A Potential Role for Photobiomodulation Therapy in Disease Treatment and Prevention in the Era of COVID-19
Ann Liebert1,2,3,*, Brian Bicknell4,3, Wayne Markman5,3, Hosen Kiat6,7,8
1Faculty of Medicine and Health, University of Sydney, Sydney, Australia. 2Research and Governance, Adventist Hospital Group, Wahroonga, Australia. 3SYMBYX Pty Ltd, Artarmon, Australia. 4Faculty of Health Science, Australian Catholic University, North Sydney, Australia. 5School of Business, University of Technology, Sydney, Australia. 6Cardiac Health Institute, Sydney, Australia. 7Faculty of Medicine, University of NSW, Kensington, Australia. 8Faculty of Medicine, health and Human Sciences, Macquarie University, Macquarie Park, Australia
COVID-19 is an evolving pandemic that has far reaching global effects, with a combination of factors that makes the virus difficult to contain. The symptoms of infection can be devastating or at the least very debilitating for vulnerable individuals. It is clear that the elderly are at most risk of the adverse impacts of the virus, including hospitalization and death. Others at risk are those with comorbidities such as cardiovascular disease and metabolic conditions and those with a hyper-excitable immune response. Treatment options for those with acute responses to the virus are limited and there is an urgent need for potential strategies that can mitigate these severe effects. One potential avenue for treatment that has not been explored is the microbiome gut/lung axis. In addition to those severely affected by their acute reaction to the virus, there is also a need for treatment options for those that are slow to recover from the effects of the infection and also those who have been adversely affected by the measures put in place to arrest the spread of the virus. One potential treatment option is photobiomodulation (PBM) therapy. PBM has been shown over many years to be a safe, effective, non-invasive and easily deployed adjunctive treatment option for inflammatory conditions, pain, tissue healing and cellular energy. We have also recently demonstrated the effectiveness of PBM to alter the gut microbiome. PBM therapy is worthy of consideration as a potential treatment for those most vulnerable to COVID-19, such as the elderly and those with comorbidities. The treatment may potentially be advantageous for those infected with the virus, those who have a slow recovery from the effects of the virus and those who have been denied their normal exercise/rehabilitation programs due to the isolation restrictions that have been imposed to control the COVID-19 pandemic.
Liebert Ann,Bicknell Brian,Markman Wayne, et al. A Potential Role for Photobiomodulation Therapy in Disease Treatment and Prevention in the Era of COVID-19[J]. Aging and disease,
2020, 11(6): 1352-1362.
Figure 1. Conditions that have been shown to be successfully treated using photobiomodulation therapy.
Zhang R, Li Y, Zhang AL, Wang Y, Molina MJ (2020). Identifying airborne transmission as the dominant route for the spread of COVID-19. Proc Natl Acad of Sci, 117:14857-14863.
Guo J, Huang Z, Lin L, Lv J (2020). Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Am Heart Assoc, 9:e016219.
Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. (2020). The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med, 172:577-582.
Wu Z, McGoogan JM (2020). Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 323:1239-1242.
Barzilai N, Appleby JC, Austad SN, Cuervo AM, Kaeberlein M, Gonzalez-Billault C, et al. (2020). Geroscience in the Age of COVID-19. Aging Dis, 11:2.
Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C (2020). Cardiac and arrhythmic complications in patients with COVID-19. J Cardiovasc Electrophysiol, 31:1003-1008.
Picca A, Lezza AMS, Leeuwenburgh C, Pesce V, Calvani R, Landi F, et al. (2017). Fueling inflamm-aging through mitochondrial dysfunction: mechanisms and molecular targets. Int J Mol Sci, 18:933.
Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. (2020). COVID-19 and cardiovascular disease. Circulation, 141:1648-1655.
Filardi T, Morano S (2020). COVID-19: is there a link between the course of infection and pharmacological agents in diabetes? J Endocrinol Invest:1-8.
Jordan RE, Adab P, Cheng K2020. Covid-19: risk factors for severe disease and death. Bri Med J, 368:m1198
Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. (2020). Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol, 21:335-337.
