Mind The Gap: Data availability, accessibility, transparency, and credibility during the COVID-19 pandemic, an international comparative appraisal (preprint)

Background 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. Methods 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). Results 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. Conclusions 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. Funding This study was conducted as part of the Summer School "Sustainable Health: designing a new, better normal after COVID-19". It is a researchers/student collaboration.

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

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 IFN and pro-inflammatory cytokines, including interleukin-6, mainly interacting with galectin-3, targeting TRAF-6 and TRAF-3 complex, thus having a putative role in the modulation of TGF-β 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 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.

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

COVID-19 is the global pandemic that affected our population in the past two 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 β-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 Levels in Hospitalized Patients Correlate With COVID-19 (preprint)

The ongoing Covid-19 pandemic disease is still lacking effective treatments and relying on a predictive diagnosis for early individuation of patients which will progress to a severe disease can be crucial. To this aim, the search and the identification of new molecular targets of inflammation and disease progression to be used as predictive biomarker of disease severity is important.In this work Gal-3BP was explored as a potential biomarker for COVID-19 severity. We found highly increased circulating levels of Gal-3BP in COVID-19 patients compared to healthy controls. Furthermore, the serum levels of Gal-3BP were higher in those “non severe” patients which progressed to a “severe” disease and correlated with levels of IL-6, a known marker of disease progression in COVID-19 patients. These results suggest that Gal-3BP could be a predictor of Covid-19 severity in early infected patients contributing to extend the panel of the other already known biomarkers associated to Covid-19 severity and progression.

Feasibility Study of Assessing the Preclinical Alzheimer Cognitive Composite (PACC) Score via Videoconferencing (preprint)

Background: Identifying mild cognitive impairment (MCI) at early stages is of importance both for research and for clinical practice. The Preclinical Alzheimer Cognitive Composite (PACC) is a composite score which can detect the first signs of cognitive impairment. It is designed to be administered in person, by a trained research psychologist or nurse, however, in-person assessments are costly, and are difficult during the current COVID-19 pandemic. The aims of this study are to assess the feasibility of performing the PACC assessment with videoconferencing, and to compare the validity of this remote PACC score with the in-person PACC score 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 Spearman correlation coefficient of 0·75 (95% CI 0·56, 0·95). 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 all four tests comprising the PACC being successfully administered through videoconferencing. This is relevant, especially during times when face-to-face assessments cannot be performed.Funding Statement: This study was funded by the Drake Foundation as part of the BRAIN study funded to London School of Hygiene and Tropical Medicine (EPMSZO61) in collaboration with Queen Mary University of London and the Institute of Occupational Health.Declaration of Interests: We declare that we have no conflict of interests. Ethics Approval Statement: The HEADING Study was approved by the London School of Hygiene & Tropical Medicine’s Ethical Committee (16282).

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

Background Since COVID19 was declared a pandemic, attempts have been made to monitor trends over time and to compare countries and regions. Insufficient testing for COVID19 underestimates the incidence and inflates the case/fatality proportion. Given the age and sex distribution of morbidity and mortality from COVID19, the underlying sex and age distribution of a population needs to be accounted for. The aim of this paper is to present a method for monitoring trends of COVID19 using adjusted mortality trend ratios (AMTR). Methods Age and sex mortality distribution of a reference population composed of the first 14,086 fatalities which occurred before the end of March and were reported in Europe by some countries were used to calculate age and sex specific mortality rates per 1,000,000 population. These were applied to each country population to calculate the expected deaths. Adjusted Mortality Trend Ratios (AMTRs) with 95% confidence intervals (C.I.) were calculated for selected European countries from 17/03/2020 to 22/06/2020 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 COVID19 per million population in each country. Results The cumulative mortality from COVID19, the crude mortality rates, and the AMTRs were calculated for each country and compared. United Kingdom, Italy, France and Spain registered the highest mortality in Europe. On 22/06/2020 in Europe the total mortality rate from COVID-19 was 352 per 1,000,000 inhabitants; and it was highest in Belgium (850 per 1,000,000 inhabitants) followed by Spain, UK, Italy, Sweden and France. When accounting for the underlying age and sex structure of each country, Belgium remained the single country experiencing the highest AMTR of 929 per million inhabitants on 22/06/2020; however Ireland (which had a CMR in line with the total European population) emerged as having experienced a much more important impact of COVID19 mortality with an AMTR of 550/million on 22/06/2020, higher than Sweden and Italy. Conclusions In understanding and managing the pandemic of COVID19, comparable international data is a priority. Our methods allow a fair comparison of mortality in space and over time. The authors urge the WHO, given the absence of age and sex-specific mortality data for direct standardisation, to adopt this method to estimate the comparative mortality from COVID19 pandemic worldwide.