Transcatheter Endoluminal Phototherapy as a Possible Adjunct Treatment for Patients with COVID-19

Photobiomodulation, Photomedicine, and Laser SurgeryVol. 38, No. 10 Letter to the EditorFree AccessTranscatheter Endoluminal Phototherapy as a Possible Adjunct Treatment for Patients with COVID-19Nicholas N. Kipshidze, Nodar Kipshidze, and Joseph B. HornNicholas N. KipshidzeAddress correspondence to: Nicholas Kipshidze, MD, PhD, DSc, New York Cardiovascular Research, LLC, New York, NY 10019, USA E-mail Address: [email protected]New York Cardiovascular Research, New York, New York, USA.Search for more papers by this author, Nodar KipshidzeNYU Langone Health, New York, New York, USA.Search for more papers by this author, and Joseph B. HornColorado Medical Equipment, Inc., Louisville, Colorado, USA.Search for more papers by this authorPublished Online:7 Oct 2020https://doi.org/10.1089/photob.2020.4884AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail To the Editor:Current treatment options for COVID-19 are largely limited to supportive care and experimental therapies. Published reports of the clinical course of hospitalized patients suffering from COVID-19 noted empiric use of various pharmaceuticals and convalescent plasma.1,2 COVID-19 appears to manifest primarily within the upper and lower respiratory tract, although newer reports also implicate other organ systems (e.g., cardiovascular, digestive, renal, and neurological).2 In light of known anti-infective and anti-inflammatory characteristics of energy of certain visible wavelengths, a localized light-based therapeutic approach could prove to be as effective as, or able to supplement, systemic pharmaceutical administration for this or other similar viral diseases.Far-ultraviolet (UV) light between 180 and 280 nm in wavelength has been shown to inactivate enveloped viruses such as SARS-CoV-2.3 However, the effects of far-UV light on eukaryotic DNA (such as inhibition of DNA replication) has slowed the clinical development of such therapy.However, blue light between 380 and 450 nm also demonstrates a significant antimicrobial effect3–5 that could attenuate or eliminate secondary opportunistic pulmonary bacterial infections in patients with COVID-19. In addition, ultrashort pulsed blue light inactivates viruses through an impulsive stimulated Raman scattering process, resulting in aggregation of viral capsid proteins.3 The mechanism of deactivation of blue light, when delivered in a continuous mode, is not fully defined but may excite endogenous intracellular porphyrins, which then behave as native photosynthesizers. The absorption of photons sequentially leads to energy transfer and the production of highly cytotoxic reactive oxygen species—most notably singlet oxygen (1O2)—in a manner similar to photodynamic therapy.4Of additional note, intraluminal red light illumination (632 nm at 10 mW for 180 sec) restores endothelium and significantly reduces inflammation within injured coronary arteries.6 This wavelength of light (irradiance of 0.95 J/cm2) induces nitric oxide (NO) release,7 which inhibits synthesis of viral RNA and protein and, hence, the SARS-CoV replication cycle.8 This is important, given that virus-induced severe acute respiratory syndromes evince prothrombotic states through modulation of various coagulation-related proteins.9 Coagulopathies in patients with COVID-19 may manifest as pulmonary emboli or as other venous, arterial, or microvascular thromboses associated with severe virus-induced injury of lung endothelium.9 Local pulmonary vasodilation induced by NO may be immediately beneficial to such patients by counteracting pulmonary vascular constriction, which may be further compounded by microthromboses and ensuing states of even lower blood flow. Given the antiviral, antibacterial, anti-inflammatory, and vasculoprotective properties of the blue and red wavelengths of light, we propose to treat patients with COVID-19 by directed energy delivery through an endoluminal microcatheter with an illuminating balloon containing a diffusing fiber-optic array at its distal tip (Fig. 1).FIG. 1. Phototherapy balloon microcatheter. Note discrete lumina for balloon insufflation and for energy delivery by optical fiber. Distal tip (diameter 0.9 mm, balloon