Methylene Blue: A Scientific Breakthrough for COVID-19?

Can methylene blue, an inexpensive drug that’s routinely used in hospital emergency rooms, cure COVID-19?  Emerging evidence shows MB can rapidly inactivate the SARS-CoV-2 virus.

Almost immediately following the declaration of the COVID-19 pandemic by the World Health Organization in March 2020, scientists got to work studying ways to inhibit replication of the virus.  One medicine with great promise is methylene blue – a dye originally developed for the fabric industry in the 1800s which turned out to be highly medicinal for many diseases, including viruses.

Methylene blue has long been known for its potent anti-viral properties against deadly viruses.  Zika(15), West Nile(16), Ebola(17), HIV(18), Hepatitis(18), Herpes(21), Dengue(22), and many more, have all been scientifically reported to be rapidly inactivated by methylene blue. Can methylene blue also inactivate the virus responsible for COVID-19? 

In this article, I’m going to present evidence that methylene blue can 1) prevent COVID-19 transmission, 2) inactivate the COVID-19 virus, and  3) heal patients who have already been infected, perhaps better than any other medicine known.

Last but not least, a brand new randomized clinical trial tested oral methylene blue on hospitalized covid patients and showed the treatment “significantly improved SpO₂ (oxygen saturation) and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality.”(R)

1) Can Methylene Blue Prevent COVID-19?

The subpopulation of people with the highest risk of a diagnosis of COVID-19 are the elderly.  Elderly cancer patients have an even greater risk. Any medicine that can prevent infection in elderly terminal cancer patients is a superstar among medicines for COVID-19. This research has been done.

In 2020, scientists conducted an experiment on 2500 elderly terminal cancer patients by giving them methylene blue and seeing how many of them contracted the disease. 

The results?  None of the patients developed COVID-19.(R)

Is this a coincidence? Or is methylene blue a world class preventative medicine against COVID-19 infection?

2) Can Methylene Blue Inactivate SARS-CoV-2?

In March 2020, the same month as the pandemic was declared, a study was published showing methylene blue can “effectively eliminate SARS-CoV-2 within 2 minutes.”(R).  2 minutes!?  Why wasn’t this on the news?

“We propose that methylene blue is a promising drug for treatment of COVID-19,” wrote French scientists in a follow-up study in October 2020, in which very low doses of methylene blue showed powerful anti-viral activity against SARS-CoV-2.(R)

Not only has methylene blue proven itself valuable for treating COVID-19 patients, but it’s already fully stocked in hospitals.  (Methylene blue is the first line of treatment in hospital emergency rooms for poisonings and overdoses.) But instead of methylene blue, the treatment of choice has been mechanical ventilators, which are proven to make the health of patients worse.  If you haven’t already, be sure to read my article on mechanical ventilators.

3) ‘Methylene Blue Derivative Cures COVID’, says Dr Stella Immanuel

You may have heard the 2020 news that Nigerian doctor Stella Immanuel has been successfully using hydroxychloroquine to cure hundreds of COVID patients. 

This news story was quickly censored and pulled from social media websites. Apparently their pharmaceutical investors would rather make billions of dollars selling vaccines then heal people.

Hydroxychloroquine is to this day the primary treatment for Malaria, and those looking to obtain it as a treatment or preventative for COVID-19 know it can be difficult to find.  Here’s some good news if you’re one of these people: hydroxychloroquine is derived from methylene blue.  In other words, methylene blue is the parent compound of hydroxychloroquine; it’s cheap, easily obtainable, and can be used in its place.

How Does Methylene Blue Treat COVID?

Recent research has shown that COVID-19 patients often experience high levels of oxidized forms of hemoglobin, called methemoglobin, just like patients with methemoglobinemia.  “Severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity.”(R)  In fact, it has been said that methemoglobin “may play a central role in the pathogenesis of critical COVID-19 disease.”(R)  How can methylene blue help this situation?

