Introduction
death, COVID-19.CD147
COVID-19 PNEUMONIA, VIRUS, ADVERSE EVENT
The COVID-19 pandemic has swept across the world since 2019, infecting >630 million people and reporting a death toll of over six million. Severe and critical COVID-19 is life-threatening, especially for elder or unvaccinated individuals.Currently, neutralizing antibodies (casirivimab/imdevimab and amubarvimab/romlusevimab) and small molecular compounds (paxlovid and molnupiravir) have obtained approval for treating mild to moderate COVID-19.CD147, a type I transmembrane receptor, has been reported as a novel receptor for SARS-CoV-2 and its variants of concern (VOCs), including alpha, beta, gamma, delta,In phase 1 clinical study (NCT04369586), meplazumab (0.06 mg/kg to 0.56 mg/kg) showed favourable safety results, with no serious adverse event or adverse event grade ≥3 observed in healthy volunteers. The biodistribution study revealed that having reached the lung tissue and remained for >14 days, meplazumab effectively facilitated the treatment of COVID-19 pneumonia.The therapeutic effect of meplazumab was preliminary investigated in an exploratory phase 2 study (NCT04275245) in 17 COVID-19 patients (six severe cases and seven critical cases). The results indicated that meplazumab could improve the discharged and case severity, and reduce the time to virus negative with favourable safety profile, suggesting that meplazumab has the potential of treating severe COVID-19 and this potential needs to be validated in phase 2/3 study with large sample size.Here, we report the results of DEFLECT, an ongoing international multi-centre, seamless, randomized, third-party double-blind, placebo-controlled phase 2/3 trial in hospitalized patients with severe COVID-19, to examine the efficacy and safety of meplazumab. The findings indicated that meplazumab has displayed beneficial results in patients with severe COVID-19, including decreased mortality, improved live discharge without oxygen supplement, and reduced level of viral load and cytokine, along with the established safety and tolerability.