Abiotic Synthetic Antibody Inhibitor with Broad-Spectrum Neutralization and Antiviral Efficacy against Escaping SARS-CoV-2 Variants.

The rapid emergence and spread of vaccine/antibody-escaping variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious challenges to our efforts in combating corona virus disease 2019 (COVID-19) pandemic. A potent and broad-spectrum neutralizing reagent against these escaping mutants is extremely important for the development of strategies for the prevention and treatment of SARS-CoV-2 infection. We herein report an abiotic synthetic antibody inhibitor as a potential anti-SARS-CoV-2 therapeutic agent. The inhibitor, Aphe-NP14, was selected from a synthetic hydrogel polymer nanoparticle library created by incorporating monomers with functionalities complementary to key residues of the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) involved in human angiotensin-converting enzyme 2 (ACE2) binding. It has high capacity, fast adsorption kinetics, strong affinity, and broad specificity in biologically relevant conditions to both the wild type and the current variants of concern, including Beta, Delta, and Omicron spike RBD. The Aphe-NP14 uptake of spike RBD results in strong blockage of spike RBD-ACE2 interaction and thus potent neutralization efficacy against these escaping spike protein variant pseudotyped viruses. It also inhibits live SARS-CoV-2 virus recognition, entry, replication, and infection in vitro and in vivo. The Aphe-NP14 intranasal administration is found to be safe due to its low in vitro and in vivo toxicity. These results establish a potential application of abiotic synthetic antibody inhibitors in the prevention and treatment of the infection of emerging or possibly future SARS-CoV-2 variants.

Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVES: Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug. METHODS: Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). PRIMARY ENDPOINT: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout. RESULTS: The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported. CONCLUSION: In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications. TRIAL REGISTRATION NUMBER: NCT03486457.

What medical waste management system may cope With COVID-19 pandemic: Lessons from Wuhan.

The global pandemic caused by the 2019 coronavirus (COVID-19) has led to a dramatic increase in medical waste worldwide. This tremendous increase in medical waste is an important transmission medium for the virus and thus poses new and serious challenges to urban medical waste management. This study investigates the response of medical waste management to the COVID-19 pandemic and subsequent changes in Wuhan City based on the most detailed data available, including waste generation, storage, transportation, and disposal. The results show that despite a 5-fold increase in the demand for daily medical waste disposal in the peak period, the quick responses in the storage, transportation, and disposal sectors during the pandemic ensured that all medical waste was disposed of within 24 hours of generation. Furthermore, this paper discusses medical waste management during future emergencies in Wuhan. The ability of the medical waste management system in Wuhan to successfully cope with the rapid increase in medical waste caused by major public health emergencies has important implications for other cities suffering from the pandemic and demonstrates the need to establish resilient medical emergency systems in urban areas.