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 Table of Contents  
FUTURE TRENDS
Year : 2020  |  Volume : 6  |  Issue : 2  |  Page : 156-158

Could tracheo-bronchial ultraviolet C irradiation be a valuable adjunct in the management of severe COVID-19 pulmonary infections?


Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA

Date of Submission23-Mar-2020
Date of Acceptance05-Apr-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
Dr. Stanislaw P Stawicki
Department of Research and Innovation, St. Luke's University Health Network, 801 Ostrum Street, Bethlehem, Pennsylvania 18015
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_19_20

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  Abstract 


The coronavirus pandemic is wreaking havoc as it mercilessly devastates communities around the world, disproportionately affecting the most vulnerable populations. Thus far, other than high-acuity mechanical ventilatory support and traditional critical care management strategies, there are no proven or effective ways of lessening the impact of COVID-19 pulmonary infection and the associated acute respiratory distress syndrome. This article outlines a proposal for repeated short-term tracheo-bronchial application of ultraviolet C irradiation as a potential adjunctive treatment option for tracheally intubated patients suffering from severe COVID-19 infections.
The following core competencies are addressed in this article: Medical knowledge, Patient care.

Keywords: Acute respiratory distress syndrome, COVID-19, endobronchial therapy, respiratory failure, SARS-CoV-2 pandemic, tracheo-bronchial therapy, ultraviolet C, ultraviolet light therapy


How to cite this article:
Stawicki SP. Could tracheo-bronchial ultraviolet C irradiation be a valuable adjunct in the management of severe COVID-19 pulmonary infections?. Int J Acad Med 2020;6:156-8

How to cite this URL:
Stawicki SP. Could tracheo-bronchial ultraviolet C irradiation be a valuable adjunct in the management of severe COVID-19 pulmonary infections?. Int J Acad Med [serial online] 2020 [cited 2020 Sep 24];6:156-8. Available from: http://www.ijam-web.org/text.asp?2020/6/2/156/287946




  Introduction Top


The coronavirus pandemic is wreaking havoc as it mercilessly rolls through our communities, cities, countries, and continents. Extreme social isolation measures have been able to slow the spread of the disease, but lack of effective therapies means that the most vulnerable among us – the elderly and those with preexisting medical conditions – continue to be disproportionately affected by the most severe, and most deadly, pulmonary manifestations of COVID-19.

Thus far, other than high-acuity mechanical ventilatory support and traditional critical care management strategies, there are no proven or effective ways of lessening the impact of COVID-19 pulmonary infection (PI) and the associated acute respiratory distress syndrome (ARDS). Consequently, urgent research and application of new and innovative ways of treating COVID-19 PI will be needed. In parallel to pharmacological and supportive management strategies, local application of antiviral treatments may provide a potentially important avenue in our fight against SARS-CoV-2. The current article explores the concept of ultraviolet C (UVC) irradiation, a previously described antimicrobial treatment modality,[1],[2] via direct UVC illumination of the tracheo-bronchial tree of tracheally intubated COVID-19 patients. Although UVC (wavelength range, 100-280 nm) radiation is the focus of our current discussion, the application of UVA (315-320 nm to 400 nm) and UVB (280-289 nm to 315-320 nm) is also feasible, albeit with lower antimicrobial effectiveness. It is assumed by the author that UVA or UVB can be readily substituted for UVC radiation, with any such interchangeability determined by risk-benefit profile and clinical applicability of each potential therapuetic option.


  Coronavirus Sensitivity to Ultraviolet Radiation Top


It is well established that coronaviruses in general are very sensitive to ultraviolet radiation (UVR).[3],[4] In fact, coronaviruses appear to be more sensitive to UVR than other viruses,[5],[6],[7],[8] thus opening a way of potentially employing physicochemical treatments against SARS-CoV-2, including direct tracheo-bronchial UVR application (TBUA). In one study, the SARS-CoV was inactivated by UVR at 254 nm (UVC or 200–280 nm), which is absorbed by RNA and DNA bases, with partial viral inactivation at 1 min and increasing efficiency up to 6 min.[9] There was a resultant 400-fold decrease in infectious virus, with no additional inactivation seen between 6 and 10 min of UVC exposure.[9]


