Neutrophil Elastase Inhibitor (Sivelestat) in the Treatment of Acute Respiratory Distress Syndrome Induced by COVID- 19: A Multicenter Retrospective Cohort Study (preprint)

Background Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19.Methods A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan-Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of < 0.05 was considered statistically significant.Results A total of 387 patients met inclusion criteria, including 259 patients (66.9%) who were treated with sivelestat. In 158 patients matched on the propensity for treatment, receipt of sivelestat was associated with improved oxygenation, decreased Murray lung injury score, increased non-mechanical ventilation time within 28 days, increased alive and ICU-free days within 28 days (HR, 1.85; 95% CI, 1.29 to 2.64; log-rank p < 0.001), shortened ICU stay and ultimately improved survival (HR, 2.78; 95% CI, 1.32 to 5.88; log-rank p = 0.0074).Conclusions Among patients with ARDS induce by COVID-19, sivelestat administration is associated with improved clinical outcomes.

Rationally designed multimeric nanovaccines using icosahedral DNA origami for molecularly controlled display of SARS-CoV-2 receptor binding domain (preprint)

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employed an icosahedral DNA origami (ICO) as a display particle for SARS-CoV-2 RBD nanovaccines. The morphology and diameter of the particles were close to those of the virus. The surface addressability of the DNA origami permitted facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoked stronger and more enduring humoral and T cell immune responses in mouse models compared to soluble RBD antigens. Our vaccines activated similar humoral immunity and slightly stronger cellular immunity compared to mRNA vaccines. These results provide reference principles for the rational design of nanovaccines and exemplify the utility of DNA origami as a display platform for vaccines against infectious disease.

Volunteer Rescue Dispatch during the Coronavirus Disease 2019 Epidemic: Using the Recruitment of Volunteers for Pneumonia Epidemic Prevention and Control in Chun'an County as an Example

To solve the problem of volunteer dispatch during the Coronavirus Disease 2019 (COVID-19) epidemic, a many-to-many two-sided matching volunteer dispatch method based on an improved predator-search algorithm is proposed. First, different evaluation index sets for volunteers and rescue tasks were developed, and weightings were determined using the analytic hierarchy process. Subsequently, the actual and expected values of the different indicators of the two parties were determined, and the triangular fuzzy number was used to calculate the satisfaction of the two parties. Based on this number, we used a linear weighting method to calculate the combined satisfaction and build a many-to-many two-sided matching model according to the demands of both parties. Subsequently, an improved predator-search algorithm was used to solve the model. Finally, taking the recruitment of volunteers for pneumonia epidemic prevention and control in Chun'an County as an example, the method proposed in our study was verified. A comparison and analysis of the results further demonstrated the feasibility and advantages of this method.