Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). Methods This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). Results A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. Conclusion While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

中文翻译：

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评估 RNase 对与 SARS-CoV-2 感染急性后遗症 (PASC) 相关的严重疲劳患者的影响：RSLV-132 的随机 2 期试验

背景 严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) RNA 和 RNA 碎片在感染后在病毒库中持续存在数周至数月，可能引发干扰素产生和慢性炎症。 RSLV-132 是一种生物药物，由具有催化活性的人 RNase1 与人 IgG1 Fc 融合组成，旨在保持在循环中并消化细胞外 RNA。我们假设，从潜伏病毒库中去除 SARS-CoV-2 病毒 RNA 可能会改善与 SARS-CoV-2 感染后急性后遗症 (PASC) 相关的炎症、神经炎症和疲劳。方法 这是一项 2 期、双盲、安慰剂对照随机临床试验，参与者有 24 周 PASC 病史和严重疲劳。该试验的主要终点评估了 6 次静脉注射 RSLV-132 对患者报告结果测量信息系统疲劳简表 7a (PROMIS 疲劳 SF 7a) 中第 71 天相对于基线的平均变化的影响。结果 第 71 天在主要或次要终点方面未观察到统计学上的显着差异。这可能是由于试验期间安慰剂反应增加所致。在试验早期，观察到通过 PROMIS 疲劳 SF 7a、慢性病治疗疲劳功能评估 (FACIT-Fatigue) 和医师整体评估 (PGA) 仪器测量的疲劳状况在统计上显着改善，女性对 RSLV 表现出更大的反应-132 比男性。结论 虽然在第 71 天时疲劳没有统计上显着改善，但较早的时间点显示疲劳和医生整体评估有统计上显着的改善。数据表明，通过增加血清 RNase 活性消除潜伏病毒 RNA 可能会改善 PASC 患者的疲劳。女性对这种方法的反应可能比男性更好。未来的研究将旨在证实这些发现。