  Proposal for Tracheo-Bronchial Ultraviolet C (UVC) Radiation Application Top


Although not proven in thein vivo setting, the author of this communication would like to propose that intubated patients with pulmonary manifestations of COVID-19 be considered for a clinical trial of repeated, 6-min (360-s) treatments of TBUA using UVC light, utilizing diffusive optical fiber conduits for photodynamic therapy, or comparative delivery platform(s).[10],[11] In addition, direct bronchoscopic application of UVC, dependent on the conductivity of the fiberoptic core of the bronchoscope, could also be considered in patients who are able to clinically tolerate such maneuver. Under the proposed TBUA protocol, the optimal scenario would involve advancing two diffusive fiberoptic cables into the tracheo-bronchial tree, into each of the mainstem bronchi (or even more selectively into targeted lung segments, if feasible). Based on the available tissue culture infection dose (TCID) data, it is assumed for our purposes that tissue SARS-CoV-2 levels will increase by two orders of magnitude every 4–6 h.[12] Thus, the proposed treatment would need to be re-applied every 4 h, on an average. Recognizing that prolonged or excessive UVC (and to a lesser extent UVB and UVA) radiation exposure can lead to deleterious changes in human cells,[2],[13],[14] the intensity of TBUA will be limited to between 2.0 and 2.5 mW,[2],[15],[16],[17] with appropriate modifications as required per ongoing patient safety and efficacy observations. Based on viral replication characteristics, the therapy should be applied for 24 h (up to six treatments) and then re-assessed for continuation versus discontinuation based on patient response and clinical status, any patient safety concerns, as well as the judgment of the treating physician. During the therapeutic application, appropriate occupational safety standards, including proper eye and skin protection, should be utilized by all participating providers.[15] Based on data derived from studies on human nasal mucosa, intermittent, localized, limited-duration UVR application is well tolerated, and the exposed mucosal tissues are capable of efficient repair of UVR-induced DNA damage.[2] Schematic representation of the proposed therapeutic regimen and configuration is shown in [Figure 1].
Figure 1: Schematic representation of UVC-based direct tracheo-bronchial UVR applications: (a) Appropriate UVC source with a fiberoptic adapter; (b) direct bronchoscopic application of UVC; (c) placement of indwelling diffusive optical fiber conduits, terminating in mainstem bronchi bilaterally. Note that radiation intensity should be limited to not more than 2.5 mW and that treatments should be applied every 4 h, with at least 24 h of therapy before reassessment. Discontinuation of treatment should be determined by the treating physician, after considering: (a) the status of patient condition and (b) the safety and efficacy of the treatment. Note: UVB (280-289 nm to 315-320 nm) or UVA (314-320 nm to 400 nm) can be used interchangeably with UVC within the proposed framework. UVR = Ultraviolet radiation, UVA = Ultraviolet A, UVB = Ultraviolet B, UVC = Ultraviolet C

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  Conclusion Top


The current proposal is based on the conjunction of known scientific facts, established coronavirus characteristics, and the relatively minimally invasive nature of the conceptual paradigm. Although purely hypothetical and by no means proven, TBUA featuring repeated short-term applications of UVC may be feasible and should be considered in the context of therapeutic clinical trial(s). The risk–benefit of proceeding with the current proposal seems very reasonable, especially when considering the disproportionately high mortality of COVID-19 PI, specifically among patients suffering from ARDS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

The author of this manuscript attests that the work presented is intended solely as hypothesis-generating contribution, did not involve any human or animal research, and thus does not require Institutional Review Board/Ethics Committee review.

Intellectual property considerations

The author would like to make this concept available, free of royalties or other restrictive considerations, to all those interested in designing and implementing any and all derivations of the framework proposed herein. Consequently, this published work shall be considered “prior art” to ensure that no commercial barriers to entry exist within the extraordinary context of the COVID-19 pandemic. Intellectual and technical content within this manuscript is therefore being distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.