Rebelos E, Moriconi D, Virdis A, Taddei S, Foschi D, Nannipieri M (2020). Importance of metabolic health in the era of COVID-19. Metabolism, 108:154247.
Finer N, Garnett SP, Bruun JM (2020). COVID-19 and obesity. Clin Obes, 10:e12365.
Butler MJ, Barrientos RM (2020). The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun, 87:53-54
Saghazadeh A, Rezaei N (2020). Immune-epidemiological parameters of the novel coronavirus-a perspective. Expert Rev Clin Immunol, 16:465-470.
Cheng J, Wen J, Wang N, Wang C, Xu Q, Yang Y (2019). Ion channels and vascular diseases. Arterioscler Thromb and Vasc Biol, 39:e146-e156.
Karpinski RI, Kinase Kolb AM, Tetreault NA, Borowski TB (2018). High intelligence: A risk factor for psychological and physiological overexcitabilities. Intelligence, 66:8-23.
Kursumovic E, Lennane S, Cook TM (2020). Deaths in healthcare workers due to COVID-19: the need for robust data and analysis. Anaesth, 75:989-992.
Roy S (2020). Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on Hydroxychloroquine and Azithromycin Combination. SN Compr Clin Med, 2:1019-1024.
Stone E, Kiat H, McLachlan CS (2020). Atrial fibrillation in COVID-19: A review of possible mechanisms. FASEB J, 34,9:11347-11354
Asadi-Pooya AA, Simani L (2020). Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci, Jun 15:116832.
Jahanshahlu L, Rezaei N (2020). Central Nervous System Involvement in COVID-19. Arch Med Res, May 22:S0188-4409(20)30797-9
Didangelos A (2020). COVID-19 Hyperinflammation: What about Neutrophils? mSphere, 5:e00367-00320.
Schett G, Sticherling M, Neurath MF (2020). COVID-19: risk for cytokine targeting in chronic inflammatory diseases? Nat Rev Immunol, 20:271-272.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 395:1033-1034.
Carfì A, Bernabei R, Landi F (2020). Persistent symptoms in patients after acute covid-19. JAMA, 324:603-605.
Varatharaj A, Thomas N, Ellul MA, Davies NW, Pollak TA, Tenorio EL, et al. (2020). Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry, Jun 25:S2215-0366(20)30287-X.
Islam MF, Cotler J, Jason LA (2020). Post-viral fatigue and COVID-19: lessons from past epidemics. Fatigue, 8:61-69.
Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, et al. (2020). Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry, 7:611-627.
Dalakas MC (2020). Guillain-Barré syndrome: The first documented COVID-19-triggered autoimmune neurologic disease. Neurol Neuroimmunol Neuroinflamm, 7:e781.
Schippers M, Kompanje E (2020). For the Greater Good? The Devastating Ripple Effects of the Covid-19 Crisis. The Devastating Ripple Effects of the Covid-19 Crisis https://ideas.repec.org/p/ems/eureri/127236.html.
Khosrawipour V, Lau H, Khosrawipour T, Kocbach P, Ichii H, Bania J, et al. (2020). Failure in initial stage containment of global COVID-19 epicenters. J Med Virol, 92:863-867.
Mahase E (2020). Covid-19: what treatments are being investigated? Bri Med J, 368:m1252.
Dhar D, Mohanty A (2020). Gut microbiota and Covid-19- possible link and implications. Virus Res, 285:198018-198018.
Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011). Human nutrition, the gut microbiome, and immune system: envisioning the future. Nature, 474:327.
Zheng D, Liwinski T, Elinav E (2020). Interaction between microbiota and immunity in health and disease. Cell Res, 30:492-506.
Marsland BJ, Trompette A, Gollwitzer ES (2015). The gut-lung axis in respiratory disease. Ann Am Thorac Soc, 12:S150-S156.
Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. (2020). Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology, May 20:S0016-5085(20)34701-6
Lazar V, Ditu L-M, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, et al. (2018). Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. Front Immunol, 9:1830.
Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, et al. (2014). Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med, 20:159-166.
Osamu K, Akira A, Sazaly A, Naoki Y (2018). Probiotics and Paraprobiotics in Viral Infection: Clinical Application and Effects on the Innate and Acquired Immune Systems. Curr Pharm Des, 24:710-717.
