Low level laser therapy as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce the use of ventilators in COVID-19

Abstract

S Mokmeli MD, M Vetrici MD. Low level laser therapy as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce the use of ventilators in COVID-19. Can J Respir Ther 2020;56:1-7. doi: 10.29390/cjrt-2019-015.

The global pandemic COVID-19 is a contagious disease and its mortality rates ranging from 1% to 5% are likely due to acute respiratory distress syndrome (ARDS), and cytokine storm. A significant proportion of patients who require intubation succumb to the disease, despite the availability of ventilators and the best treatment practices. Researchers worldwide are in search of anti-inflammatory medicines in the hope of finding a cure for COVID-19. Low-level laser therapy (LLLT) has strong, anti-inflammatory effects confirmed by meta-analyses, and it may be therapeutic to ARDS.

LLLT has been used for pain management, wound healing, and other health conditions by physicians, physiotherapists, and nurses worldwide for decades. In addition, it has been used in veterinary medicine for respiratory tract disease such as pneumonia. Laser light with low-power intensity is applied to the surface of the skin to produce local and systemic effects. Based on the clinical experience, peer-reviewed studies, and solid laboratory data in experimental animal models, LLLT attenuates cytokine storm at multiple levels and reduces the major inflammatory metabolites. LLLT is a safe, effective, low-cost modality without any side-effects that may be combined with conventional treatment of ARDS.
We summarize the effects of LLLT on pulmonary inflammation and we provide a protocol for augmenting medical treatment in COVID-19 patients. LLLT combined with conventional medical therapy has the potential to prevent the progression of COVID-19, minimize the length of time needed on a ventilator, enhance the healing process, and shorten recovery time.

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Published online at https://www.cjrt.ca on 21 July 2020
RESEARCH ARTICLE
Low level laser therapy as a modality to attenuate cytokine
storm at multiple levels, enhance recovery, and reduce
the use of ventilators in COVID-19
Soheila Mokmeli MD Anesthesiologist1, Mariana Vetrici MD, PhD2
S Mokmeli MD, M Vetrici. Low level laser therapy as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce
the use of ventilators in COVID-19. Can J Respir Ther 2020;56:1–7. doi: 10.29390/cjrt-2019-015.
The global pandemic COVID-19 is a contagious disease and its mortality rates ranging from 1% to 5% are likely due to acute respiratory distress syndrome
(ARDS), and cytokine storm. A significant proportion of patients who require intubation succumb to the disease, despite the availability of ventilators and
the best treatment practices. Researchers worldwide are in search of anti-inflammatory medicines in the hope of finding a cure for COVID-19. Low-level
laser therapy (LLLT) has strong, anti-inflammatory effects confirmed by meta-analyses, and it may be therapeutic to ARDS. LLLT has been used for pain
management, wound healing, and other health conditions by physicians, physiotherapists, and nurses worldwide for decades. In addition, it has been used
in veterinary medicine for respiratory tract disease such as pneumonia. Laser light with low-power intensity is applied to the surface of the skin to produce
local and systemic effects. Based on the clinical experience, peer-reviewed studies, and solid laboratory data in experimental animal models, LLLT attenu-
ates cytokine storm at multiple levels and reduces the major inflammatory metabolites. LLLT is a safe, effective, low-cost modality without any side-effects
that may be combined with conventional treatment of ARDS. We summarize the effects of LLLT on pulmonary inflammation and we provide a protocol
for augmenting medical treatment in COVID-19 patients. LLLT combined with conventional medical therapy has the potential to prevent the progression
of COVID-19, minimize the length of time needed on a ventilator, enhance the healing process, and shorten recovery time.
Key Words: COVID-19; ARDS; cytokine storm; low level laser therapy; anti-inflammator y; ventilator; photobiomodulation
INTRODUCTION
What is low level laser therapy?
Low level laser therapy (LLLT) is also known as cold laser therapy or photo-
biomodulation therapy. LLLT utilizes visible light and infrared laser beams
in the range of 450–1000 nm. Single wavelength or monochromatic light is
emitted from a low-intensity laser diode (<500 mW). The light source is
placed in contact with the skin, allowing the photon energy to penetrate
tissue, where it interacts with various intracellular biomolecules to restore
normal cell function and enhance the body’s healing processes [1]. This
contrasts with the thermal effects produced by the high-power lasers that are
used in cosmetic and surgical procedures to destroy tissue [1], as mentioned
in the PubMed Medical Subject Heading (MeSH) subheading for LLLT.