Methylene blue is FDA approved to treat methemoglobinemia, a situation where the oxygen-carrying capacity of red blood cells is impaired.  Methylene blue is extremely effective at turning the oxidized hemoglobin back to its normal state, thus restoring oxygen transport throughout the blood.  As a result, the hypoxia experienced by people with methemoglobinemia (or COVID-19) is resolved and the patient’s health is restored.  Now you know how it works!

The following is another mechanism by which methylene blue could help COVID-19 patients.

Study: Methylene Blue Effective Against Pneumonia

In its most severe state, COVID-19 infection manifests itself as pneumonia, which includes damage to the lungs of patients.  Methylene blue has been studied as a treatment for pneumonia independent of COVID-19 infection and its results are promising.

A 2014 study tested methylene blue on rats with induced pneumonia.(R)  Methylene blue therapy was administered to the rats for 7 days at a dose of 2mg/kg/day. 

When researchers examined the lungs of the rats at the end of the 7 day trial, they found that methylene blue significantly inhibited inflammation, edema, fibrosis, and other biomarkers of lung damage. 

Since COVID-19 patients experience similar lung damage, this study represents indirect evidence that the damage seen in the lungs of severe COVID-19 patients might also benefit from methylene blue.

Methylene Blue COVID-19 Treatment Protocol

Evidence shows overwhelmingly that methylene blue is an effective preventative and treatment for COVID-19.  But why stop there?

You may have read my article Can Red Light Therapy Cure COVID-19?, in which I present evidence that red light therapy can accelerate healing of COVID patients.  What happens when you combine red light therapy with methylene blue?

When you combine light therapy with methylene blue therapy you get a breakthrough therapy called photodynamic therapy (PDT).  PDT has shown to synergistically fight viruses, including COVID-19(R), more powerfully than methylene blue therapy or red light therapy alone.

I don’t give out medical advice, and nothing in this article should be interpreted as such, but if I had COVID-19, here’s the photodynamic therapy protocol I would use to heal myself:

• Methylene Blue: 20 drops in juice in the morning and 20 drops in juice before bed
• Red light therapy: Sit under a red light therapy device for 30 minutes immediately following methylene blue administration.

Be sure to shine the red light directly on your bare skin during treatment, as clothing is a very efficient blocker of red and near-infrared light.  Also, the closer the light is to your body, the more deeply it will penetrate into tissues and the more photons of light will reach your cells, making it more effective.  For best results, position the light between 0-6 inches from the body.

Conclusions

Methylene blue has proven itself as a powerful anti-viral medicine for many popular viruses, including the SARS-CoV-2 virus responsible for COVID-19. 

Even in elderly terminal cancer patients – the population most vulnerable to infection by SARS-CoV-2 – evidence suggests methylene blue can completely prevent infection. 

The work of Dr Stella Immanuel has shown that hydroxychloroquine, a derivative of methylene blue, can powerfully restore health in infected patients.

COVID-19 manifests in many ways similar to the condition methemoglobinemia, which methylene blue has been FDA approved to treat.  This is one of many reasons methylene blue is so valuable for treating COVID-19.

Combine methylene blue with red light therapy and you’ve got yourself an even more potent therapy for treating COVID-19. 

Those who like to take their health into their own hands will be happy to hear that photodynamic therapy is one of the most potent treatment combinations against a multitude of viruses, and many other diseases.

If you want to learn more about methylene blue, checkout my bestselling book on the subject at endalldisease.com/books

References

Inactivation of Zika virus in plasma and derivatives by four different methods

Yancui Wang ¹, Kai Ren ¹, Xinzhong Liao ¹, Guanwen Luo ², Kattareeya Kumthip ³, Nipapan Leetrakool ⁴, Shilin Li ¹, Limin Chen ^1 5, Chunhui Yang ¹, Yongjun Chen ¹Affiliations expand

