DataSheet_2_Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir.pdf

A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decreasing progression to respiratory failure and mechanical ventilation. However, some studies have highlighted its lack of efficacy in patients on high-flow oxygen and mechanical ventilation. This study uncovers some underlying immune response differences between responders and non-responders to remdesivir treatment. Immunological analyses revealed an upregulation of tissue repair factors BDNF, PDGF-BB and PIGF-1, as well as an increase in ratio of Th2-associated cytokine IL-4 to Th1-associated cytokine IFN-γ. Serological profiling of IgG subclasses corroborated this observation, with significantly higher magnitude of increase in Th2-associated IgG2 and IgG4 responses. These findings help to identify the mechanisms of immune regulation accompanying successful remdesivir treatment in severe COVID-19 patients.

相当比例的新型冠状病毒肺炎（COVID-19）患者会进展为重症，需接受有创机械通气。这一临床现状凸显了研发可减轻COVID-19病情严重程度的治疗手段的迫切需求。临床试验已证实，瑞德西韦（remdesivir）能够缩短患者的康复时间，降低其进展为呼吸衰竭并需机械通气的风险。但部分研究表明，对于接受高流量氧疗与有创机械通气的患者，瑞德西韦并未展现出明确疗效。本研究揭示了瑞德西韦治疗应答者与无应答者之间潜在的免疫应答差异。免疫学分析显示，组织修复因子脑源性神经营养因子（BDNF）、血小板衍生生长因子BB（PDGF-BB）与胎盘生长因子1（PIGF-1）的表达均出现上调，同时辅助性T细胞2型（Th2）相关细胞因子白细胞介素4（IL-4）与辅助性T细胞1型（Th1）相关细胞因子干扰素γ（IFN-γ）的比值升高。免疫球蛋白G（IgG）亚类的血清学谱型分析验证了上述发现：Th2相关的IgG2与IgG4应答的升高幅度显著更高。上述结果有助于阐明重症COVID-19患者接受瑞德西韦治疗并获得成功应答时所伴随的免疫调控机制。