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Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03–1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of dynamically monitored levels of plasma prothrombin fragment1+2 (F1+2) and D-dimer in the process of thrombolysis with urokinase. Methods: Blood samples were collected at baseline and at hours 1, 2, 3, 6, 12, 24, 48, 72, and 96 after urokinase infusion finished. The levels of plasma F1+2 and D-dimer of 45 patients who received urokinase intravenous infusion were assayed by ELISA and fluorescent immunoassay, and analysed dynamically with their clinical outcomes. Results: The levels of plasma F1+2 and D-dimer in patients before urokinase thrombolysis were significantly higher than age- and gender-matched normal controls (all p<0.05). After urokinase infusion was finished, three kinds of dynamic changes of plasma F1+2 and D-dimer with different clinical outcomes appeared. In effective subgroup (n=30), the plasma D-dimer increased quickly and reached to the peak at the third hour, remained at the higher level for more than 24 hours, and then decreased gradually; while plasma F1+2 began to decrease at the second hour and promptly approached to its trough near the baseline, after 24 hours. In non-effective subgroup, the D-dimer was slightly higher than its baseline and much lower than that in the effective subgroup, and the most high level appeared at the sixth hour and decreased quickly; moreover, the peak of F1+2 appeared at the third hour and remained at high level for more than 40 hours, and then decreased to the trough which was near the baseline. In cerebral hemorrhage subgroup, the D-dimer peak (2551 ± 68 μg/l) appeared at the third hour, which was 1.5-fold higher than that in effective subgroup (1895 ± 89 μg/l), 5.0-fold higher than that in non-effective subgroup (531 ± 46 μg/l), and 6.0-fold higher than its baseline, and kept higher level for more than 72 hours; meanwhile, the F1+2 decreased remarkably and reached the trough which was far below its baseline. Conclusions: Plasma F1+2 and D-dimer levels are closely related to the different clinical outcomes after urokinase thrombolysis. Thrombotic–fibrinolytic imbalance might be one of the main reasons which affected the prognosis of ischemia stroke. Dynamic assay of the two biomarkers in plasma besides clinical observation might be helpful to predict the early prognosis of acute ischemia stroke during the process of urokinase thrombolysis. [ABSTRACT FROM AUTHOR]

Objective: To explore the value of dynamically monitored levels of plasma prothrombin fragment(1+2) (F(1+2)) and D-dimer in the process of thrombolysis with urokinase., Methods: Blood samples were collected at baseline and at hours 1, 2, 3, 6, 12, 24, 48, 72, and 96 after urokinase infusion finished. The levels of plasma F(1+2) and D-dimer of 45 patients who received urokinase intravenous infusion were assayed by ELISA and fluorescent immunoassay, and analysed dynamically with their clinical outcomes., Results: The levels of plasma F(1+2) and D-dimer in patients before urokinase thrombolysis were significantly higher than age- and gender-matched normal controls (all p<0.05). After urokinase infusion was finished, three kinds of dynamic changes of plasma F(1+2) and D-dimer with different clinical outcomes appeared. In effective subgroup (n=30), the plasma D-dimer increased quickly and reached to the peak at the third hour, remained at the higher level for more than 24 hours, and then decreased gradually; while plasma F(1+2) began to decrease at the second hour and promptly approached to its trough near the baseline, after 24 hours. In non-effective subgroup, the D-dimer was slightly higher than its baseline and much lower than that in the effective subgroup, and the most high level appeared at the sixth hour and decreased quickly; moreover, the peak of F(1+2) appeared at the third hour and remained at high level for more than 40 hours, and then decreased to the trough which was near the baseline. In cerebral hemorrhage subgroup, the D-dimer peak (2551 +/- 68 microg/l) appeared at the third hour, which was 1.5-fold higher than that in effective subgroup (1895 +/- 89 microg/l), 5.0-fold higher than that in non-effective subgroup (531 +/- 46 microg/l), and 6.0-fold higher than its baseline, and kept higher level for more than 72 hours; meanwhile, the F(1+2) decreased remarkably and reached the trough which was far below its baseline., Conclusions: Plasma F(1+2) and D-dimer levels are closely related to the different clinical outcomes after urokinase thrombolysis. Thrombotic-fibrinolytic imbalance might be one of the main reasons which affected the prognosis of ischemia stroke. Dynamic assay of the two biomarkers in plasma besides clinical observation might be helpful to predict the early prognosis of acute ischemia stroke during the process of urokinase thrombolysis.