 
  References Top

1.
Dai T, Vrahas MS, Murray CK, Hamblin MR. Ultraviolet C irradiation: An alternative antimicrobial approach to localized infections?. Expert review of anti-infective therapy 2012;10:185-95.  Back to cited text no. 1
    
2.
Mitchell D, Paniker L, Sanchez G, Bella Z, Garaczi E, Szell M, et al. Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation. Journal of cellular and molecular medicine 2010;14:313-22.  Back to cited text no. 2
    
3.
Hindawi SI, Hashem AM, Damanhouri GA, El-Kafrawy SA, Tolah AM, Hassan AM, et al. Inactivation of Middle East respiratory syndrome-coronavirus in human plasma using amotosalen and ultraviolet A light. Transfusion 2018;58:52-9.  Back to cited text no. 3
    
4.
Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, Müller TH, et al. 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. Transfusion 2018;58:2202-7.  Back to cited text no. 4
    
5.
Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB, et al. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. World J Pediat 2020;5:1-7.  Back to cited text no. 5
    
6.
Hashem A, Hassan AM, Tolah AM, Alsaadi MA, Abunada Q, Damanhouri GA, et al. Amotosalen and ultraviolet A light efficiently inactivate MERS-coronavirus in human platelet concentrates. Trans Med 2019;29:434-41.  Back to cited text no. 6
    
7.
Momattin H, Al-Ali AY, Al-Tawfiq JA. A systematic review of therapeutic agents for the treatment of the Middle East respiratory syndrome coronavirus (MERS-CoV). Travel Med Infect Dis 2019;30:9-18.  Back to cited text no. 7
    
8.
Ansaldi F, Banfi F, Morelli P, Valle L, Durando P, Sticchi L, et al. SARS CoV, influenza A and syncitial respiratory virus resistance against common disinfectants and ultraviolet irradiation. J Prev Med Hygiene 2004;45:5-8.  Back to cited text no. 8
    
9.
Darnell ME, Subbarao K, Feinstone SM, Taylor DR. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods 2004;121:85-91.  Back to cited text no. 9
    
10.
Hasselgren L, Galt S, Hard S. Diffusive optical fiber ends for photodynamic therapy: Manufacture and analysis. Appl Optics 1990;29:4481-8.  Back to cited text no. 10
    
11.
Dai T, Vrahas MS, Murray CK, Hamblin MR. Ultraviolet C irradiation: An alternative antimicrobial approach to localized infections? Exp Rev Anti Infect Ther 2012;10:185-95.  Back to cited text no. 11
    
12.
Hagemeijer, MC, Verheije MH, Ulasli M, Shaltiël IA, de Vries LA, Reggiori F, et al. Dynamics of coronavirus replication-transcription complexes. J Virol 2010;84:2134-49.  Back to cited text no. 12
    
13.
HPS. Answer to Question #9450 in Category: Ultraviolet Radiation; March, 23 2020. Available from: https://hps.org/publicinformation/ate/q9450.html. [Last accessed on 2020 Mar 26].  Back to cited text no. 13
    
14.
Oxidation_Technologies_LLC. Ozone Production from UV: How does a UV Lamp Ozone Generator Work? 23 March, 2020. Available from: https://www.oxidationtech.com/ozone/ozone-production/uv-lamp.html. [Last accessed on 2020 Mar 26].  Back to cited text no. 14
    
15.
CCOHS. OSH Answers Fact Sheets: Ultraviolet Radiation. 23 March, 2020. Available from: https://www.ccohs.ca/oshanswers/phys_agents/ultravioletradiation.html. [Last accessed on 2020 Mar 26].  Back to cited text no. 15
    
16.
Bäumler W. Light sources for photodynamic therapy and fluorescence diagnosis in dermatology. Comprehensive Series in Photoscience. Vol. 1. Amsterdam, The Netherlands: Elsevier; 2001. p. 83-98.  Back to cited text no. 16
    
17.
Heier SK, Rothman KA, Heier LM, Rosenthal WS. Photodynamic therapy for obstructing esophageal cancer: Light dosimetry and randomized comparison with Nd: YAG laser therapy. Gastroenterology 1995;109:63-72.  Back to cited text no. 17
    


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