• PMID: 31389019
• DOI: 10.1002/jmv.25538

Abstract

Zika virus (ZIKV) is an emerging arbovirus with increasing prevalence in recent years. To reduce the risk of ZIKV transmission by transfusion, some mitigation strategies were recommended based on pathogen reduction technologies for blood products. In this study, we aimed to study the efficacy of several common pathogen reduction methods in the inactivation of ZIKV. The fresh frozen plasma and derivatives were spiked with a high titer of ZIKV or Sindbis virus (SINV). Viral titers and ZIKV RNA were measured before and after the inactivation treatment by methylene blue (MB), solvent/detergent (S/D), pasteurization, and low pH. The mean ZIKV infectivity titers in plasma and derivatives were 7.08 ± 0.14, 5.17 ± 0.14, 7.08 ± 0.14, and 5.80 ± 0.14 log₁₀ TCID₅₀ /mL, respectively before MB, S/D, pasteurization, and low pH inactivation. We found no detectable ZIKV RNA after five successive passages of inoculation on host cells, indicating there is no infectivity after inactivation. Similar inactivation results were observed for SINV. In conclusion, we achieved robust ZIKV inactivation through the four inactivation procedures in several blood products. These findings suggest that the pathogen reduction technologies commonly applied in plasma and derivatives have the capacity to mitigate the risk of ZIKV transmission by transfusion.

Methylene blue photoinactivation abolishes West Nile virus infectivity in vivo

James F Papin ¹, Robert A Floyd, Dirk P DittmerAffiliations expand

• PMID: 16118025
• DOI: 10.1016/j.antiviral.2005.07.001

Abstract

The prevalence of West Nile virus (WNV) infections and associated morbidity has accelerated in recent years. Of particular concern is the recent demonstration that this virus can be transmitted by blood products and can cause severe illness and mortality in transfusion recipients. We have evaluated methylene blue (MB)+light as a safe and cost-effective means to inactivate WNV in vitro. This regimen inactivated WNV with an IC50 of 0.10 microM. Up to 10(7)pfu/ml of WNV could be inactivated by MB+light with no residual infectivity. MB+light inactivated three primary WNV isolates from the years 1999, 2002 and 2003 and prevented mortality in a murine model for WNV infection. Since MB is already approved for human use at a dose of 100mg/kg/day, we conjecture that MB+light treatment of blood products for high-risk patients will be efficacious and suitable for use in resource-limited settings.

Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively

Markus Eickmann, ^{1 , †} Ute Gravemann, ^{2 , †} Wiebke Handke, ² Frank Tolksdorf, ³ Stefan Reichenberg, ³ Thomas H. Müller, ² and Axel Seltsam ²Author informationArticle notesCopyright and License informationDisclaimerThis article has been cited by other articles in PMC.Go to:

Abstract

BACKGROUND

Ebola virus (EBOV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) have been identified as potential threats to blood safety. This study investigated the efficacy of the THERAFLEX UV‐Platelets and THERAFLEX MB‐Plasma pathogen inactivation systems to inactivate EBOV and MERS‐CoV in platelet concentrates (PCs) and plasma, respectively.

STUDY DESIGN AND METHODS

PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity.

RESULTS

UVC reduced EBOV (≥4.5 log) and MERS‐CoV (≥3.7 log) infectivity in PCs to the limit of detection, and MB/light decreased EBOV (≥4.6 log) and MERS‐CoV (≥3.3 log) titers in plasma to nondetectable levels.

CONCLUSIONS

Both THERAFLEX UV‐Platelets (UVC) and THERAFLEX MB‐Plasma (MB/light) effectively reduce EBOV and MERS‐CoV infectivity in platelets and plasma, respectively.

