ABSTRACT

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered for them. After identifying the possible markers for the therapeutic window, we then divided the patients, based on whether they were treated with corticosteroids within the therapeutic window, into the early-start group and control group. We identified that the therapeutic window for corticosteroids was characterized by a marked radiographic progression and lactase dehydrogenase (LDH) less than two times the upper limit of normal (ULN). The Shanghai cohort comprised of 68 patients, including 47 in the early-start group and 21 in the control group. The proportion of patients requiring invasive mechanical ventilation was significantly lower in the early-start group than in the control group (10.6% vs. 33.3%, difference, 22.7%, 95% confidence interval 2.6–44.8%). Among the validation cohort of 51 patients, similar difference of the primary outcome was observed (45.0% vs. 74.2%, P = 0.035). Among COVID-19 patients with marked radiologic progression, short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation.

 抽象的

患有 2019 年冠状病毒病 (COVID-19) 的危重患者值得严重关注。这些患者在出现急性呼吸窘迫综合征之前通常会经历过度炎症阶段。在这项研究中，我们检验了这样的假设：短期、低至中等剂量的皮质类固醇在过度炎症的早期阶段（即治疗窗口）使用时将使患者受益。在上海队列和验证队列中，我们招募了显示明显放射学进展的 COVID-19 患者。考虑对他们使用短期、低至中等剂量的皮质类固醇。在确定了治疗窗的可能标志物后，我们根据患者是否在治疗窗内接受皮质类固醇治疗，将其分为早期开始组和对照组。我们发现皮质类固醇的治疗窗的特点是放射学上有显着的进展，并且乳糖酶脱氢酶（LDH）低于正常上限（ULN）的两倍。上海队列由 68 名患者组成，其中早期组 47 名，对照组 21 名。早期开始组需要有创机械通气的患者比例显着低于对照组（10.6% vs. 33.3%，差异22.7%，95%置信区间2.6-44.8%）。在 51 名患者的验证队列中，观察到主要结局的相似差异（45.0% vs. 74.2%， P = 0.035）。在具有明显放射学进展的 COVID-19 患者中，短期、低至中等剂量的皮质类固醇有益于 LDH 水平低于 ULN 两倍的患者，这些患者可能处于过度炎症的早期阶段。