Table 1.

Articles selected according to the eligibility criteria.

Reference	Type of Article	Human/Animal	Intervention	Results	Conclusions
Wajih et al., 2021 [28]	Experimental, in vitro research	Human blood	Evaluation of nitrite, extreme red light, and its combination on various measures of blood clotting using a variety of agonists. Platelet-rich plasma turbidity assays, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, platelet aggregometry based on multiple impedance, and evaluation of platelet adhesion to collagen coated flow-through microslides.	The combination of extreme red light and nitrite treatment decreased the coagulation measures, but in some cases, the mono-treatment with nitrite or light alone showed no effects. It was observed that platelet adhesions were inhibited by the combination of nitrite and light treatment, while nitrite alone and extreme red light alone led to decreased adhesion.	These results support the potential of the combined treatment of extreme red light and nitrite for the prevention of thrombosis in extracorporeal devices or with shallow-tissue depth, where extreme red light can penetrate. Given the role of thrombosis in COVID-19, application to the treatment of patients infected with SARS-Cov-2 can also be considered.
Enwemeka et al., 2020 [29]	Perspective study	Not applicable	This study relates phototherapy throughout history, initially called heliotherapy, where sunlight was used as a treatment for various diseases, which was of great help in the 1918 pandemic against the Spanish flu. It also reports the beneficial effect of blue/violet light, red and infrared light. With the development of lasers and the evolution of phototherapy, laser therapy originated and is currently called photobiomodulation.	It was observed inactivation of many viruses, including the common flu coronavirus, and antimicrobial effect. Red and infrared light have important therapeutic value, as they are effective in the treatment of various diseases, reducing, for example, inflammation and fibrosis in the lung.	Blue/violet light has potential use in treatments, mitigating opportunistic bacteria, and aiding in hygiene. The effects of red light are effective in treating complications of COVID-19, such as inflammation, pulmonary edema, pneumonia, and acute respiratory distress syndrome (ARDS), which are its leading causes of death.
Razzaghi and Kamani, 2020 [30]	In vitro study	Human	The authors defend the use of the blue laser, which has antimicrobial and anti-inflammatory effects, positive for the immune system. Blood irradiation has a positive influence on the release of hemoglobin nitric oxide (HbNO), with antibacterial effects. This can be used for Photodynamic Therapy (PDT) in combination with Riboflavin as a photosensitizer in order to reduce inflammation of the lungs, increase the amount of nitric oxygen, which will increase the body’s immunity, and improve the supply of oxygen to the blood and tissues, used as a treatment for COVID-19.	It has been observed that LED light has an antiviral effect and that nitric oxide production is the key to many of the capabilities and characteristics of immune cells, such as dendritic cells, Natural Killer cells (NKs exterminators), mast cells, macrophages and other phagocytes and has a cytotoxic and cytoprotective, antiviral effect, antimicrobial, stimulating and suppressing the immune system.	With the results on blue light and the effects of nitric oxide on the immune system along with the emergence of a treatment for COVID-19, the authors discussed a preventive approach using these devices. The form and possible beneficial effects for the treatment of COVID-19 have been described for a laboratory study to be carried out.
Kamani, 2020 [31]	In vivo study	Human	In this study, this was associated with the LLLT and acupuncture technique. The yellow laser light increases Vitamin D and serotonin levels through application to the nose and acupuncture points. The laser acupuncture method has been irradiated perpendicularly to the top of the skin and is a safer way than taking Vitamin D tablets.	The results were different at different acupuncture points. For example, at LR14, activation of the temporal cortexes, frontal cortex, right parietal cortex, and deactivation in the temporal cortex in the bilateral superior temporal gyrus and the limbic cortex. In KI3, there was no significant activation or deactivation.	The author took a preventive approach recognizing the properties of light and studies in this area and its possibility of becoming a treatment for COVID-19.
Pinto et al., 2020 [32]	Experimental, in vivo research	Animal/mice	This study aimed to characterize the PDT associated with the phototherapeutic agent Phthalomethyl D in the process of immunological improvement, cure and repair against SARS-CoV-2. The study used 69 rats submitted to surgery for viral induction and separated into two groups, one treated with ILIB laser and the other with this technique added to the association of Phthalomethyl D.	As a result, both groups achieved a high rate of partial incision closure and acute inflammatory control. In the group treated with the ILIB technique associated with Phthalomethyl D, there was a greater amount of fundamental amorphous substance, fibrocytes, fibroblasts, and giant cells, and the number of keratinocytes, the amount of keratin and the epidermal thickness was reduced concerning the group treated only with the ILIB technique.	Thus, with positive results using the ILIB technique associated with Phthalomethyl D, which obtained satisfactory results in increasing healing, repair, and immunomodulation during viral infection, contributing to the anti-inflammatory response, the use of this treatment in the approach to SARS-CoV-2 is possible.
