SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation–perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA. Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO2/FiO2 ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis. Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41–68] years. No significant differences in mean PaO2/FiO2 ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7–12 days vs. 12 IQR 9–21 days, p = 0.04). No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results. Trial Registration: Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .

中文翻译：

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西地那非用于治疗 COVID-19 和灌注不匹配患者：一项初步随机试验

SARS-CoV-2 似乎影响肺灌注的调节。通气良好的肺实质区域的低灌注导致通气 - 灌注不匹配，可以使用减影计算机断层扫描血管造影 (sCTA) 来表征。本研究旨在评估口服西地那非治疗 sCTA 灌注异常的 COVID-19 住院患者的疗效。2020 年 8 月至 2021 年 3 月期间，在智利一家能够在需要时提供现场 sCTA 扫描和通气支持的三级护理医院进行了三盲、随机、安慰剂对照试验。总共有 82 名符合条件的成年人入院入院后 24 小时内经 RT-PCR 确认或极可能感染 SARS-COV-2 和 sCTA 的 ED 显示通气良好的肺实质区域灌注异常；42 人被排除在外，40 名参与者在住院后被随机分配（1:1 的比例）。积极干预组接受西地那非（25mg，每天3次，连续7天），对照组以相同方式接受相同的安慰剂胶囊。主要结果是随访期间每天测量的氧合参数的差异（PaO2/FiO2 比率和 Aa 梯度）。次要结局包括入住 ICU、无创通气需求、有创机械通气 (IMV) 和死亡率。分析是在意向治疗的基础上进行的。总共招募了 40 名参与者（安慰剂组 20 名，西地那非组 20 名）；33 [82.5%] 是男性；中位年龄为 57 [IQR 41-68] 岁。组间平均 PaO2/FiO2 比率和 Aa 梯度没有显着差异（重复测量方差分析 p = 0.67 和 p = 0.69）。4 名接受安慰剂的患者需要 IMV，而西地那非组则没有（logrank p = 0.04）。西地那非组患者的中位住院时间明显短于安慰剂组（9 IQR 7-12 天 vs. 12 IQR 9-21 天，p = 0.04）。在氧合参数中没有发现统计学上的显着差异。西地那非治疗对于在 sCTA 中具有特定灌注模式的 COVID-19 患者对 IMV 的需求可能具有潜在的治疗作用。需要进行大规模研究来证实这些结果。试验注册：西地那非治疗 COVID-19 和灌注不匹配患者：一项试验性随机试验，NCT04489446，2020 年 7 月 28 日注册，