LLLT effects are not due to heat but rather to a photochemical reaction
that occurs when a photoacceptor molecule within the cell absorbs a pho-
ton of light, becomes activated, and changes the cell’s membrane permea-
bility and metabolism. Presently, cytochrome c oxidase, opsins and their
associated calcium channels, and water molecules have been identified as
the main mediators of the photochemical mechanisms [2]. This leads to
increased mRNA synthesis and cell proliferation. LLLT produces reactive
oxygen species (ROS) in normal cells, but ROS levels are lowered when it
is used in oxidatively stressed cells, like in animal models of disease. LLLT
up-regulates antioxidant defenses and decreases oxidative stress [2].
Low-level lasers are a safe, noninvasive technology approved by both
the US Food and Drug Administration and Health Canada for several
chronic and degenerative conditions, temporary pain relief, cellulite
treatment, body contouring, lymphedema reduction, hair growth, and
chronic musculoskeletal injuries. LLLT increases microcirculation, lym-
phatic drainage, and cellular metabolism, thereby relieving many acute
and chronic conditions.
The MeSH database in PubMed contains more than 7000 articles on
LLLT. The effects of LLLT have been confirmed through several meta-
analysis studies and include anti-inflammatory [3] and analgesic effects [4],
tissue healing [5], treating tendinopathy [6], and improving lymphedema
[7]. Recent lab and animal studies suggest LLLT is ready for clinical trials
over myocardial infarction [5]. In 2010, a meta-analysis concluded that there
was strong evidence of an anti-inflammatory effect of LLLT [3].
To date, published reports indicate that LLLT up-regulates antioxi-
dant defenses and decreases ROS in oxidatively stressed cells and animal
models of disease. The anti-inflammatory effect of LLLT directly
addresses the main pathology of disorders such as musculoskeletal,
lungs, wounds, brain, trauma, etc. LLLT reduces NF-kB, a protein com-
plex that controls transcription of DNA, in pathological conditions.
Reports have shown reductions in reactive nitrogen species and prosta-
glandins in various animal models [2].
LLLT has diverse effects [8]:
• reduces pain related to inflammation via dose-dependent reduc-
tion of prostaglandin E2, prostaglandin-endoperoxide synthase-2,
IL-1, IL-6, TNFa, as well as the cellular influx of neutrophils, oxi-
dative stress, edema, and bleeding;
1Canadian Optic and Laser Center (Training Institute), Victoria, BC, Canada
2Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
Correspondence: Soheila Mokmeli, Canadian Optic and Laser Center (Training Institute), 744A Lindsay Street, Victoria, BC V8Z 3E1, Canada.
Tel.: +1 (250) 480-7868, E-mail: dr.mokmeli@yahoo.com Mariana A. Vetrici, Department of Biological Sciences, University of Lethbridge, 4401 University
Drive, Lethbridge, AB T1K 3M4, Canada, Tel.: +1 (865) 888-3095, E-mail: marianavetrici@gmail.com

Soheila Mokmeli and Mariana Vetrici
2 Can J Respir Ther Vol 56
• decreases edema and swelling by increasing lymphatic drainage;
• increases collagen and protein production, and cell proliferation;
• accelerates wound healing and scar formation;
• improves quality and tensile strength of tissue;
• stimulates nerve function and regeneration;
• accelerates bone regeneration and remineralization;
• reduces the pain threshold and enhances endorphins;
• washes inflammatory debris away from the injured site; and
• augments blood flow.
LLLT has been used in respiratory tract diseases since 1978. Empirical
practice on over 1000 patients produced data pertaining to chronic pneu-
monia, acute pneumonia, asthma, and chronic bronchitis in children,
adults, and elderly. Common findings include reduced chest pain and
heaviness; normalization of respiratory function; improved blood, immu-
nological, and radiological parameters; and shortened recovery times. In
community-acquired pneumonia, intravenous LLLT of blood added to
conventional treatment significantly promoted the bactericidal activity of
neutrophils. In asthma, the addition of LLLT was more effective than
medical treatment alone and it shortened the duration of treatment and
recovered bronchial sensitivity to sympathomimetics [9–11]. In newborns
with pneumonia, LLLT combined with conventional medical regimens
optimized the treatment infectious and inflammatory diseases, reduced
the incidence of complications, and shortened recovery periods [12].
