Coagulation factors and COVID-19 severity: Mendelian randomization analyses and supporting evidence (preprint)

BackgroundThe evolving pandemic of COVID-19 is arousing alarm to public health. According to epidemiological and observational studies, coagulopathy was frequently seen in severe COVID-19 patients, yet the causality from specific coagulation factors to COVID-19 severity and the underlying mechanism remain elusive. MethodsFirst, we leveraged Mendelian randomization (MR) analyses to assess causal relationship between 12 coagulation factors and severe COVID-19 illness based on two genome-wide association study (GWAS) results of COVID-19 severity. Second, we curated clinical evidence supporting causal associations between COVID-19 severity and particular coagulation factors which showed significant results in MR analyses. Third, we validated our results in an independent cohort from UK Biobank (UKBB) using polygenic risk score (PRS) analysis and logistic regression model. For all MR analyses, GWAS summary-level data were used to ascertain genetic effects on exposures against disease risk. ResultsWe revealed that genetic predisposition to the antigen levels of von Willebrand factor (VWF) and the activity levels of its cleaving protease ADAMTS13 were causally associated with COVID-19 severity, wherein elevated VWF antigen level (P = 0.005, odds ratio (OR) = 1.35, 95% confidence interval (CI): 1.09-1.68 in the Severe COVID-19 GWAS Group cohort; P = 0.039, OR = 1.21, 95% CI: 1.01-1.46 in the COVID-19 Host Genetics Initiative cohort) and lowered ADAMTS13 activity (P = 0.025, OR = 0.69, 95% CI: 0.50-0.96 in the Severe COVID-19 GWAS Group cohort) lead to increased risk of severe COVID-19 illness. No significant causal association of tPA, PAI-1, D-dimer, FVII, PT, FVIII, FXI, aPTT, FX or ETP with COVID-19 severity was observed. In addition, as an independent factor, VWF PRS explains a 31% higher risk of severe COVID-19 illness in the UKBB cohort (P = 0.047, OR per SD increase = 1.31, 95% CI: 1.00-1.71). In combination with age, sex, BMI and several pre-existing disease statues, our model can predict severity risks with an AUC of 0.70. ConclusionTogether with the supporting evidence of recent retrospective cohort studies and independent validation based on UKBB data, our results suggest that the associations between coagulation factors VWF/ADAMTS13 and COVID-19 severity are essentially causal, which illuminates one of possible mechanisms underlying COVID-19 severity. This study also highlights the importance of dynamically monitoring the plasma levels of VWF/ADAMTS13 after SARS-CoV-2 infection, and facilitates the development of treatment strategy for controlling COVID-19 severity and associated thrombotic complication.

KOH-activated porous biochar with high specific surface area for adsorptive removal of chromium (VI) and naphthalene from water: Affecting factors, mechanisms and reusability exploration

Herein, a high-performance porous biochar described as PBCKOH was successfully synthesized by two-step pyrolysis of corn straw with chemical activation of KOH, and was employed for the elimination of Cr(VI) and naphthalene (NAP) from water. Benefiting from KOH activation, the PBCKOH was found to possess huge specific surface area of 2183.80 m2/g and many well-developed micropores with average particle size of 2.75 nm and main pore diameters distribution from 1 to 2 nm. The PBCKOH presented an excellent adsorption performance with a theoretical monolayer uptake of 116.97 mg/g for Cr(VI) and a heterogeneous adsorption capacity of 450.43 mg/g for NAP. The uptake equilibrium was attained within about 120 min for Cr(VI), while about 180 min for NAP following avrami fractional-order model, revealing the existence of multiple kinetics during the adsorption. The thermodynamic results showed that the uptake of both Cr(VI) and NAP occurred spontaneously (-ΔG°), while in an endothermic nature for Cr(VI) (+ΔH°) and an exothermic characteristic for NAP (-ΔH°) with different randomness. Furthermore, the PBCKOH was believed to enhance the Cr(VI) adsorption mainly through the combination of electrostatic attraction, complexation, ion exchange and reduction action, while achieving the high NAP uptake by pore filling and π-πstacking interactions.

Longitudinal peripheral blood transcriptional analysis of COVID-19 patients captures disease progression and reveals potential biomarkers (preprint)

COVID-19, caused by SARS-CoV-2, is an acute self-resolving disease in most of the patients, but some patients can develop a severe illness or even death. To characterize the host responses and identify potential biomarkers during disease progression, we performed a longitudinal transcriptome analysis for peripheral blood mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset to recovery. We found that PBMCs at different COVID-19 disease stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia may exacerbate disorders in blood coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression and predicting the risk of severity.