<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0034-8376</journal-id>
<journal-title><![CDATA[Revista de investigación clínica]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. invest. clín.]]></abbrev-journal-title>
<issn>0034-8376</issn>
<publisher>
<publisher-name><![CDATA[Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0034-83762021000300190</article-id>
<article-id pub-id-type="doi">10.24875/ric.21000028</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Methylene Blue for Treatment of Hospitalized COVID-19 Patients: A Randomized, Controlled, Open-Label Clinical Trial, Phase 2]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hamidi-Alamdari]]></surname>
<given-names><![CDATA[Daryoush]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hafizi-Lotfabadi]]></surname>
<given-names><![CDATA[Saied]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Bagheri-Moghaddam]]></surname>
<given-names><![CDATA[Ahmad]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Safari]]></surname>
<given-names><![CDATA[Hossin]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Mozdourian]]></surname>
<given-names><![CDATA[Mahnaz]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Javidarabshahi]]></surname>
<given-names><![CDATA[Zahra]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Peivandi-Yazdi]]></surname>
<given-names><![CDATA[Arash]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ali-Zeraati]]></surname>
<given-names><![CDATA[Abass]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sedaghat]]></surname>
<given-names><![CDATA[Alireza]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Poursadegh]]></surname>
<given-names><![CDATA[Farid]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Barazandeh-Ahmadabadi]]></surname>
<given-names><![CDATA[Fatemeh]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Agheli-Rad]]></surname>
<given-names><![CDATA[Marzieh]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Tavousi]]></surname>
<given-names><![CDATA[Seyed M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vojouhi]]></surname>
<given-names><![CDATA[Shohreh]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Amini]]></surname>
<given-names><![CDATA[Shahram]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Amini]]></surname>
<given-names><![CDATA[Mahnaz]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Majid-Hosseini]]></surname>
<given-names><![CDATA[Seyed]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Tavanaee-Sani]]></surname>
<given-names><![CDATA[Ashraf]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ghiabi]]></surname>
<given-names><![CDATA[Amin]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Nabavi-Mahalli]]></surname>
<given-names><![CDATA[Shima]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Morovatdar]]></surname>
<given-names><![CDATA[Negar]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Rajabi]]></surname>
<given-names><![CDATA[Omid]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Koliakos]]></surname>
<given-names><![CDATA[George]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Surgical Oncology Research Center  ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Shariati Hospital Department of Internal Medicine ]]></institution>
<addr-line><![CDATA[Tehran ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Faculty of Medicine Department of Anesthesiology ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Hasheminejad Hospital Infectious Diseases Ward ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Lung Diseases Research Center  ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af6">
<institution><![CDATA[,Faculty of Medicine Kidney Transplantation Complications Research Center ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af7">
<institution><![CDATA[,School of Medicine Metabolic Syndrome Research Center ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af8">
<institution><![CDATA[,Faculty of Medicine Anaesthesiology and Critical Care Lung Research Center ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="Af9">
<institution><![CDATA[,Emamreza Hospital Department of Internal Medicine ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="A10">
<institution><![CDATA[,Emamreza Hospital Department of Infectious diseases ]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="A11">
<institution><![CDATA[,Ghaem Hospital Department of Internal Medicine ]]></institution>
<addr-line><![CDATA[Karaj ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="A12">
<institution><![CDATA[,Faculty of Medicine Imam Reza Hospital Clinical Research Development Unit]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="A13">
<institution><![CDATA[,Mashhad University of Medical Sciences School of Pharmacy Department of Pharmaceutical Control]]></institution>
<addr-line><![CDATA[Mashhad ]]></addr-line>
<country>Iran</country>
</aff>
<aff id="A14">
<institution><![CDATA[,Aristotle University of Thessaloniki Medical School Department of Biochemistry]]></institution>
<addr-line><![CDATA[Thessaloniki ]]></addr-line>
<country>Greece</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>06</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>06</month>
<year>2021</year>
</pub-date>
<volume>73</volume>
<numero>3</numero>
<fpage>190</fpage>
<lpage>198</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S0034-83762021000300190&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S0034-83762021000300190&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S0034-83762021000300190&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT  Background: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients.  Objective: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR).  Methods: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days.  Results: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p &lt; 0.0001) and also the 5th day (for both, p &lt; 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively.  Conclusions: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[COVID-19]]></kwd>
<kwd lng="en"><![CDATA[Treatment]]></kwd>
<kwd lng="en"><![CDATA[Methylene Blue]]></kwd>
<kwd lng="en"><![CDATA[Hypoxemia]]></kwd>
<kwd lng="en"><![CDATA[Mortality]]></kwd>
</kwd-group>
</article-meta>
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