Discussion
infection, TNF-α, viral infection
PULMONARY FIBROSIS, DISEASE, VIRAL INFECTION, CYTOKINE STORM, INFECTION
Since the pandemic outbreak, several COVID-19 drugs, including neutralizing monoclonal antibodies, have been approved for commercialization.In DEFLECT, we assessed the therapeutic effect and safety of meplazumab in treating severe COVID-19. This clinical trial was designed to enrol hospitalized patients with severe COVID-19. The therapeutic efficacy was evaluated based on clinical outcomes, including mortality, live discharge, response rate, sustained clinical improvement, viral load, and cytokine/chemokine levels. Our data has showed that meplazumab reduced mortality (CD147, as a universal receptor of the spike protein, is identified to be able to mediate the cellular entry of SARS-CoV-2 and its VOCs, and meplazumab could effectively block the infection and replication, and alleviate the progression of pulmonary fibrosis.Cytokine storms have been reported as a key aspect of COVID-19, and infected patients showed high levels of several key proinflammatory cytokines such as IL-1RA, IL-4, IL-8, IFN-ɣ, MCP-1, MIP-1α, and TNF-α, and higher levels of IL-2 and IL-6 was observed in severe infection.In DEFLECT, meplazumab is clinically effective at all three doses, and there are differences between treated groups and the placebo group in terms of mortality and proportion of subjects alive and discharge without supplemental oxygen on D29. The 0.12 mg/kg dose could decrease mortality, and enhance live discharge without oxygen supplementary significantly (The limitation of this study was that the bias in some demographic variable including the gender and age (elder vs younger). It has reported that males and older age was associated with the disease severity and this demographic bias may influence the therapeutic effect of meplazumab.SARS-CoV-2 is continuously mutating over the past 3 years of the COVID-19 epidemic. Currently, the omicron variants is dominating the world. There is an urgent need to develop new therapeutic strategies for emerging VOCs to control the epidemic. In DEFLECT, for the first time, we develop a first-in-class, receptor blocking, humanized antibody with dual action in alleviating viral infection and cytokine storms with a good safety profile for treatment of COVID-19.