Role of Methylene Blue In Treatment of COVID-19

Methylene blue is an organic chloride salt also known as Methylthioninium chloride. It has several chemical and biological functions. It is a salt that is used as both a dye and a medicine. The intravenous form of methylene blue is approved by the Food and Drug Administration (FDA) for the treatment of methemoglobinemia.¹ 

It possesses antimicrobial, antioxidant, antimalarial, neuroprotective agents, antidepressant, and cardioprotective effects.² Methylene blue, (trade name Rember) is an investigational drug being developed for the treatment of patients with Alzheimer’s disease.³ 

Other clinical applications of methylene blue include improvement of hypotension, an antiseptic in urinary tract infections, treatment of hypoxia, and neurotoxicity.⁴ It is also used as an acid-base indicator, fluorochrome, and histological dye.⁵

Methylene blue in treatment of viral diseases including COVID-19:

The severity of Covid-19 is influenced by pneumonia, myocarditis, ARDS, and inflammation. Here, the body responds fast to pathogens by eliminating its own immune cells. To fight pathogens, bronchial, alveolar, and endothelial cells release a lot of unstable molecules known as free radicals (ROS and RNS). The RNS released can damage our own proteins, lipids, and nucleic acids⁶. The production of these unstable molecules increases during viral infection which activates inflammation-related genes, driving the inflammatory response.

Coronavirus binds to ACE2 receptors to gain entry into lung cells. The study conducted in the United States, suggests that Methylene blue can inhibit the viral attachment and entry of SARS-CoV-2 with ACE2 on the lung cells⁷. When immune cells come into contact with infections, they produce secretory proteins called cytokines, sometimes known as pro-inflammatory cytokines. These cytokines help remove infectious particles from the body, reducing damage. If the immune system's response is abnormal, it might lead to severe disease if it is not addressed⁸. 

The increased generation of cytokines and unstable molecules during COVID-19 causes widespread organ failure. Treatments that target a single cytokine appear to be ineffective because there is a storm of unstable molecules. Despite this, research has shown that Methylene blue is a promising medicine for treating the storm of unstable chemicals. 

Methylene blue blocks the synthesis of unstable molecules (ROS and RNS). It is also seen in inhibiting the production of cytokines by reducing the amplitude of signals which activates inflammatory factors. However, since it is impossible to reverse tissue destruction that has already developed, it is essential to start treatment early. It is advisable to have a daily oral dose at early symptoms of COVID-19⁹.

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Side Effects of Methylene Blue: 

Methylene Blue was till now known mainly as a dye but is now entering the field of cardiac surgery and critical care as a very important therapeutic agent with diverse applications. Methylene blue is a safe drug when used in therapeutic doses (<2 mg/kg). But if high dose of this salt is consumed, tt can cause toxicity in the body. High doses can cause cardiac arrhythmias, decreased cardiac output, and renal blood flow¹⁰. It has been seen to interact with serotonin uptake inhibitor drugs resulting in serotonin toxicity¹¹. It can also interact with drugs such as dapsone to treat skin infections resulting in hemolysis¹². Neonates are more prone to the side effects of methylene blue. It causes respiratory distress, bluish discoloration of skin and urine¹³.

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Conclusion:

Methylene blue is thought to have a protective effect against coronavirus. Although it has positive advantages, it is also linked to negative effects on patients. It is necessary to conduct research on the appropriate dosage of methylene blue that can provide good effects while reducing negative effects. Because methylene blue has been demonstrated to be beneficial in a variety of therapeutic situations, more research is needed to see how the negative effects can be reduced. As a result, Methylene blue can be employed to treat a variety of disorders. 

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References: 

1. https://www.drugs.com/mtm/methylene-blue-injection.html
2. https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6872  
3. https://pubchem.ncbi.nlm.nih.gov/compound/Methylene-blue 
4. https://go.drugbank.com/drugs/DB09241
5. https://en.wikipedia.org/wiki/Methylene_blue 
6. https://pubmed.ncbi.nlm.nih.gov/15230345/ 
7. https://www.frontiersin.org/articles/10.3389/fphar.2020.600372/full#h5 
8. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01446/full#:~:text=COVID%2D19%20infection%20is%20accompanied,in%20an%20excessive%20inflammatory%20reaction 
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728423/#!po=88.4615 
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087269/ 
11. https://pubmed.ncbi.nlm.nih.gov/16978328/ 
12. https://pubmed.ncbi.nlm.nih.gov/12845393/ 
13. https://pubmed.ncbi.nlm.nih.gov/91881/ 

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