Sanei Zahra Sadat, Shahrahmani Fatemeh, Khaleghi Manesh Behrooz, Hamidi-Alamdari Daryoush, Mehrad-Majd Hassan, Mavaji Darban Behzad, Mirdoosti Seyedeh Motahareh, Seddigh-Shamsi Mohsen
Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1915-1924. doi: 10.1007/s00210-024-03371-6. Epub 2024 Aug 29.
Around the world, the COVID-19 pandemic has presented many difficulties, and acute respiratory distress syndrome (ARDS) has become a major worry. The antiviral and anti-inflammatory characteristics of methylene blue (MB) have garnered interest for potential medicinal applications. The object of the current study is to assess the effect of orally administered MB on the treatment of ARDS associated with COVID-19.
A randomized clinical study was carried out on 122 hospitalized patients who had ARDS related to COVID-19. Patients who met the eligibility requirements were randomized at random to either the control group (CG) (n = 60) or the intervention group (IG) (n = 62). Standard treatments were administered to both groups, with the addition of oral MB to the IG. Clinical outcomes, including SpO2 levels, CRP levels were assessed on the third and fifth days. Additionally, at the time of discharge, patients' assessments were made in terms of APACHE II scores, SOFA scores, LDH and CRP levels, SpO2, and respiratory rate in comparison to the day prior to the intervention. Patients were followed for mortality outcomes at one month and three months after the intervention.
Significant changes were observed in SpO2 levels over time (P < 0.001) and between groups (P = 0.022), with higher levels in the MB-treated group. The interaction between time and group (P = 0.019) indicated a stronger increase in SpO2 in the IG, with the IG's SpO2 level increasing by 6.42%. Furthermore, CRP levels showed significant changes over time (P < 0.001), but not between groups (P = 0.092). However, the interaction between group and CRP change over time (P = 0.019) suggested a distinct pattern of CRP decrease in the IG. Significant improvement in RR, SpO2, CRP, and APACHE II score were found according to discharge results. However, in terms of SpO2 and the APACHE II score, this improvement was noteworthy for IG. The length of hospitalization and mortality rates at one- and three-month follow-ups did not differ significantly.
Oral administration of MB demonstrated positive effects on improving SpO2 levels and reducing inflammatory markers in COVID-19-related ARDS patients. Despite no significant impact on survival rates or hospitalization length, the study supports the potential efficacy of MB as an alternative treatment for COVID-19 ARDS.
This study was registered with the Iranian Registry of Clinical Trials ( http://www.irct.ir ) under the registration code IRCT20200409047007N2 on 11/29/2021.
在全球范围内，新冠疫情带来了诸多困难，急性呼吸窘迫综合征（ARDS）已成为一大担忧。亚甲蓝（MB）的抗病毒和抗炎特性引发了人们对其潜在医学应用的兴趣。本研究的目的是评估口服亚甲蓝对治疗与新冠相关的急性呼吸窘迫综合征的效果。
对122例因新冠相关急性呼吸窘迫综合征住院的患者进行了一项随机临床研究。符合入选标准的患者被随机分为对照组（CG）（n = 60）或干预组（IG）（n = 62）。两组均给予标准治疗，干预组在此基础上加用口服亚甲蓝。在第三天和第五天评估临床结局，包括血氧饱和度（SpO2）水平、C反应蛋白（CRP）水平。此外，在出院时，与干预前一天相比，对患者进行急性生理与慢性健康状况评分系统II（APACHE II）评分、序贯器官衰竭评估（SOFA）评分、乳酸脱氢酶（LDH）和CRP水平、SpO2及呼吸频率方面的评估。在干预后1个月和3个月对患者进行死亡率随访。
随着时间推移，SpO2水平有显著变化（P < 0.001），且两组间也有显著差异（P = 0.022），亚甲蓝治疗组的SpO2水平更高。时间与组间的交互作用（P = 0.019）表明干预组SpO2升高更明显，干预组的SpO2水平升高了6.42%。此外，CRP水平随时间有显著变化（P < 0.001），但两组间无显著差异（P = 0.092）。然而，组间与CRP随时间变化的交互作用（P = 0.019）表明干预组CRP下降模式明显。根据出院结果，呼吸频率、SpO2、CRP和APACHE II评分有显著改善。然而，就SpO2和APACHE II评分而言，干预组的改善尤为显著。住院时间以及1个月和3个月随访时的死亡率无显著差异。
口服亚甲蓝对改善新冠相关急性呼吸窘迫综合征患者的SpO2水平和降低炎症标志物有积极作用。尽管对生存率和住院时间无显著影响，但该研究支持亚甲蓝作为新冠急性呼吸窘迫综合征替代治疗的潜在疗效。
本研究于2021年11月29日在伊朗临床试验注册中心（http://www.irct.ir）注册，注册号为IRCT20200409047007N2。