length 30 mm, diameter of inflated balloon at 2 atm-3.0 mm).Although penetration of tissues by visible light (380–740 nm) is less than that of light with greater wavelengths,5 delivery of energy to tissues of interest can be maximized with illumination of the microcatheter balloon (Fig. 1) when inflated. Distension of the balloon may transiently displace pulmonary secretions or mucus (when positioned within the bronchial tree) or blood flow (when positioned within the pulmonary vasculature) and, therefore, reduce energy losses from undesired delivery to nontargeted tissues, cells, or debris.An endobronchial approach is logical, given target-organ access, a somewhat lesser degree of invasiveness, and requisite adjunct equipment relative to an endovascular approach. However, pulmonary arterial access for delivering supplemental therapy intravascularly may be justified for certain patients. Additional intrapulmonary illumination could be performed with blue- and red-light irradiation by this route as well, using the same balloon-assisted microcatheter system.Endoluminal catheter-based phototherapy may aid in the recovery of patients suffering from COVID-19, when implemented as part of a treatment regimen, including medical therapy with antiviral agents or immunomodulators. A system to demonstrate the impact of endoluminal phototherapy for COVID-19 is technically feasible; after confirmation of optimal energy wavelengths, fluency, treatment timing, cycle duration, and other delivery parameters this modality can be functionally demonstrated within a pre-clinical large animal model. After this, a clinical-stage feasibility study will establish a safety and efficacy profile for endoluminal phototherapy of COVID-19.AcknowledgmentsThe authors thank Dr. George Dangas, MD, PhD and Dr. Kevin D. Lye, MD, MBA, for their support in providing guidance to the concepts discussed in this article.Author Disclosure StatementN.N.K. has a patent filed for relevant technology. J.B.H. is the CEO of Colorado Medical Equipment.References1. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061–1069. Crossref, Medline, Google Scholar2. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020:e203786; DOI: 10.1001/jama.2020.3786. Crossref, Google Scholar3. Tsen SW, Chapa T, Beatty W, Xu B, Tsen KT, Achilefu S. Ultrashort pulsed laser treatment inactivates viruses by inhibiting viral replication and transcription in the host nucleus. Antiviral Res 2014;110:70–76. Crossref, Medline, Google Scholar4. Tsen KT, Tsen SW, Chang CL, Hung CF, Wu TC, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Opt 2007;12:064030. Crossref, Medline, Google Scholar5. Enwemekaa T, Bumaha VV, Masson-Meyers DS. Light as a potential treatment for pandemic coronavirus infections: a perspective. J Photochem Photobiol B Biol 2020;207:111891. Crossref, Medline, Google Scholar6. Kipshidze N, Sahota H, Komorowski R, Nikolaychik V, Keelan MHJr. Photoremodeling of arterial wall reduces restenosis after balloon angioplasty in an atherosclerotic rabbit model. J Am Coll Cardiol 1998;31:1152–1157. Crossref, Medline, Google Scholar7. Kipshidze N, Keelan MH, Petersen JR, et al. Photoactivation of vascular iNOS and elevation of cGMP in vivo: possible mechanism for photovasorelaxation and inhibition of restenosis in an atherosclerotic rabbit models. Photochem Photobiol 2000;72:579–582. Crossref, Medline, Google Scholar8. Åkerström S, Mousavi-Jazi M, Klingström J, Leijon M, Lundkvist A, Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol 2005;1966–1969. Crossref, Medline, Google Scholar9. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020; DOI: 10.1056/NEJMoa2015432. Crossref, Google ScholarFiguresReferencesRelatedDetailsCited byPhototherapy and optical waveguides for the treatment of infectionAdvanced Drug Delivery Reviews, Vol. 179 Volume 38Issue 10Oct 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Nicholas N. Kipshidze, Nodar Kipshidze, and Joseph B. Horn.Transcatheter Endoluminal Phototherapy as a Possible Adjunct Treatment for Patients with COVID-19.Photobiomodulation, Photomedicine, and Laser Surgery.Oct 2020.579-580.http://doi.org/10.1089/photob.2020.4884Published in Volume: 38 Issue 10: October 7, 2020Online Ahead of Print:September 18, 2020PDF download