Photodynamic Therapy for the Treatment of COVID-19
Photodynamic Therapy for the Treatment of COVID-19
Until now there is no vaccine or reliable treatment for the COVID-19 pandemic. The
 fundamental mechanisms of non-invasive low-level laser in photobiomodulation (PBM) and
 photodynamic therapy is to stimulate the mitochondrial respiratory chain where a transient
 release of non-cytotoxic levels of reactive oxygen species (ROS) will lead to positive
 modulation of the immune response. As previous studies mentioned that the most important
 strategy for COVID-19 management is oxygenation and faster rehabilitation of the damaged
 tissue, antiviral effects, and, ﬁnally, reduction or controlling the cytokine storm by
 reducing inﬂammatory agents. PBM may be used as adjuvant therapy or even an alternative
 therapy in all these mechanisms without side effects and drug interactions.

 Objectives The objective of this clinical trial is to use the photobiomodulation therapy
 (PBMT), and photodynamic therapy as adjuvant therapy or even an alternative therapy for
 Covide-19.

 Patients and methods A randomized controlled study will be conducted on 60 patients of
 positive COVID 19. The patients will be divided into 3 equal groups. Group, I will receive a
 low-level laser (diode laser 980nm) from laser watch for 30 minutes, 20 J for 3 to 5 days,
 and laser acupuncture. Group 2 will be treated with photodynamic therapy by injecting the
 methylene blue as a photosensitizer and irradiated with laser watch (diode laser 670 nm).
 Group 3 will serve as a control. Evaluation methods will include laboratory investigations
 and CT chest.
Treatment protocol:

 This clinical study was conducted following the approval of the research ethics committee for
 experimental and clinical studies at the National Institute of Laser Enhanced Sciences, Cairo
 University, Egypt (approval number CU-NILES/16/20 May 2020) with the principles outlined in
 the Declaration of Helsinki for human subject experimentation being followed. Informed
 consent will be obtained from the patients, and the privacy rights will be continuously
 observed.

 This study will be conducted on 60 patients with COVID 19 of all ages and both sex.

 Patients will be divided into 3 groups:

 Group 1: photobiomodulation This group included the use of laser watch and laser acupuncture

 Laser watch Patients will be subjected to low level laser (diode laser 980nm) for 30 minutes,
 the recommended dose based on previous study is 20 J for 3 to 7 days.

 The laser device:

 Laser watched applied at the wrist on the radial artery.

 Laser acupuncture Patients will receive laser acupuncture using pulsed infra- red laser,
 wavelength 880 / 905/980 nm, spot size diameter of 5 mm frequency 2500 Hz, average power 15
 W, energy of 225 mJ applied for 2 min per point and pulse width of 100 ns and area = 0.2 cm2.
 Patients will receive one session daily for 7 days.

 Laser acupuncture was applied at the following points (World Health Organization 2008). The
 points where the laser acupuncture will be applied are demonstrated in the following figures:

 -  For cough and chest tightness, wheezes and congestion: LU1, 2, 5, 7, 9, 14 (fig.1) For
 improving immunity and blood circulation, also for dyspnea and GIT manifestation also,
 breaks up blood stagnation in the chest: ST36

 -  Affects the throat, chest, lungs: CV12, CV4 Sore throat, coughing, & asthma: KI3 Fig

 -  Laser acupuncture device could be applied simultaneously on all points same time by
 special multi-channel device (fig3)

 Group 2 (photodynamic therapy) Methylene blue injection USP 1% will be used as a
 photosensitizer in PDT.

 -  0.1 to 0.2 mL of 1% solution per kilogram of body weight Methylene Blue (methylene blue
 injection) will be injected intravenously very slowly over a period of several minutes
 to prevent local high concentration of the compound from producing methemoglobin (low
 concentrations will convert methemoglobin to hemoglobin and will be activated by light).

 -  After one hour apply Light dose: 100 - 200 J/cm2 50-100 mW/cm2. (50 mW/cm2 increased the
 phototoxic response as well as fractionated light application).

 -  Session will be done twice per week

 The laser device:

 Laser watched applied at the wrist on the radial artery. Group 3: positive control This group
 will include patients who are subjected to conventional treatment Evaluation and assessment
 All patients will be subjected to thorough examination with complete personal and clinical
 history and will do the following before and after treatment: PCR, CBC, CRP, ESR, D dimers,
 liver enzymes, and Ferritin, CT chest

 Endpoint Treatment will be stopped if no improvement occurred after one week

 Statistical analysis

 All statistical calculations were done using computer programs SPSS (Statistical Package for
 the Social Science; SPSS Inc., Chicago, IL) v.16 for Microsoft Windows. Continuous variables
 were tested for normality by the Shapiro-Wilk normality test. Values are presented as mean ±
 standard deviation, or in the case of non-normally distributed data as median and
 inter-quartile range. For comparison between paired parameters (before and after treatment),
 paired t-test or the Wilcoxon matched-pairs signed-rank test were used according to data
 normality. For comparison between independent groups, the chi-squared test was used to
 compare percentages between different groups of patients. Normally distributed data were
 analyzed using independent samples t-test. Non-normally distributed data were analyzed using
 the Mann-Whitney U-test. p values <.05 were considered statistically significant.
Inclusion Criteria:

 -  Hospitalized patients with Positive COVID 19 test suffering from Fever, cough,
 shortness of breath, chills, muscle pain, the new loss of taste or smell, vomiting or
 diarrhea, and/or sore throat

 Exclusion Criteria:

 -  Patients in critical cases who admitted to the ICU, bacterial pneumonia, and
 respiratory distress grade III, IV, and patients on a mechanical ventilator.