LLLT is a well-known treatment modality in veterinary medicine.
Upper and lower respiratory conditions in dogs and cats are common, and
viral and bacterial infections are often highly contagious. Regardless of
etiology, inflammation is the major pathology of these conditions. The
addition of LLLT to conventional treatment alleviates symptoms and stim-
ulates the healing process in tissues. General guidelines for the use of laser
therapy in animals and protocols for specific conditions are published [13].
The pathogenesis of COVID-19 in respiratory tract
Coronaviruses are a large group of viruses that affect animals. In humans,
they produce diseases such as the common cold, severe acute respiratory
syndrome (SARS) and Middle East respiratory syndrome. The disease
caused by the novel coronavirus, SARS-CoV-2, has been named COVID-
19 and the clinical manifestations range from asymptomatic to severe
acute respiratory distress syndrome (ARDS) to death [14].
Respiratory viruses infect either the upper or lower airways. Typical
upper-respiratory infections are milder, more contagious, and spread eas-
ily, whereas lower-respiratory infections spread much less frequently but
are more severe and dangerous. SARS-CoV-2 appears to infect both
upper and lower airways. It spreads while still limited to the upper air-
ways, before traveling into the deeper respiratory tract and leading to
severe symptoms [15].
SARS-CoV-2 attaches to a protein called angiotensin converting
enzyme (ACE2), on the surface of cells in the respiratory tract. As SARS-
CoV-2 attacks the cells, dead cells flow down and block the airways with
debris while the virus moves deeper into the lungs. Breathing becomes
difficult because the lungs become clogged with dead cells and fluid.
The immune system attacks the virus causing inflammation and fever. In
severe cases, the immune system goes wild, causing more damage to the
lungs than the actual virus. Blood vessels dilate to increase blood flow
and become more permeable to maximize transport of chemical and cel-
lular mediators the infection site. Inevitably, the lungs get filled with
fluid. This exaggerated immune response is called cytokine storm and it
leads to ARDS, fever, multiorgan failure, and death [15, 16].
During cytokine storm, the immune system attacks indiscriminately
without clearing the specific targets. Cytokine storm also affects other
organs, especially if people already have chronic diseases [15]. The sever-
ity of cytokine storm determines who is hospitalized and who will be
treated in the intensive care unit (ICU). The classification of COVID-19
is summarized in Table 1 [17].
The morbidity and mortality of COVID-19 are due to excessive
inflammatory cytokine production and immune hyperactivity. Alveolar
macrophage activation and cytokine storm are the main pathogenesis of
severe COVID-19. The pathological features include exudation and
hemorrhage, epithelial injuries, infiltration of macrophages into the
lungs, and fibrosis of lung tissue. The mucous plug with fibrinous exu-
date in the alveoli and the activation of alveolar macrophage are charac-
teristic abnormalities [18, 19]. Chemical and genetic studies have shown
that the pulmonary endothelium is a key component of the cytokine
storm. Therefore, modulation of the involved cellular signaling pathways
may have therapeutic effects [20, 21].
COVID-19 begins when SARS-CoV-2 uses ACE2 as the entry recep-
tor for infection [22]. This induces ACE2 downregulation and shedding.
Loss of ACE2 from the endothelium causes dysfunction of the renin-an-
giotensin system, and it enhances inflammation and vascular permeabil-
ity. Shedding of ACE2 from the endothelium releases enzymatically
active soluble ACE2 (sACE2), which is tightly linked to tumor necrosis
factor alpha (TNF-α) production in cell culture [23].
Multiple signaling pathways are activated during an immune
response and cytokine storm. The P2X purinoceptor 7 (P2X7r) is major
TABLE 1
The staging and classication of COVID-19 [17]
Class Symptoms Imaging Respiratory criteria
Mild infection Mild Negative signs of pneumonia Normal
Moderate infection Fever and upper respiratory
tract symptoms
Positive signs of pneumonia Normal
Severe infection Fever, upper and lower
respiratory tract symptoms
>50% lesion progression
within 24–48 hours
Respiratory rate ≥ 30 /min
O2 saturation ≤ 93% at rest
Arterial partial pressure of O2 (PaO2)/oxygen concentration (FiO2)
≤ 300 mm Hg
Critical infection Respiratory failure requiring
mechanical ventilator
and (or)
presence of shock
and (or)
other organ failure that requires
monitoring and (or) treatment in
the ICU
> 50% lesion progression
within 24–48 hours
Early stage:
• Oxygenation index 100.1–149.9 mmHg.