Cole-Jeffrey CT, Liu M, Katovich MJ, Raizada MK, Shenoy V (2015). ACE2 and microbiota: emerging targets for cardiopulmonary disease therapy. J Cardiovasc Pharmacol, 66:540.
Idris A, Hasnain SZ, Huat LZ, Koh D (2017). Human diseases, immunity and the oral microbiota—Insights gained from metagenomic studies. Oral Sci Int, 14:27-32.
Kumar PS (2017). From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J Physiol, 595:465-476.
Ma W-T, Pang M, Fan Q-L, Chen D-K (2019). The commensal microbiota and viral infection: a comprehensive review. Front Immunol, 10:1551.
Pitones-Rubio V, Chávez-Cortez EG, Hurtado-Camarena A, González-Rascón A, Serafín-Higuera N (2020). Is periodontal disease a risk factor for severe COVID-19 illness? Med Hypotheses, 144:109969.
Patel J, Sampson V (2020). The role of oral bacteria in COVID-19. Lancet Microbe, 1:e105.
Kandolf-Sekulovic L, Kataranovski M, Pavlovic MD (2003). Immunomodulatory effects of low-intensity near-infrared laser irradiation on contact hypersensitivity reaction. Photodermatol, Photoimmunol Photomed, 19:203-212.
Toma RL, Oliveira MX, Renno ACM, Laakso E-L (2018). Photobiomodulation (PBM) therapy at 904 nm mitigates effects of exercise-induced skeletal muscle fatigue in young women. Lasers Med Sci, 33:1197-1205.
Ferraresi C, Huang YY, Hamblin MR (2016). Photobiomodulation in human muscle tissue: an advantage in sports performance? J Biophotonics, 9:1273-1299.
Trajano LAdSN, Stumbo AC, Da Silva CL, Mencalha AL, Fonseca AS (2016). Low-level infrared laser modulates muscle repair and chromosome stabilization genes in myoblasts. Lasers Med Sci, 31:1161-1167.
de Brito A, Alves AN, Ribeiro BG, Barbosa DVDE, Magalhaes EMR, Fernandes KPS, et al. (2018). Effect of photobiomodulation on connective tissue remodeling and regeneration of skeletal muscle in elderly rats. Lasers Med Sci, 33:513-521.
Rodrigues NC, Brunelli R, de Araújo HSS, Parizotto NA, Renno ACM (2013). Low-level laser therapy (LLLT)(660 nm) alters gene expression during muscle healing in rats. J Photochem Photobiol B, 120:29-35.
de Souza GHM, Ferraresi C, Moreno MA, Pessoa BV, Damiani APM, Gasparotto Filho V, et al. (2020). Acute effects of photobiomodulation therapy applied to respiratory muscles of chronic obstructive pulmonary disease patients: a double-blind, randomized, placebo-controlled crossover trial. Lasers Med Sci, 35:1055-1063.
Prolla TA, Denu JM (2014). NAD+ deficiency in age-related mitochondrial dysfunction. Cell Met, 19:178-180.
Mitrofanis J, Jeffery G (2018). Does photobiomodulation influence ageing? Aging, 10:2224-2225.
de Freitas LF, Hamblin MR (2016). Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE J Sel Top Quantum Electron, 22:7000417.
Manchini MT, Serra AJ, dos Santos Feliciano R, Santana ET, Antonio EL, de Carvalho PdTC, et al. (2014). Amelioration of cardiac function and activation of anti-inflammatory vasoactive peptides expression in the rat myocardium by low level laser therapy. PLoS One, 9:e101270.
Liebert A, Krause A, Goonetilleke N, Bicknell B, Kiat H (2017). A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms. Sci Rep, 7:42386.
Wang X, Tian F, Soni SS, Gonzalez-Lima F, Liu H (2016). Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser. Sci Rep, 6:30540.
