BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease, hypertension and type 2 diabetes mellitus. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis, selecting controls who had not developed sepsis despite having maximum co-morbidity risk and exposure to sepsis-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.

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The heterogeneous and multi-factorial nature of dementia requires the consideration of all health aspects when predicting the risk of its development and planning strategies for its prevention. This systematic review of reviews provides a comprehensive synthesis of those factors associated with cognition in the context of dementia, identifying the role of social aspects and evidencing knowledge gaps in this area of research. Systematic reviews and meta-analyses from 2009–2021 were searched for within Medline, PsycINFO, CINAHL Complete, Cochrane, and Epistemonikos. Reviewers independently screened, reviewed, and assessed the records, following the PRISMA-2020 guidelines. From 314 included studies, 624 cognitive-related factors were identified, most of them risk factors (61.2%), mainly belonging to the group of ‘somatic comorbidities’ (cardiovascular disease and diabetes) and ‘genetic predispositions’. The protective factors (20%) were mainly related to lifestyle, pointing to the Mediterranean diet, regular physical activity, and cognitively stimulating activities. Social factors constituted 9.6% of all identified factors. Research on biological and medical factors dominates the reviewed literature. Greater social support and frequent contact may confer some protection against cognitive decline and dementia by delaying its onset or reducing the overall risk; however, overall, our findings are inconsistent. Further research is needed in the fields of lifestyle, psychology, social health, and the protective factors against cognitive decline and dementia.

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Background Dementia is a multi-factorial condition rather than a natural and inevitable consequence of ageing. Some factors related to dementia have been studied much more extensively than others. To gain an overview of known or suspected influential factors is a prerequisite to design studies that aim to identify causal relationships and interactions between factors. This article aims to develop a visual model that a) identifies factors related to cognitive decline that signal the onset of dementia, b) structures them by different domains and c) reflects on and visualizes the possible causal links and interactions between these factors based on expert input using a causal loop diagram. Method We used a mixed-method, step-wise approach: 1. A systematic literature review on factors related to cognitive decline; 2. A group model building (GMB) workshop with experts from different disciplines; 3. Structured discussions within the group of researchers. The results were continuously synthesized and graphically transformed into a causal loop diagram. Results The causal loop diagram comprises 73 factors that were structured into six domains: physical (medical) factors (23), social health factors (21), psychological factors (14), environmental factors (5), demographic factors (5) and lifestyle factors (3). 57 factors were identified in the systematic literature review, additionally 16 factors, mostly of the social health cluster, were identified during the GMB session and the feedback rounds. Conclusion The causal loop diagram offers a comprehensive visualisation of factors related to cognitive decline and their interactions. It supports the generation of hypotheses on causal relationships and interactions of factors within and between domains.

People with multiple sclerosis (MS) were expected to be particularly affected by the COVID-19 pandemic. The purpose of the study was to evaluate the burden of pandemic, perceived by Polish MS patients, with regard to major contributing factors. The survey, conducted in August/September 2020, included: Perceived Stress Scale (PSS-10), Coping Orientations to Problems Experienced (Brief–COPE), questions on demographic data, MS characteristics, and health-related and social aspects of pandemic burden. Relationships were searched between PSS-10 and Mini-COPE results and other analyzed items, using U Mann–Whitney test, Kruskal–Wallis ANOVA rank test and Spearman rank correlation. The survey was answered by 287 MS patients (208 female, 79 male, aged 21–69 years). Since March 2020, 2.4% of respondents had been positive for COVID-19 and 5.2% had undergone a quarantine. Mean PSS-10 score was 19.99, with moderate or high level of stress in 83.3% of respondents. Problem-focused strategies were more frequently used than emotion-focused strategies (1.76 vs. 1.16). Higher PSS-10 score was associated with comorbidities (H = 4.28), increase in major MS symptoms during the pandemic (21.92 vs. 18.06), experience of healthcare limitations (21.12 vs. 17.98), work-related (22.58 vs. 18.69), financial (22.70 vs. 18.83) and family-related problems (22.54 vs. 17.73) due to pandemic restrictions. A coping model was associated with functional disability and limitations to daily activities (H = 7.81). During the first stage of the pandemic, MS patients reported increased level of stress and preferred problem-focused coping. The level of stress and coping showed more relationships with pandemic impact upon social issues than with MS-related variables.

