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C.P. Sabino, et al. Journal of Photochemistry & Photobiology, B: Biology 212 (2020) 111999 Table 1 Light-based strategies available to combat the emergence of COVID-19 pandemic. FFR: filtering facepiece respirator. Light-based Platform Natural Ultraviolet Light Ultraviolet Germicidal Irradiation Photoantimicrobials and Photodynamic Therapy Antimicrobial Blue Light Photobiomodulation Therapy Ultrafast Laser Irradiation at low irradiance Potential Applications Surface, FFR reuse, air and water disinfection Environmental and surface disinfection, therapeutics, virus inactivation in biological products Environmental and surface disinfection, therapeutics, virus inactivation in biological materials Therapeutics Selective virus inactivation in blood products, pharmaceuticals, food and vaccine development Advantages Synthesis of vitamin D Microbicidal activity Low exposure time to reach high levels of pathogen inactivation (< 1 min) depending on irradiance of light source Efficient and selective pathogen inactivation following short period of illumination if photosensitizer is resonant to light source wavelength Non-invasive approach Succesfull results in humans with artificial light sources Can be used in inhabited places and to treat infections in humans No notable detrimental effect in materials following long periods of illumination Non-invasive technique Succesfull results in humans with artificial light sources Adjuvant to conventional therapies Selective pathogen inactivation Chemical-free vaccine preparation Disavantages Sunburn following overexposure Long-term aging and cancer risk Risk of tissue damage and cancer Potential long-term degradation of materials Photosensitizer could promote material and/ or tissue staining Systemic PS administration may cause photosensitivity Succesfull results depend on light parameters, type of microorganism, PS concentration and pre-irradiation time Long exposure time (above 30 min) Effect is more pronounced in the presence of exogenous photoabsorbers Succesfull results depend on light parameters, patient characteristics and disease aetiology Long exposure time (3̴ h) Expensive light sources “lung inflammation” [109] OR “ARDS” [112] OR “lung oxidative stress” [113] OR “asthma” [114] many involving small animal models where it can be argued that light penetrates more easily than in hu- mans. Because COVID-19 involves a “cytokine storm”, PBM delivered to the torso (chest and back) might not only allow some light to reach the lungs but might also reduce the systemic inflammation responsible for COVID-19 sepsis-like syndrome [115] and disseminated intravascular coagulation [116] that can be deadly [117]. Moreover, PBM is more effective on hypoxic cells [118], suggesting it could be effective for COVID-19 infection, which seems to be characterized by severe hypoxia [119]. Nevertheless, so far there are no experimental data supporting the influence of PBM on COVID-19. Therefore, clinical studies have to be performed to understand whether PBM therapy may actually reduce the cytokine storm impacts for COVID-19 patients. Hospitalized patients receiving mechanical ventilation or under high-oxygen continuous positive airway pressure (CPAP) treatment could be placed on an LED pad. These do not generate unacceptable levels of heat, so the high fever experienced by these patients should not be a problem. LED-based PBM devices similar to these have been approved by the FDA for general health and wellness applications, and there are no reported adverse effects [120]. However, PBM is not re- commended to be used over cancerous lesions since the effects on tumor cells are not fully understood yet [121]. 9. Ultrafast Laser Irradiation Ultrashort pulse lasers (USPLs) emitting visible to near-infrared light have been used to inactivate a broad spectrum of viruses (human immunodeficiency virus, human papillomavirus, encephalomyocarditis virus, M13 bacteriophage, tobacco mosaic virus, and murine cytome- galovirus) with no damage to human or murine cells [122–126]. Re- gardless of wavelength, ultrafast laser irradiation at low mean irra- diance levels (≤ 1 W/cm2) does not promote ionization effects that could impair host cells. This irradiation does not appear to destroy ei- ther bovine serum albumin or single-stranded DNA, nor cause adverse effects like those produced by toxic or carcinogenic chemicals. Previous works suggest that the antimicrobial effect of USPLs at low mean ir- radiance is exerted via impulsive stimulated Raman scattering, whereby high-frequency resonance vibrations provoke vibrations of sufficient strength to disintegrate the capsid into subunits through the breaking of weak links (e.g., hydrogen bonds and hydrophobic contacts) in non- enveloped viruses [126]. For enveloped virus, USPLs promote vibra- tions on the proteins of the capsid. These excitations break the hy- drogen bonds and hydrophobic contacts causing partial unfolding of the proteins. Since the concentration of confined proteins is very high within the capsid of a virus, they can assemble with other neighboring proteins, leading to the aggregation of proteins [125]. In contrast, an intense laser pulse could generate shock wave-like vibrations upon impact with the virus to promote viral inactivation [126]. However, laser pulsing may not be necessary for its antimicrobial action. Recently, Kingsley et al. applied a tunable mode-locked Ti- Sapphire laser emitting femtosecond pulses at wavelengths of 400, 408, 425, 450, 465, and 510 nm to verify inactivation of murine norovirus (MNV) [92]. Using an average power of 150 mW, authors observed that femtosecond-pulsed light emitting at 408, 425 and 450 nm promoted more than 99.9% of virus inactivation after 3 h of illumination, in- dicating that the inactivation mechanism is not wavelength-specific. In addition, they reported that a continuous wave 408 nm laser at similar power also promoted reduction of plaque-forming units, although the addition of exogenous photosensitizers has increased MNV inactivation. These data suggest that virus inactivation does not require pulsing and can be improved in the presence of singlet oxygen enhancers, as pre- viously reported for aBL (see section 7). Potential use of USPLs encompasses the inactivation of pathogens in pharmaceuticals, blood products and uncooked foods as well as che- mical-free whole inactivated virus vaccine preparation [127,128]. Laser treatment resulted in 1-log, 2-log, and 3-log reductions in hepatitis A, human immunodeficiency, and murine cytomegalovirus, respectively, in human plasma with no changes in the structure of fibrinogen [127]. Further, in mice USPL-induced inactivation of H1N1 influenza virus was more effective than formalin and did not cause damage to viral surface proteins or resulted in the production of carbonyl groups in proteins [128]. Concluding remarks As we presented in this review, light-based technologies have un- ique features that could be useful to face the COVID-19 pandemic, but could also present pitfalls that deserve to be highlighted. Thus, we compiled at Table 1 their advantages and disadvantages. In summary, we have described how light-based strategies can be used to reduce SARS-CoV-2 transmission through air, water, and 5PDF Image | A Light-based technologies for management of COVID-19 pandemic
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