Efficacy and safety of the hyaluronic acid inhibitor Hymecromone for the treatment of COVID-19: study protocol for a single-centre, randomized, controlled, Double-blind Clinical trial (preprint)

IntroductionHyaluronic acid (HA) is one of the main components of glycosaminoglycan (GAG) in proteoglycans. Among patients with novel coronavirus pneumonia, the serum HA content of severe patients was significantly higher than that of mild patients. Therefore, hyaluronic acid inhibitors have the potential to be the treatment of novel coronavirus pneumonia. This study plans to carry out a study on the optimization of the hyaluronic acid inhibitor Hymecromone in the treatment of COVID-19 to improve the therapeutic effect.Methods and analysisThis is a single-center, randomized, parallel controlled, double-blind clinical trial designed to evaluate the efficacy and safety of hymecromone tablets in subjects who confirmed to be infected by the SARS-CoV-2 virus and diagnosed as mild or moderate novel coronavirus pneumonia in China. The subjects in the experimental arm shall receive necessary routine treatment and hymecromone tablets while the control arm shall receive placebo. The study aims to compare the proportion of subjects in the experimental group and the control group who developed disease progression within 28 days after initial treatment. Meanwhile, all subjects will be monitored for safety constantly during the whole study phases.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Zhongshan Hospital Fudan University (identifiers: Clinical Ethical Approval No. B2022-251R).Trial registrationClinicalTrails.org, NCT05386420. Registered 24 May 2022, https://clinicaltrials.gov/ct2/show/NCT05386420Strengths and limitations of this studyThis is one of the first prospective randomized controlled double-blind studies of the efficacy and safety of the hyaluronic acid inhibitor Hymecromone for the treatment of COVID-19. This study will be an innovative clinical intervention strategy, and is expected to provide an effective new treatment plan for the clinical treatment of severe infection with COVID-19. The limitation is it is a single center study, it might need more centers cases to be further external validated.INTRODUCTION

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Nowcast Deep Learning Models For Constraining Zero-Day Pathogen Attacks – Application on Chest Radiographs to Covid-19 (preprint)

Outbreaks due to emergent pathogens like Covid-19 are difficult to contain as the time to gather sufficient information to develop a detection system is outpaced by the speed of transmission. Here we develop a general pneumonia (PNA) CXR Deep Learning (DL) model (MAIL1.0) follow by a second-generation DL model (MAIL2.0) for detection of Covid-19 on chest radiographs (CXR). We validate the models on two prospective cohorts of high-risks patients screened for Covid-19 reverse transcriptase-polymerase chain reaction (RT-PCR). MAIL1.0 has an Area Under the Receiver Operating Characteristics (AUC) of 0.93, sensitivity and specificity of 90.5% and 76.7% in detection of visible pneumonia and MAIL2.0 has an AUC of 0.81, sensitivity and specificity of 84.7% and 71.6%, significantly outperforming radiologists, especially amongst asymptomatic and patients presenting with early symptoms. Nowcast DL models may be an effective tool in helping to constrain the outbreak, particularly in resource-stretched healthcare systems.