• Respiratory system compliance (RSC) ≥ 30 ml/cmH2O.
• No organ failure other than the lungs.
Middle stage:
• 60 mmHg < O2 index ≤ l00 mmHg.
• 30 mL/cmH2O > RSC ≥ 15 mL/cmH2O.
• Maybe complicated by mild or moderate dysfunction of other organs.
Late stage:
• O2 index ≤ 60 mmHg.
• RSC < 15 mL/cmH2O.
• Diffuse consolidation of both lungs that requires the use of extracorpo-
real membrane oxygenation or failure of other vital organs.
Note: A conrmed case is based on the epidemiological history (including cluster transmission), clinical symptoms (fever and respiratory symptoms), lung imaging,
and results of SARS-CoV-2 nucleic acid detection and serum-specic antibodies [17].

Low level laser therapy for COVID-19
Can J Respir Ther Vol 56 3
factor involved in activation of the cytokine storm and lung pathology in
response to viruses [24, 25], infection, inflammation, hypoxia, or trauma
[26]. P2X7r is an adenosine triphosphate (ATP) gated, nonselective cat-
ion channel, allowing Ca2+ and Na+ influx and K+ efflux. Extracellular
ATP plays a central role in apoptotic cell death [27], the induction of
inflammation [28], and mitochondrial failure in monocytes [29]. P2X7r
mediates ATP-induced cell death in different cells and it promotes
assembly and release of proinflammatory interleukins (IL -1β and IL-18)
from immune cells after exposure to lipopolysaccharide and ATP [27].
P2X7r is constitutively expressed in many cells, including respiratory epi-
thelial cells and most immune cells like neutrophils, monocytes, macro-
phages, dendritic, natural killer, B and T lymphocytes [27].
Studies stratified COVID-19 patients as: (i) severe symptoms and
ICU admission and (ii) mild and moderate symptoms requiring hospital-
ization but not ICU [17, 19]. The severe patients have significantly
higher levels of plasma pro-inflammatory factors (IL-2, IL-7, IL -10,
GSCF, IP-10, MCP-1, MIP1A, TNF-α) [19] and (IL-2, IL-6, IL-10, TNF-α)
[18] than non-ICU patients, and they were likely in cytokine storm [17,
19]. These findings justify the use of IL-6 receptor antagonists [18, 19];
however, a therapy to reduce inflammation at multiple levels, such as
LLLT, could be more successful in controlling the unbalanced immune
response (Figure 1).
The effects of LLLT on pulmonary inflammation
LLLT is effective against cytokine storm and ARDS while promoting
healing and tissue regeneration. Experimental and animal models of pul-
monary disease and infection have revealed multiple cellular and molec-
ular effects, which are both local and systemic. LLLT reduces
inflammation without impairing lung function in acute lung injuries
and is a promising therapeutic approach for lung inflammatory diseases
such as Chronic obstructive pulmonary disease [26].
In murine models of acute inflammation of the airways and lungs,
transcutaneous LLLT delivered over the trachea decreases pulmonary
microvascular leakage [30, 31], IL-1b levels [26, 30], IL -6 [26, 32],
MIP-2 mRNA expression [30], and intracellular ROS production [24].
LLLT produces anti-inflammator y effects on tracheal hyperactivity, and
reduces neutrophil influx [26, 30, 32–34] by inhibiting COX-2-derived
metabolites [33]. In ARDS, LLLT elevates cyclic adenosine monophos-
phate [32, 34], a signaling molecule that stimulates IL-10 and G-CSF expres-
sion and blocks TNF-a and MIP-1. LLLT also reduces TNF-a levels in
bronchoalveolar lavage fluid and alveolar macrophages [26, 31–34]. In hem-
orrhagic lesions of the lungs, LLLT significantly reduces the hemorrhagic
index and myeloperoxidase activity, to levels comparable to Celecoxib [35].
