Plan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Programa de Residencia en Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Mol Med. 2022 Nov 8;28(1):131. doi: 10.1186/s10020-022-00553-x.
Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.
We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.
We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).
Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
严重 2019 冠状病毒病（COVID-19）所致呼吸衰竭与严重炎症反应有关。乙酰胆碱（ACh）可减轻实验性细菌和病毒感染中的全身炎症反应。吡啶斯的明可延长内源性 ACh 的半衰期，从而可能减轻全身炎症反应。我们旨在确定吡啶斯的明是否可降低重症 COVID-19 成年患者接受有创机械通气（IMV）和死亡的复合结局。
我们进行了一项双盲、安慰剂对照、2/3 期随机对照试验，纳入因确诊的重症 COVID-19 入院但在入组时不需要 IMV 的成年患者，给予口服吡啶斯的明（60 mg/天）或安慰剂作为附加治疗。主要结局为 28 天内接受有创机械通气或死亡的复合结局。次要结局包括炎症标志物和循环细胞因子的减少以及 90 天死亡率。记录并描述与研究治疗相关的不良事件（AE）。
我们共招募了 188 名参与者（每组 94 名）；112 名（59.6%）为男性；中位（IQR）年龄为 52（44-64）岁。由于治疗组主要结局显著减少且招募难度增加，研究提前终止。安慰剂组 22 名（23.4%）参与者和吡啶斯的明组 11 名（11.7%）参与者发生主要结局（风险比，0.47；95%CI，0.24-0.9；P=0.03）。这一效果是由死亡率降低（分别为 19 例和 8 例死亡）驱动的。
我们的数据表明，在标准治疗的基础上加用吡啶斯的明可降低因重症 COVID-19 住院患者的死亡率。
