Effectiveness of inactive COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China (preprint)

The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of vaccines against this variant is not fully understood. Using data from a recent large-scale outbreak of COVID-19 in China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with Delta variants. We recruited 476 confirmed cases over the age of 18, of which 42 were severe. After adjusting for age, gender, and comorbidities, patients who received two doses of inactivated vaccine (fully vaccinated) had an 88% reduced risk in progressing to the severe stage (adjusted OR: 0.12, 95% CI: 0.02- 0.45). However, this protective effect was not observed in patients who only received only one dose of the vaccine(adjusted OR: 1.11, 95% CI: 0.51- 2.36). The full immunization offered 100% protection from a severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (OR: 0.26, 95% CI: 0.03-1.23). This is the largest real-world study confirming the effectiveness of inactive COVID-19 vaccines against severe illness in Delta variant-infected patients in Jiangsu, China.

Simeprevir suppresses SARS-CoV-2 replication and synergizes with remdesivir (preprint)

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients. One Sentence SummaryDiscovery of simeprevir as a potent suppressor of SARS-CoV-2 viral replication that synergizes with remdesivir.