Zomorrodi R, Loheswaran G, Pushparaj A, Lim L (2019). Pulsed near infrared transcranial and intranasal photobiomodulation significantly modulates neural oscillations: a pilot exploratory study. Sc Rep, 9:6309.
da Silva MM, Albertini R, de Carvalho PdTC, Leal-Junior ECP, Bussadori SK, Vieira SS, et al. (2018). Randomized, blinded, controlled trial on effectiveness of photobiomodulation therapy and exercise training in the fibromyalgia treatment. Lasers Med Sci, 33:343-351.
Hamblin MR (2017). Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys, 4:337-361.
Laakso L, Cramond T, Richardson C, Galligan JP (1994). Plasma ACTH and betaendorphin levels in response to low level laser therapy (LLLT) in myofascial trigger points. Laser Ther, 6:133-142.
Scholzen TE, Ko¨nig S, Fastrich M, Bo¨hm M, Luger TA (2007). Terminating the stress: peripheral peptidolysis of proopiomelanocortin-derived regulatory hormones by the dermal microvascular endothelial cell extracellular peptidases neprilysin and angiotensin-converting enzyme. Endocrinology, 148:2793-2805.
Cerdeira CD, Lima Brigagão MRP, Carli ML, de Souza Ferreira C, de Oliveira Isac MoraesG, Hadad H, et al. (2016). Low-level laser therapy stimulates the oxidative burst in human neutrophils and increases their fungicidal capacity. J Biophotonics, 9:1180-1188.
Neubert E, Bach K, Busse J, Bogeski I, Schön MP, Kruss S, et al. (2019). Blue and long-wave ultraviolet light induce in vitro Neutrophil Extracellular Trap (NET) formation. Front Immunol, 10:2428.
Aimbire F, De Oliveira AL, Albertini R, Correa J, De Campos CL, Lyon J, et al. (2008). Low level laser therapy (LLLT) decreases pulmonary microvascular leakage, neutrophil influx and IL-1β levels in airway and lung from rat subjected to LPS-induced inflammation. Inflammation, 31:189.
de Brito Sousa K, Rodrigues M, de Souza Santos D, Mesquita-Ferrari RA, Nunes FD, de Fátima Teixeira da SilvaD, et al. (2020). Differential expression of inflammatory and anti-inflammatory mediators by M1 and M2 macrophages after photobiomodulation with red or infrared lasers. Lasers Med Sci, 35:337-343.
Tolentino M, Cho CC, Lyons J-A (2019). Photobiomodulation therapy (PBMT) regulates the production of IL-10 and IFN-Ɣ by peripheral blood mononuclear cells (PBMC) and CD4+ T cells isolated from subjects with Multiple Sclerosis (MS). J Immunol, 202(1 Supp):193.16.
Tolentino M, Cho CC, Lyons J-A (2020). Photobiomodulation (PBM) regulates nitric oxide (NO) production by peripheral blood mononuclear cells (PBMC) isolated from Multiple Sclerosis (MS) patients. J Immunol, 204:160.8.
Brochetti RA, Leal MP, Rodrigues R, Da Palma RK, de Oliveira LVF, Horliana ACRT, et al. (2017). Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice. Lasers Med Sci, 32:1825-1834.
de Lima FM, Villaverde A, Albertini R, Corrêa J, Carvalho R, Munin E, et al. (2011). Dual Effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: Action on anti-and pro-inflammatory cytokines. Lasers Surg Med, 43:410-420.
Yu W, Chi LH, Naim JO, Lanzafame RJ (1997). Improvement of host response to sepsis by photobiomodulation. Lasers Med Sci, 21:262-268.
Assis L, Tim C, Magri A, Fernandes KR, Vassão PG, Renno ACM (2018). Interleukin-10 and collagen type II immunoexpression are modulated by photobiomodulation associated to aerobic and aquatic exercises in an experimental model of osteoarthritis. Lasers Med Sci, 33:1875-1882.
Stadler I, Evans R, Kolb B, Naim JO, Narayan V, Buehner N, et al. (2000). In vitro effects of low-level laser irradiation at 660 nm on peripheral blood lymphocytes. Lasers Surg Med, 27:255-261.
Meldrum DR, Ayala A, Chaudry IH (1994). Energetics of lymphocyte" burnout" in late sepsis: adjuvant treatment with ATP-MgCl2 improves energetics and decreases lethality. J Surg Res, 56:537-542.