Viral Inactivation of Human Osteochondral Grafts with Methylene Blue and Light

Donna M. Squillace,¹Zhixing Zhao,¹Gazell M. Call,¹Jizong Gao,¹ and Jian Q. Yao²Author informationCopyright and License informationDisclaimerThis article has been cited by other articles in PMC.Go to:

Abstract

Objective:

Cartilage injury is one of the most common disorders of synovial joints. Fresh osteochondral allografts are becoming a standard treatment; however, they are supply constrained with a potential risk of disease transmission. There are no known virucidal processes available for osteochondral allografts and most methods presently available are detrimental to cartilage. Methylene blue light treatment has been shown to be successful in the literature for viral inactivation of fresh frozen plasma. The purpose of this study was to determine the capacity of methylene blue light treatment to inactivate a panel of clinically relevant viruses inoculated onto osteochondral allografts.

Design:

Osteochondral grafts recovered from human cadaveric knees were inoculated with one of the following viruses: bovine viral diarrhea virus (BVDV), hepatitis A virus (HAV), human immunodeficiency virus type 1 (HIV-1), porcine parvovirus (PPV), and pseudorabies virus (PrV). The samples were processed through a methylene blue light treatment, which consisted of an initial soak in nonilluminated circulating methylene blue at ambient temperature, followed by light exposure with circulating methylene blue at cool temperatures. The final titer was compared with the recovery control for the viral log reduction.

Results:

HIV-1, BVDV, and PrV were reduced to nondetectable levels while HAV and PPV were reduced by 3.1 and 5.6 logs, respectively.

Conclusions:

The methylene blue light treatment was effective in reducing (a) enveloped DNA and RNA viruses to nondetectable levels and (b) nonenveloped DNA and RNA viruses of inoculated human osteochondral grafts by 3.1 to 5.6 logs. This study demonstrates the first practical method for significantly reducing viral load in osteochondral implants.

Hepatitis C and human immunodeficiency virus RNA degradation by methylene blue/light treatment of human plasma

K Müller-Breitkreutz ¹, H MohrAffiliations expand

• PMID: 9783692
• DOI: 10.1002/(sici)1096-9071(199811)56:3<239::aid-jmv11>3.0.co;2-9

Abstract

Treatment of human plasma with methylene blue in combination with visible light (MB/light) inactivates several bloodborne viruses such as retro viruses and herpes viruses. The viral nucleic acid is thought to be a critical target for the inactivation procedure. We investigated the effects of photodynamic treatment on the RNA of hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) using Amplicor reverse transcriptase polymerase chain reaction (RT-PCR), which detects and quantifies a small fragment of the viral RNA. The detectable HCV RNA load (5-nontranslated region) in infected human plasma declined by 94-97 % within 10 min of illumination in small-scale experiments (1-2 ml vol.). Since the same effect was observed in both anti-HCV positive and negative (“window”) samples, it can be concluded that HCV antibodies do not influence virus inactivation by photodynamic treatment. The effect of treatment on RT-PCR signals of HIV-1, which is known to be inactivated rapidly by MB/light treatment, was examined. Plasma was infected with HIV-1 and subjected to RT-PCR, which detected a part of the gag gene. The extent and kinetics of PCR signal reduction induced by MB/light treatment were similar to those observed for HCV. Experiments at production scale where single plasma units (300 ml) were infected with HCV showed reduction rates of PCR signals consistent with those measured in the small-scale experiments. The data support the view that MB/light treatment affects the viral nucleic acids and suggest that HCV is susceptible to the procedure.

Inactivation of dengue virus by methylene blue/narrow bandwidth light system

Qing Huang, Wei-Ling Fu,^*Bing Chen, Jun-Fu Huang, Xue Zhang, and Qiang XueAuthor informationArticle notesCopyright and License informationDisclaimerThis article has been cited by other articles in PMC.Go to:

Abstract

Peracetic acid was one of the most commonly used disinfectants on solid surfaces in hospitals or public places. However, peracetic acid is an environmental toxin. Therefore, safer, alternative disinfectants or disinfectant systems should be developed. Because photodynamic virus inactivation with methylene blue (MB)/light system has proven effective in blood banking, MB was selected as a photosensitizing agent, dengue virus as a model virus for enveloped RNA viruses, and an in-house fabricated narrow bandwidth light system overlapping the absorption spectrum of MB as the light source. Dengue virus was mixed with different concentrations of MB, and illuminated by the narrow bandwidth light system under different illumination distances and times. The amount of dengue virus remaining was evaluated by plaque forming assays. Results showed that the concentration of MB working solution, illumination intensity of light source, illumination distance and time were four key factors affecting efficiency of virus inactivation using the MB/narrow bandwidth light system. Dengue virus could be completely inactivated at 2.5 m in 5 min when MB ⩾ 1.0 μg/ml. However, when the distance reached 3.0 m, only greater concentrations of MB (2.0 μg/ml) could completely inactivate virus in a reasonably short time (20 min), and smaller concentrations of MB (1.0 μg/ml) could only completely inactivate virus using longer times (25 min). The results of this virus inactivation model indicate that our MB/narrow bandwidth light system provides a powerful, easy way to inactivate dengue viruses.

A COHORT OF CANCER PATIENTS WITH NO REPORTED CASES OF SARS-COV-2 INFECTION : THE POSSIBLE PREVENTIVE ROLE OF METHYLENE BLUE

Marc Henry^1*, Mireille Summa², Louis Patrick³, Laurent Schwartz⁴

1 Université de Strasbourg, Chimie Moléculaire du Solide, Institut Le Bel, Strasbourg.
2 Ceremade, Université Paris Dauphine
3 Association Espoir Métabolique
4 Assistance Publique des Hôpitaux de Paris, Paris, France.

Abstract

We report the case of a cohort of 2500 French patients treated among others with methylene blue for cancer care. During the COVID-19 epidemics none of them developed influenza-like illness. Albeit this lack of infection might be by chance alone, it is possible that methylene blue might have a preventive effect for COVID-19 infection. This is in line with the antiviral activity of Chloroquine, a Methylene blue derivative.

Both Chloroquine and Methylene blue have strong antiviral and anti- inflammatory properties probably linked to the change in intracellular pH and redox state.

Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for the COVID-19 outbreak

Changzhong Jin, Bin Yu, Jie Zhang, Hao Wu, Xipeng Zhou, Hangping Yao, Fumin Liu, Xiangyun Lu, Linfang Cheng, Miao Jiang, Nanping Wu

Background  

With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus (SARS-CoV-2) attracted worldwide attention. Although coronaviruses typically infect the upper or lower respiratory tract, discovery of the virus in plasma is common. Therefore, the risk of transmitting coronavirus through transfusion of blood products remains. As more asymptomatic infections are found in COVID-19 cases, blood safety is shown to be particularly important, especially in endemic areas.

Study Design and Methods

BX-1, an ‘AIDS treatment instrument’ based on methylene blue (MB) photochemical technology, developed by Boxin (Beijing) Biotechnology Development LTD, has proven that inactivation of lipid-enveloped viruses such as HIV-1 in plasma has high efficiency, without damage to other components in the plasma, and proved safe and reliable in clinical trials of HIV treatment. In order to confirm the inactivation effect of BX-1 in SARS-CoV-2, we used the SARS-CoV-2 virus strain isolated from Zhejiang University for plasma virus inactivation studies.

Results and Conclusion

BX-1 can effectively eliminate SARS-CoV-2 within 2 mins, and the virus titer decline can reach 4.5 log10 TCID50/mL. Faced with the expanding epidemic, BX-1 is safe for blood transfusion and plasma transfusion therapy in recovery patients, and the inactivated vaccine preparation has great potential for treatment in the current outbreak.