LLLT contributes to the resolution of inflammation by upregulating
IL-10 and downregulating P2X7r. LLLT changes the profile of inflamma-
tory cytokines and elevates IL-10 [26, 31, 36], known as human cytokine
synthesis inhibitory factor, in the lung and abolishes lung inflammation
via a reduction of inflammatory cytokines and mast cell degranulation
[31]. LLLT decreases collagen deposition as well as the expression of the
P2X7r [26].
LLLT contributes to healing by promoting apoptosis of inflamma-
tory cells while suppressing apoptotic pathways in lung tissue. In a model
of acute lung injury, LLLT reduced DNA fragmentation and apoptotic
pathways via increased B-cell-lymphoma-2 (Bcl-2), the key regulator of the
intrinsic or mitochondrial pathway for apoptosis, in alveolar epithelial
cells while promoting DNA fragmentation in inflammatory cells [37]. In
pulmonary idiopathic fibrosis, LLLT inhibits pro-inflammatory cyto-
kines and increases expression of proliferating cell nuclear antigen [38],
attenuates airway remodeling by balancing pro- and anti-inflammatory
cytokines in lung tissue, and inhibiting fibroblast secretion of the
pro-fibrotic cytokines [36].
LLLT provides synergy in combination with medical treatment. It has
a synergic anti-inflammatory action over alveolar macrophages pretreated
with N-acetyl cysteine, an effective oral medicine for coughs and some lung
conditions [39]. The synergic effects of LLLT combined with conventional
treatments were reported on over 1000 patients in Russian studies [9–11].
FIGURE 1
The effects of SARS-CoV-2 on alveolar cell and cytokine storm.

Soheila Mokmeli and Mariana Vetrici
4 Can J Respir Ther Vol 56
Extended time on ventilators causes lung injury but LLLT minimizes
this side effect. In experimental models of ventilator-induced lung injury
(VILI), LLLT following VILI resulted in lower injury scores, decreased
total cell count and neutrophil count in bronchoalveolar lavage, and
reduced alveolar neutrophil infiltration. LLLT in an experimental model
of VILI in rats demonstrated the anti-inflammatory effect via decreased
lung injury scores and lower counts of neutrophils in alveolar, intersti-
tial, and bronchial lavage [39] (Figure 2).
Evidence from the literature supports the use of LLLT for the treat-
ment of COVID-19.
• It has significant anti-inf lammatory effects confirmed by meta-
analyses. Eleven cell studies, 27 animal studies, and another six
animal studies for drug comparisons and LLLT interactions veri-
fied that there is strong evidence of an anti-inflammatory effect of
LLLT. The scale of the anti-inf lammatory effect is not significantly
different than non-steroidal anti-inflammatory drugs, but it is
slightly less than glucocorticoid steroids [3].
• It has diverse applications and effects confirmed through several
meta-analysis studies include analgesia [4], tissue healing [5], treat-
ing tendinopathy [6], and improved lymphedema [7].
• LLLT is approved by the US FDA and Health Canada for several
chronic and degenerative conditions, temporary pain relief, cellu-
lite treatment, body contouring, lymphedema reduction, and hair
growth. It has been used in veterinary medicine for upper and
lower respiratory conditions in dogs and cats [13].
• It has been used for human respiratory tract disease. Empirical use
on over 1000 patients produced data pertaining to chronic pneu-
monia, acute pneumonia, asthma, and chronic bronchitis in chil-
dren, adults, and the elderly [9–12]. Light therapy and LLLT has
been mentioned as a potential treatment for pandemic coronavirus
infections [40].
• The anti-inf lammatory effect of LLLT in lung inflammation is con-
firmed in at least 14 experimental animal studies. LLLT attenuates
cytokine storm at multiple levels and reduces the major inflamma-
tory metabolites such as IL-6 and TNF-α. IL-6 antagonists are
being investigated for treating COVID-19 but LLLT reduces the
production of IL-6, as well as other chemokines and metabolites
[26–39, 41].
• There are US FDA and Health Canada approved laser machines
for pain management, lymphedema after breast cancer surgery,
and cellulite treatments that can be used and set to treat lung
inflammation.