Karu T (1989). Photobiology of low-power laser effects. Health Phys, 56:691-704.
Yu W, McGowan M, Naim J, Lanzafame R 1996. Mechanism of low level laser biostimulatory effects. In 16th Annual Meeting. American Society for Laser Medicine and Surgery. Lake Buena Vista, Florida (April 15-17, 1996).
Mafra de Lima F (2013). Low-level laser therapy restores the oxidative stress balance in acute lung injury induced by gut ischemia and reperfusion. Photochem and Photobiol, 89:179-188.
De Brito Léia AA, Herculano KZ, Santos TG, Rigonato-Oliveira NC, Alves CE, Palma RK, et al. (2019). Effect of photobiomodulation on inflammation and production of TGF-ß in experimental model of pulmonary fibrosis. Eur Respir J, 54:PA5199.
da Cunha Moraes G, Vitoretti LB, de Brito AA, Alves CE, de Oliveira NCR, dos Santos Dias A, et al. (2018). Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor. Oxid Med Cell Longev, 2018:6798238.
Kent AL, Broom M, Parr V, Essex RW, Abdel-Latif ME, Dahlstrom JE, et al. (2015). A safety and feasibility study of the use of 670[thinsp]nm red light in premature neonates. J Perinat, 35:493-496.
Gunn C (2005). Acute respiratory distress syndrome successfully treated with low level laser therapy. J Complement Integr Med, 2:1
Bicknell B, Liebert A, Johnstone D, Kiat H (2018). Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases. Lasers Med Sci, 34:317-327.
Rooks MG, Garrett WS (2016). Gut microbiota, metabolites and host immunity. Nat Rev Immunol, 16:341-352.
Hamblin MR (2016). Shining light on the head: photobiomodulation for brain disorders. BBA Clin, 6:113-124.
El Khoury H, Mitrofanis J, Henderson LA (2019). Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging. Neuroscience, 422:161-171.
Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin MR, et al. (2014). Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. J Neurotrauma, 31:1008-1017.
Schiffer F, Johnston AL, Ravichandran CT, Polcari A, Teicher MH, Webb RH, et al. (2009). Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct, 5:46
Buchaim RL, Barbalho SM, Hamzé AL, de Alvares Goulartoulart R, Rocha KTP, Reis CHB, et al. (2020). Loss of smell and COVID-19: Anatomical and physiological considerations. Int J Adv Eng Res Sci, 7:278-280.
Fernandes AB, Lima CJd, Villaverde AGB, Pereira PC, Carvalho HC, Zângaro RA (2020). Photobiomodulation: Shining Light on COVID-19. Photobiomodul Photomed and Laser Surg, 38:395-397.
Domínguez A, Velásquez SA, David MA (2020). Can Transdermal Photobiomodulation Help Us at the Time of COVID-19? Photobiomodul Photomed Laser Surg, 38:258-259.
Fekrazad R2020. Photobiomodulation and antiviral photodynamic therapy as a possible novel approach in COVID-19 management. Photobiomodul, Photomed, and Laser Surg, 38:255-257.
Sigman SA, Soheila M, Monica M, Vetrici MA (2020). A 57-Year-Old African American Man with Severe COVID-19 Pneumonia Who Responded to Supportive Photobiomodulation Therapy (PBMT): First Use of PBMT in COVID-19. Am J Case Rep, 21:e926779.
Derhovanessian E, Pawelec G (2012). Vaccination in the elderly. Microb Biotechnol, 5:226-232.
Kashiwagi S, Yuan J, Forbes B, Hibert ML, Lee EL, Whicher L, et al. (2013). Near-infrared laser adjuvant for influenza vaccine. PloS One, 8:e82899.
Nir Barzilai, James C Appleby, Steven N Austad, Ana Maria Cuervo, Matt Kaeberlein, Christian Gonzalez-Billault, Stephanie Lederman, Ilia Stambler, Felipe Sierra. Geroscience in the Age of COVID-19[J]. Aging and disease, 2020, 11(4): 725-729.