A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up

Abstract

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021–August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm2 for PDI and 4.9 J/cm2 for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12–24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of “long COVID” symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.

ROS conversion promotes the bactericidal efficiency of Eosin Y based photodynamic therapy

“…As reported, in the case of the administration of antibiotics against bacteria-associated infections, more than 1000 times as much antibiotic is needed to kill bacteria embedded in a biofilm as compared to an equal amount of planktonic bacteria. [25][26][27][28] This EOS/HEPES PDT system, taking advantage of the visible light and "ROS conversion" strategies (Fig. 5c), is a high-efficiency antibacterial approach without the development of multidrug-resistance.…”

Can photobiomodulation restore anosmia and ageusia induced by COVID‐19? A pilot clinical study

“…In this context, PBM can act as an antioxidant-neuromodulator-homeostatic tool in reducing oxidative stress (OS), increasing adenosine triphosphate (ATP) synthesis and enhancing nitric oxide (NO) production of injured peripheral neurons, resulting in upregulating the host immune response. Additionally, NO interaction with reactive oxygen species (ROS) and nitrogen facilitates antimicrobial molecular species production, including SASR-CoV-2 virus by disrupting RNA replication [15][16][17].…”

Photodynamic Action of Curcumin and Methylene Blue against Bacteria and SARS-CoV-2—A Review

“…Methylene blue is an FDA-approved PS [ 44 ]; curcumin is not approved as a PS and is only available in the United States as a dietary supplement [ 45 ]. However, curcumin has been used as a photosensitizer in PDT for a long time, especially in clinical studies.…”