• LLLT is an affordable modality compared with other treatments
and medicines like IL-6 antagonists. LLLT is a safe, effective, low-
cost modality without any reported side-effects compared with
other approaches. A laser machine costs Can$35,000.00–
200,000.00, and each machine can fully treat 20,000 patients for
COVID-19. In comparison, an IL-6 antagonist costs US$1000.00
per injection, and each patient would need 3–6 injections for com-
plete COVID-19 treatment. Treating 20,000 patients would cost
US$ 60,000,000.00–US$ 120,000,000.00.
Based on this information, LLLT will accelerate recovery from COVID-
19 and will get patients off ventilator support and out of the ICU more
rapidly. This could significantly decompress our severely overburdened
health care systems.
Therapeutic technique and dosage of LLLT
Laser dose is the amount of energy delivered per second per cm2. The effect
of laser therapy is related to the amount of laser energy per cm2. The Arndt-
Schultz Law is considered the standard to describe the dose dependent
effects of LLLT [42]. The minimum therapeutic dose for a bio-stimulatory
effect for red and infrared laser is 0.01 J/cm2 while for ultraviolet, blue,
green laser it is 0.001 J/cm2. LLLT has a noticeable biphasic dose response.
The effective stimulation dose is 1 J/cm2 on the target tissue. Doses greater
than 10 J/cm2 produces inhibitory effects. The inhibitory effects are used
in conditions requiring inhibition and suppression [2].
FIGURE 2
The effects of SARS-CoV-2 versus LLLT on cytokine storm and lung tissue.

Low level laser therapy for COVID-19
Can J Respir Ther Vol 56 5
Therapeutic protocol: early phase of COVID-19: (Figure 3, Table 2)
Laser parameters:
• Laser type: infrared laser (780–900 nm), or red laser (630–660 nm)
• Average power: 50–100 mW
• Dose: 4–6 J/cm2
• Area: 10 cm2
• Time: 1–2 minutes/cm2
• Sessions: 3–8 once-daily sessions
Laser probe positions:
• Intranasal: 2 minutes, noncontact technique
• Over right and left tonsils: transcutaneous (place laser over the
skin)
• Over the trachea: transcutaneous
• Over the veins in the cubital areas: transcutaneous blood laser
therapy, 10–15 minutes
Therapeutic protocol: medium–severe phase of COVID-19:
(Figure 3, Table 3)
Laser parameters:
• Laser type: infrared laser (780–900 nm) or red laser (630–660 nm)
• Average power: 50–100 mW
• Dose: 6–10 J/cm2
• Area: 10 cm2
• Time: 2–3 minutes/cm2
• Sessions: 3–10 once-daily sessions
Laser Probe Positions:
• Over the lungs: bilaterally over apical, middle, and lower lobes and
front and back of thorax, transcutaneous over the intercostal spaces
• Over the trachea: transcutaneous
• Over the bronchus: upper mediastinal area, transcutaneous
• Over right and left tonsils: transcutaneous
• Over the veins in the cubital areas: transcutaneous blood laser
therapy; 10–15 minutes
Contraindications and side effects of LLLT [42]
Although LLLT is safe and noninvasive and there are no reports of muta-
genicity, genotoxicity, or carcinogenicity of LLLT after 60 years of its use.
However, there are some contraindications:
• work over the site of tumors and cancer;
• benign tumors with possibility of converting to malignant tumors;
FIGURE 3
LLLT for COVID-19.
TABLE 2
Therapeutic protocol: Early phase of COVID-19
Laser system parameters
Wavelengths Infrared laser (780–900 nm), or red
laser (630–660 nm)
Average power 50–100 mW
Dose 4–6 J/cm2
Area 10 cm2
Sessions 3–8 once-daily sessions
Laser probe positions
Intranasal:
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Noncontact technique
Over right and left tonsils
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Transcutaneous
(place laser over the skin)
Over the trachea
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Transcutaneous
Over the veins in the cubital areas
8 minute/cm2 (100 mW)
15 minutes/cm2 (50 mW)
Transcutaneous blood laser therapy

Soheila Mokmeli and Mariana Vetrici
6 Can J Respir Ther Vol 56
• the first 3 months of pregnancy (in the second and third trimes-
ters, avoid work on abdominal and spine area); and
• light sensitivity conditions.
Precautions [42]
• epiphyseal line in children;
• glands: avoid ovaries, testes;
• in patients with severe end organ damage: heart, kidney, liver, and
lung;
• epilepsy: the possibility of ner ve discharge is increased in LLLT,
especially with low-frequency protocols, 5–10 HZ.