Mokmeli and Vetrici, 2020 [33]	Study based on clinical experience, peer-reviewed studies and solid laboratory data in experimental animal models.	Not applicable	This study aimed to provide a protocol for the use of low-level laser therapy (LLLT) to prevent disease progression, minimize the time required to use a ventilator, improve healing and shorten recovery time. This technique was chosen because it has strong anti-inflammatory effects and attenuates the cytokine storm and being a safe, effective, low-cost technique with no side effects.	LLLT has therapeutic potential for the respiratory syndrome, with the ability to reduce pain and heal wounds in health areas. In addition, it is also used to treat pneumonia by veterinarians. Based on clinical experience, peer-reviewed studies, and laboratory data in experimental animal models, LLLT mitigates the cytokine storm at various levels and reduces inflammatory metabolites.	As the mortality of COVID-19 is closely related to respiratory syndrome and cytokine storm, in addition to the presence of lesions in the lungs caused by the use of a ventilator for longer than expected, LLLT is a resource that can be associated with the treatment and recovery COVID-19, still needing clinical trials to assess this approach objectively.
Sigman; Mokmeli; Vetrici, 2020 [34]	Case report	Human	This case report demonstrated the use of low-level laser therapy (LLLT) applied to a 32-year-old patient, morbidly obese with severe COVID-19. The patient received four sessions once a day using a laser scanner. Pulsed laser beams of 808 nm and 905 nm were applied to the posterior part of the chest for 28 min. Before treatment, oxygen saturation (SpO2) via pulse oximetry was 88–93% with 5–6 L of oxygen.	The patient was evaluated before and after LLLT and showed significant improvement. Increasing the SPO2 increased to 97–99% with 1–3 L of oxygen. The RALE score was reduced from 8 to 3, Brescia COVID from 4 to 0, and SMART-COP from 5 to 0. Interleukin-6 decreased from 45.89 to 11.7 pg/mL, ferritin from 359 to 175 ng/mL and CRP from 3.04 to 1.43 mg/dL. In addition, the patient noticed a considerable improvement in respiratory symptoms.	Due to the improvement in the respiratory indexes in a few days, radiological findings and inflammatory markers, the case report suggests that the adjunctive LLLT may be an ally to the conventional treatment of patients with severe COVID-19 and morbid obesity.
Sigman et al., 2020 [35]	Case report	Human	In this case report of a severe case of pneumonia caused by COVID-19, PBMT was used in in a 57-year-old man who received four sessions of PBMT once a day using a pulsed 808 nm and super laser scanner pulsed at 905 nm for 28 min. The patient was evaluated before and after treatment utilizing radiological assessment of lung edema (RALE), pulmonary severity indices, blood tests, oxygen requirements, and questionnaires.	After treatment, oxygen saturation increased from 93–94% to 97–100%, while the oxygen requirement decreased from 2–4 L/min to 1 L/min. The RALE score improved from 8 to 5. The Pneumonia Severity Index improved from Class V (142) to Class II (67). The additional pulmonary indices (Brescia-COVID and SMART-COP) decreased from 4 to 0. CRP normalized from 15.1 to 1.23. In addition, the patient reported significant improvement in the Community-Acquired Pneumonia assessment.	With PBMT, respiratory rates, oxygen requirement, and radiological findings improved significantly over the days, and there was no need for a ventilator, suggesting the use of PBMT as a complementary treatment for patients with pneumonia due to COVID-19, requiring further clinical trials to assess the effects.
Marchi et al., 2020 [36]	Randomized placebo-controlled trial research	Human	This study investigated whether PBMT-sMF is able to decrease the length of stay in the Intensive Care Unit (ICU) and to reduce the mortality rate of patients with severe COVID-19 who require invasive mechanical ventilation. Patients were randomly assigned to receive PBMT-sMF (6 sites on the lower chest—189 J in total and 2 sites in the neck area—63 J in total) or PBMT-sMF placebo daily for the entire ICU stay.	The 30 patients were submitted to randomization (15 receiving PBMT-sMF and 15 placebos). There was no statistical difference between the groups for the length of stay in the ICU. Regarding secondary studies, statistical differences were observed in favor of PBMT-sMF for diaphragm thickness, the fraction of inspired oxygen, partial pressure of oxygen/fraction of inspired oxygen, reactive protein C, lymphocyte count, and hemoglobin.	The study demonstrated that for patients with severe COVID-19 who require invasive mechanical ventilation, PBMT-sMF was not statistically different from placebo for the length of stay in the ICU, but improved diaphragm muscle function, ventilation and led to decreased levels of C-reactive protein (PCR) and hemoglobin count, in addition to increased lymphocyte count.
Moskvin; Askhadulin; Kochetkov, 2021 [37]	Review and experimental, in vivo research	Human	106 patients were treated at two health centers in Russia. A total of 22 had SARS pneumonia and were admitted for pulsed infrared rehabilitation; 14 patients had acute forms of COVID-19 and were treated with the LASMIK device, wavelength 904 nm, pulsed mode, externally and ILBI-525 (intravenous laser blood illumination) + LUVBI (ultraviolet laser blood illumination); 70 people have taken preventive non-invasive LLLT courses.	LLLT is effective in preventing the development of endothelial dysfunction. Clinically, there was good tolerability of the treatment and improvement in sputum discharge and general health. In the fifth procedure, the severity of general hypoxia decreased, and in the prevention procedures, there was good tolerance, and there were no cases of COVID-19.	LLLT is a treatment method that promotes lung tissue regeneration and mitigates the consequences of COVID-19. Thus, LLLT can be used for both prevention and treatment in patients with COVID-19.