

Native and chemically modified whey proteins and their peptide derivatives are encountering the interest of nutraceutical and pharmaceutical industries, due to the numerous properties, ranging from antimicrobial to immunological and antitumorigenic, that result in the possibility to employ milk and its protein components in a wide range of treatment and prevention strategies. Importantly, whey proteins were found to exert antiviral actions against different enveloped and non-enveloped viruses. Recently, the scientific community is focusing on these proteins, especially lactoferrin, since in vitro studies have demonstrated that they exert an important antiviral activity also against SARS-CoV-2. Up-to date, several studies are investigating the efficacy of lactoferrin and other whey proteins in vivo. Aim of this review is to shed light on the most relevant findings concerning the antiviral properties of whey proteins and their potential applications in human health, focussing on their application in prevention and treatment of SARS-CoV-2 infection.

Comparing the COVID-19 pandemic in space and over time in Europe, using numbers of deaths, crude rates and adjusted mortality trend ratios.

Comparison of COVID-19 trends in space and over time is essential to monitor the pandemic and to indirectly evaluate non-pharmacological policies aimed at reducing the burden of disease. Given the specific age- and sex- distribution of COVID-19 mortality, the underlying sex- and age-distribution of populations need to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID-19 using adjusted mortality trend ratios (AMTRs). Age- and sex-mortality distribution of a reference European population (N = 14,086) was used to calculate age- and sex-specific mortality rates. These were applied to each country to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries on a daily basis from 17th March 2020 to 29th April 2021 by dividing observed cumulative mortality, by expected mortality, times the crude mortality of the reference population. These estimated the sex- and age-adjusted mortality for COVID-19 per million population in each country. United Kingdom experienced the highest number of COVID-19 related death in Europe. Crude mortality rates were highest Hungary, Czech Republic, and Luxembourg. Accounting for the age-and sex-distribution of the underlying populations with AMTRs for each European country, four different patterns were identified: countries which experienced a two-wave pandemic, countries with almost undetectable first wave, but with either a fast or a slow increase of mortality during the second wave; countries with consistently low rates throughout the period. AMTRs were highest in Eastern European countries (Hungary, Czech Republic, Slovakia, and Poland). Our methods allow a fair comparison of mortality in space and over time. These might be of use to indirectly estimating the efficacy of non-pharmacological health policies. The authors urge the World Health Organisation, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID-19 pandemic worldwide.

Launching of the Anaemia Research Peruvian Cohort (ARPEC): a multicentre birth cohort project to explore the iron adaptive homeostasis, infant growth and development in three Peruvian regions.

BACKGROUND: Preventing infantile anaemia and ensuring optimal growth and development during early childhood, particularly in resource-constrained settings, represent an ongoing public health challenge. Current responses are aligned to treatment-based solutions, instead of determining the roles of its inter-related causes. This project aims to assess and understand the complex interplay of eco-bio-social-political factors that determine infantile anaemia to inform policy, research design and prevention practices. METHODS: This is a longitudinal birth cohort study including four components: (1) biological, will assess known blood markers of iron homeostasis and anaemia and stool microbiota to identify and genetically analyse the participants' flora; (2) ecological, will assess and map pollutants in air, water and soil and evaluate features of nutrition and perceived food security; (3) social, which will use different qualitative research methodologies to explore key stakeholders and informants' perceptions related to nutritional, environmental and anaemia topics, participant observations and a participatory approach and (4) a political analysis, to identify and assess the impact of policies, guidelines and programmes at all levels for infantile anaemia in the three regions. Finally, we will also explore the role of social determinants and demographic variables longitudinally for all study participants. This project aims to contribute to the evidence of the inter-related causal factors of infantile anaemia, addressing the complexity of influencing factors from diverse methodological angles. We will assess infantile anaemia in three regions of Peru, including newborns and their mothers as participants, from childbirth until their first year of age. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Research Ethics Committee of the Instituto Nacional de Salud del Niño (Lima, Peru), CIEI-043-2019. An additional opinion has been granted by the Ethical Committee of Queen Mary University of London (London, UK). Dissemination across stakeholders is taking part as a continues part of the research process.

Feasibility study of assessing the Preclinical Alzheimer Cognitive Composite (PACC) score via videoconferencing.

BACKGROUND: The Preclinical Alzheimer Cognitive Composite (PACC) is a composite score which can detect the first signs of cognitive impairment, which can be of importance for research and clinical practice. It is designed to be administered in person; however, in-person assessments are costly, and are difficult during the current COVID-19 pandemic. OBJECTIVE: To assess the feasibility of performing the PACC assessment with videoconferencing, and to compare the validity of this remote PACC with the in-person PACC obtained previously. METHODS: Participants from the HEalth and Ageing Data IN the Game of football (HEADING) Study who had already undergone an in-person assessment were re-contacted and re-assessed remotely. The correlation between the two PACC scores was estimated. The difference between the two PACC scores was calculated and used in multiple linear regression to assess which variables were associated with a difference in PACC scores. FINDINGS: Of the 43 participants who were invited to this external study, 28 were re-assessed. The median duration in days between the in-person and the remote assessments was 236.5 days (7.9 months) (IQR 62.5). There was a strong positive correlation between the two assessments for the PACC score, with a Pearson correlation coefficient of 0·82 (95% CI 0·66, 0·98). The multiple linear regression found that the only predictor of the PACC difference was the time between assessments. INTERPRETATION: This study provides evidence on the feasibility of performing cognitive tests online, with the PACC tests being successfully administered through videoconferencing. This is relevant, especially during times when face-to-face assessments cannot be performed.