Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease Associated Coronary Arteritis (preprint)

Background and Aim Coronary involvement in Kawasaki Disease (KD), whether its after SARS-CoV2 infection or not, can result in significant complications. There is the risk of aneurysm formation associated with inflammation and an unremitting fever. We wished to study the Vasoactive Endothelial Growth Factor (VEGF) and Heat Shock Response from a gene-expression perspective. Thereby aiming to furnish to insights that might be useful in the treatment of Kawasaki Disease. Method KD datasets based on previous work, were selected including microarray studies KD1 (GSE63881), KD2 (GSE73461), KD3 (GSE68004) and the RNAseq dataset KD4 (GSE64486) from the NCBI online repository. Based on clinical literature. HSP genes shown to be associated with angiogenesis were chosen for analysis as well as gene expression for VEFGA and VEGFB. Further in order to gain an impression of inflammatory patterns, gene expression for NFKB1 and TNF were also chosen. Tools for analysis included Gene Set Expression Analysis (GSEA). A KEGG pathway, outlining a relationship between VEGF and endothelial migration and proliferation was assumed. Results A KD dataset showed increased VEGFA and decreased VEGFB in acute versus convalescent samples. In all three KD datasets, HSPA1A and HSBAP1 genes were upregulated in acute versus convalescent samples. In KD4, cases of KD versus controls, VEGFB was down-regulated (p = 4.932e-02) and HSPBAP1 up-regulated (p = 1.202e-03). GSEA of KD1, KD2 and KD3, using Hallmark gene sets, suggested an inflammatory response with TNFA signaling via NFKB, IL6 JAK STAT 3 signaling, apoptosis, angiogenesis, and unfolded protein response. Conclusions A novel application of a model of VEGF and HSP to KD was presented. Coronary pathogenesis based on VEGF and HSP was explored. The ability to follow angiogenesis at the molecular level using a VEGF-HSP model may have therapeutic implications. Further, the significance of gene expression between VEGFA, VEGFB in KD and the relationship of HSP gene expression to angiogenesis in KD requires further study.

No evidence to support the effectiveness of surgical masks compared to respirators in reducing the risk of COVID-19 infection when providing non-aerosol generating care to COVID-19 patients -- A systematic review (preprint)

We systematically assessed the evidence comparing surgical facemasks to respirators in the prevention of COVID-19 in HCW providing non AGP care in a hospital setting. We identified only one relevant study which reported no significant difference in COVID-19 infection rates amongst HCWs wearing surgical facemasks or FFP1 face-covers as compared to FFP2 respirators. This was an observational study with substantial methodological deficiencies and highlights the need for high quality evidence. However, until this evidence is available, and given that inadequate mask use may increase the risk of nosocomial infection amongst patients and HCWs, we would recommend respirators for non-AGP care.

Global Analysis of SARS-COV-2 Mitigation Impact Reveals an Arabian Peninsula Cluster with High Infection Rates and Shared Indicators (preprint)

Background SARS-CoV-2 is a novel virus that appeared in China in November 2019 and spread rapidly. With no vaccine or effective treatment, countries have adopted different mitigation measures to reduce SARS-COV-2 spread with different efficacy.MethodsWe mapped the impact of mitigation measures across different countries. We compared regional SARS-COV-2 population burden via Kruskal-Wallis statistical testing. We analyzed time of adoption of mitigation measures and the impact of PCR testing on mitigation impact. We analyzed the association of climate, health, demographic and economic indicators with mitigation impact via non-parametric correlation tests. We performed mechanistic modelling of to predict short-term SARS-COV-2 case numbers in selected countries. ResultsMany countries showed a reduction of infection rates within one month of implementing mitigation measures. However, we identified a geographic cluster of countries centered on the Arabian Peninsula (AP) that show a high SARS-COV-2 population burden despite early adoption of mitigation measures. We find that higher air pollution levels (p=0.01), higher CO2 emissions (p=0.03) and younger population (p=0.02) were associated with reduced mitigation impact in AP countries. We also show that mechanistic modelling can closely predict confirmed case numbers in the short term.ConclusionsThe impact of mitigation measures varies greatly between countries. Countries with similar profiles as AP countries should adopt more stringent mitigation measures to more rapidly reduce SARS-CoV-2 spread. Specific interventions targeting young people may also be effective in reducing SARS-COV-2 spread.