Side effects of LLLT
Optical side effects
Because of the high intensity of lasers and the absorption of its wave-
lengths by different parts of ocular system, there is a possibility of dam-
age to the eyes. It is important to use protective glasses that can absorb
the specific wavelength. Protective glasses for each wavelength are differ-
ent; therefore, choose the protective goggles specified for each wave-
length. Both therapists and clients should wear protective goggles [42].
Early sense of healing
The analgesic effect of laser manifests earlier than its healing effect, and
the patients feel better because of this, but the actual tissue damage has
not yet healed. Patients feel relaxed and more energetic because the pain
is gone. However, they must allow enough time for recovery [42].
Fatigue and tiredness
Fatigue is the most common symptom following LLLT. This is due to
hormonal and metabolite changes after laser therapy that increase
expression natural pain killers like endorphins and enkephalins. These
metabolites induce relaxation and sleepiness [42].
Low blood pressure and dizziness
Very rarely, when the treated area is close to large blood vessels, a patient
may experience a temporary drop in the blood pressure and orthostasis.
This is due to vasodilatation and increased circulation to the limbs. To
avoid dizziness, it is recommended that patients drink fluids before
LLLT, and then wait for a few minutes before getting up from the supine
position [42].
CONCLUSION
COVID-19 is potentially lethal because of cytokine storm and ARDS.
Although most patients who contract COVID-19 may recover at home,
a significant proportion require hospitalization and (or) ICU treat-
ment. Many of the patients that are placed on ventilators succumb to
the disease despite the best treatment practices. Often, patients are
maintained on ventilators for longer than expected, and this may con-
tribute to ventilator induced lung injury while depleting the patient’s
convalescent resources. Modulation of inflammatory factors and a
boost to healing are necessary to help patients come off the ventilators.
LLLT is a safe and noninvasive modality that has been used for decades
in pain management, wound healing, and health conditions including
diseases of the respiratory tract. LLLT was combined successfully with
standard medical care to optimize response to treatments, reduce
inflammation, promote healing, and accelerate recovery times.
Scientific evidence shows that LLLT attenuates the inflammator y cyto-
kines and chemokines in cytokine storm at multiple levels. In addition,
LLLT promotes apoptosis of inflammatory cells and protects alveolar
cells from damage. These findings suggest that LLLT is a feasible
modality in the treatment of ARDS. LLLT can be added to the conven-
tional treatment in COVID-19 at different stages of the disease.
Because of its anti-inflammatory effect, and ability to shorten recovery
times, LLLT can reduce the need of ventilators in the healing process.
Clinical trials are necessary to objectively evaluate the effect of LLLT
on COVID-19 treatment and recovery.
Contributors
Soheila Mokmeli and Mariana Vetrici contributed to the conception
and design of the work.
Competing interests
All authors have completed the ICMJE uniform disclosure form at www.
icmje.org/coi_disclosure.pdf and declare: no financial relationships
with any organizations that might have an interest in the submitted work
in the previous 3 years; no other relationships or activities that could
appear to have influenced the submitted work.
Ethical approval
Informed consent was obtained from all participants.
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TABLE 3
Therapeutic protocol: medium–severe phase of COVID-19
Laser system parameters
Wavelengths Infrared laser (780–900 nm), or red laser
(630–660 nm)
Average power 50–100 mW
Dose 6–10 J/cm2
Area 10 cm2
Sessions 3–10 once-daily sessions
Laser probes positions
Intranasal:
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Noncontact technique
Over right and left tonsils
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Transcutaneous
(place laser over the skin)
Over the trachea
1 minute/cm2 (100 mW)
2 minutes/cm2 (50 mW)
Transcutaneous
Over the veins in the cubital
areas
8 minute/cm2 (100 mW)
15 minutes/cm2 (50 mW)
Transcutaneous blood laser therapy
Over the lungs
1:30–2 minute/cm2 (100 mW)
2–3 minutes/cm2 (50 mW)
Bilaterally over apical, middle, and lower
lobes, front and back of thorax; transcuta-
neous over the intercostal spaces
Over the bronchus
1:30–2 minute/cm2 (100 mW)
2–3 minutes/cm2 (50 mW)
Upper mediastinal area: transcutaneous

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