Reduction of extracellular vimentin in blood provides protection against SARS-CoV-2 infection

In vitro studies have repeatedly showed that extracellular vimentin (eVIM) promotes the penetration of viruses by acting as an adhesion factor, suggesting that reducing eVIM density in the blood could be an effective approach to treat viral infections. However, despite solid evidence, it has not been previously investigated whether eVIM plays a pathogenic role during viral infections in vivo experiments. Here, we provide in vivo evidence that eVIM plays a critical role during viral infections. The severity of COVID-19 in Roborovski SH101 hamsters was positively correlated with blood concentrations of eVIM during the infection period. The reduction of blood eVIM in the SARS-CoV-2-infected Roborovski SH101 hamster through intravenous injection of hzVSF-v13, a humanized anti-eVIM monoclonal antibody, dramatically improved disease manifestations, such as body weight reduction, body temperature, death rate, and more. It also inhibited the formation of blood clots and systemic inflammation compared to remdesivir or a SARS-CoV-2 neutralizing antibody (6D11F2). Histological examination confirmed the significantly better therapeutic efficacy of anti-eVIM compared to remdesivir or the neutralizing antibody. Quantification of SARS-CoV-2 in the hamsters' lungs revealed that the viral titer in the anti-eVIM-treated groups was 77% to 80% lower than that in the infection group, while remdesivir and the neutralizing antibody resulted in reductions of 41.9% and 34.7% to 44.1%, respectively. We believe that this work provides a foundation for the development of hzVSF-v13 as an antiviral drug for COVID-19.