Methylene blue inhibits replication of SARS-CoV-2 in vitro

Mathieu Gendrot ¹, Julien Andreani ², Isabelle Duflot ², Manon Boxberger ², Marion Le Bideau ², Joel Mosnier ³, Priscilla Jardot ², Isabelle Fonta ³, Clara Rolland ², Hervé Bogreau ³, Sébastien Hutter ², Bernard La Scola ⁴, Bruno Pradines ⁵Affiliations expand

• PMID: 33075512
• PMCID: PMC7566888
• DOI: 10.1016/j.ijantimicag.2020.106202

Free PMC article

Abstract

In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. Currently there is no antiviral treatment recommended against SARS-CoV-2. Identifying effective antiviral drugs is urgently required. Methylene blue has already demonstrated in vitro antiviral activity in photodynamic therapy as well as antibacterial, antifungal and antiparasitic activities in non-photodynamic assays. In this study. non-photoactivated methylene blue showed in vitro activity at very low micromolar range with an EC₅₀ (median effective concentration) of 0.30 ± 0.03 μM and an EC₉₀ (90% effective concentration) of 0.75 ± 0.21 μM at a multiplicity of infection (MOI) of 0.25 against SARS-CoV-2 (strain IHUMI-3). The EC₅₀ and EC₉₀ values for methylene blue are lower than those obtained for hydroxychloroquine (1.5 μM and 3.0 μM) and azithromycin (20.1 μM and 41.9 μM). The ratios C_max/EC₅₀ and C_max/EC₉₀ in blood for methylene blue were estimated at 10.1 and 4.0, respectively, following oral administration and 33.3 and 13.3 following intravenous administration. Methylene blue EC₅₀ and EC₉₀ values are consistent with concentrations observed in human blood. We propose that methylene blue is a promising drug for treatment of COVID-19. In vivo evaluation in animal experimental models is now required to confirm its antiviral effects on SARS-CoV-2. The potential interest of methylene blue to treat COVID-19 needs to be confirmed by prospective comparative clinical studies.

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

by Felix Scholkmann ^1,2,*,Tanja Restin ²,Marco Ferrari ³ andValentina Quaresima ³¹Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland²Newborn Research Zurich, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland³Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy^*Author to whom correspondence should be addressed.J. Clin. Med.2021, 10(1), 50; https://doi.org/10.3390/jcm10010050

Abstract

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient’s glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.

Application of methylene blue -vitamin C –N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial☆

Author links open overlay panelDaryoush HamidiAlamdari^aAhmad BagheriMoghaddam^bShahramAmini^cMohammad RezaKeramati^dAzam MoradiZarmehri^eAida HamidiAlamdari^fMohammadaminDamsaz^fHamedBanpour^dAmirYarahmadi^gGeorgeKoliakos^h

Abstract

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients’ lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C–N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases.

The effect of methylene blue treatment on aspiration pneumonia

Mehmet Kanter ¹, Sevtap Hekimoglu Sahin ², Umit Nusret Basaran ³, Suleyman Ayvaz ³, Burhan Aksu ³, Mustafa Erboga ⁴, Alkin Colak ²Affiliations expand

• PMID: 25260956
• DOI: 10.1016/j.jss.2014.08.039

Abstract

Background: The study aimed to examine whether methylene blue (MB) prevents different pulmonary aspiration materials-induced lung injury in rats.

Methods: The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250-300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + MB treated, BIO + MB treated, and HCl + MB treated. Saline, BIO, and HCl were injected into the lungs in a volume of 2 mL/kg. After surgical procedure, MB was administered intraperitoneally for 7 days at a daily dose of 2 mg/kg per day. Seven days later, rats were killed, and both lungs in all groups were examined biochemically and histopathologically.

Results: Our findings show that MB inhibits the inflammatory response reducing significantly (P < 0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonary aspiration significantly increased the tissue hydroxyproline content, malondialdehyde levels, and decreased (P < 0.05) the antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities. MB treatment significantly (P < 0.05) decreased the elevated tissue hydroxyproline content and malondialdehyde levels and prevented the inhibition of superoxide dismutase and glutathione peroxidase (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase dUTP nick end labeling, and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with MB therapy.

Conclusions: MB treatment might be beneficial in lung injury and therefore shows potential for clinical use.