Rozlany uraz aksonalny (ang. diffuse axonal injury- DAI) jest mikroskopowym uszkodzeniem aksonów biegnących w mózgu. Do jego wystąpienia predysponują urazy głowy z przyśpieszeniem lub zahamowaniem. W niniejszym artykule zaprezentowano aktualny stan wiedzy na temat DAI oraz przypadki dwóch pacjentów, u których DAI wystąpiło w wyniku wypadku komunikacyjnego. U 26- letniego mężczyzny po dachowaniu pojazdu stwierdzono w TK cechy obrzmienia mózgowia oraz rozsiane drobne wybroczyny hyperdensyjnej krwi. Konsultacja psychiatryczna w 9 dobie wykazała między innymi zaburzenia pamięci w postaci niepamięci wstecznej i następczej, zaburzenia koncentracji oraz brak krytycyzmu wobec swojego stanu. U 38- letniej kobiety potrąconej przez samochód opisano w TK głowy cechy obrzmienia mózgowia, niewielkiego krwawienia podpajęczynówkowego oraz liczne złamania. Pacjentka w 10 dobie zdezorientowana, nie zapamiętywała udzielanych informacji, we wzmożonym napędzie i brakiem krytycyzmu wobec stanu zdrowia. Podejrzewając DAI powinniśmy zachować szczególną czujność w przypadku pacjentów hospitalizowanych z powodu wypadków komunikacyjnych z zaburzeniami zachowania, cechami zespołu amnestycznego oraz bez istotnych ogniskowych objawów neurologicznych.

BACKGROUNDCoronavirus disease 2019 (COVID-19) is a novel coronavirus strain disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease is highly transmissible and severe disease including viral sepsis has been reported in up to 16% of hospitalized cases. The admission characteristics associated with increased odds of hospital mortality among confirmed cases of COVID-19 include severe hypoxia, low platelet count, elevated bilirubin, hypoalbuminemia and reduced glomerular filtration rate. These symptoms correlate highly with severe sepsis cases. The diseases also share similar comorbidity risks including dementia, type 2 diabetes mellitus, coronary heart disease, hypertension and chronic renal failure. Sepsis has been observed in up to 59% of hospitalized COVID-19 patients.It is highly desirable to identify risk factors and novel therapy/drug repurposing avenues for late-stage severe COVID-19 patients. This would enable better protection of at-risk populations and clinical stratification of COVID-19 patients according to their risk for developing life threatening disease. METHODSAs there is currently insufficient data available for confirmed COVID-19 patients correlating their genomic profile, disease severity and outcome, co-morbidities and treatments as well as epidemiological risk factors (such as ethnicity, blood group, smoking, BMI etc.), a direct study of the impact of host genomics on disease severity and outcomes is not yet possible. We therefore ran a study on the UK Biobank sepsis cohort as a surrogate to identify sepsis associated signatures and genes, and correlated these with COVID-19 patients.Sepsis is itself a life-threatening inflammatory health condition with a mortality rate of approximately 20%. Like the initial studies for COVID-19 patients, standard genome wide association studies (GWAS) have previously failed to identify more than a handful of genetic variants that predispose individuals to developing sepsis. RESULTSWe used a combinatorial association approach to analyze a sepsis population derived from UK Biobank. We identified 70 sepsis risk-associated genes, which provide insights into the disease mechanisms underlying sepsis pathogenesis. Many of these targets can be grouped by common mechanisms of action such as endothelial cell dysfunction, PI3K/mTOR pathway signaling, immune response regulation, aberrant GABA and neurogenic signaling. CONCLUSIONThis study has identified 70 sepsis related genes, many of them for the first time, that can reasonably be considered to be potentially relevant to severe COVID-19 patients. We have further identified 59 drug repurposing candidates for 13 of these targets that can be used for the development of novel therapeutic strategies to increase the survival rate of patients who develop sepsis and potentially severe COVID-19.