SARS-CoV-2 is the coronavirus responsible for developing the disease known as COVID-19.Once the acute phase of the disease has passed, about 40% of the people who dischargedcontinue to have symptoms, and of these, between 50 and 70% present them up to threemonths later. These persistent symptoms include physical aspects such as fatigue anddyspnea, but also cardiac such as palpitations, cognitive such as mental confusion, andpsycho-emotional such as depression, anxiety, and stress. SARS-CoV-2 infection isassociated with a hyperinflammatory state, including excessive inflammatory cellinfiltration, inflammasomes activation. In this context, omega-3 metabolites (SpecialPro-resolving Mediators-SPMs) restore the balance in nutritional and molecular levels ofeicosanoids. A more direct and targeted way to increase SPMs levels is Omega3 EssentialNutrition with natural SPMs taken by mouth. Today, there are dietary supplementscontaining SPMs (LIPINOVA®), made from fish oil through a fractionation process.LIPINOVA® is a nutritional supplement patented by Solutex GC S.L., obtained throughseveral fractionation stages (extraction, purification, separation, concentration) fromrich-in-omega-3 fish oil (without additives). Each capsule contains 498 mg of fish oiland 2 mg of tocopherols. This represents a variable quantity from 50 to 150 mg of EPA(20%), a variable quantity from 100 to 225 mg of DHA (30%), as well as the followingquantities of EPA and DHA active metabolites, obtained from a pool of natural lipidmediators contained in omega-3 oil: 40-200 mcg of 17-HDHA, 25-200 mcg of 18-HEPE and20-100 mcg of 14-HDHA.In addition to this, the appearance of this new health condition, post-COVID condition,has once again led physiotherapists to update themselves in search of the best evidenceto guide the examination and necessary rehabilitation interventions in this type ofpatient. Studies have shown how physiotherapy sessions that include a multimodal programcould be the most indicated for this type of patients. Patients with this conditionpresent an increase in fatigue, dyspnea and a decrease in their functional capacity and,therefore, a decrease in their quality of life, due to various pathogenic mechanisms thatinclude chronic hyperinflammation.These patients could obtain greater health improvements in terms of their quality of lifeif a therapeutical exercise and education program based on tele-rehabilitation isimplemented together with a natural nutritional supplement that generates a systemicanti-inflammatory effect through SPMs (omega- 3).
Patients who have contracted COVID-19 usually show various symptoms during the infection:
Fever, cough, generalized pain, gastrointestinal disturbances, dyspnea, and fatigue. The
latter two symptoms occur in about half of patients worldwide, although they are even
more common in Europe. In addition to these respiratory symptoms, the disease can also
have effects at the muscular, neurological, and cardiovascular levels.
After the acute phase of the disease, approximately 40% of discharged patients still have
symptoms, and of these, 50% to 70% have symptoms up to three months later. These
persistent symptoms include physical aspects such as fatigue and shortness of breath, but
also cardiac symptoms such as palpitations, cognitive symptoms such as mental confusion,
and psychoemotional symptoms such as depression, anxiety, and stress.
However, it is also observed how this clinic can be maintained beyond three months. It is
known that there is a group of patients, about 5-10%, who have persistent symptoms over a
period of up to 2 years, and new symptoms may even appear, leading to persistent COVID.
Although the terminology for designating patients with this persistent clinical condition
is changing, on October 6, 2021, the WHO published a consensus document defining the
post-COVID condition (CPCOVID).
The possible mechanisms contributing to the overall pathophysiology of CPCOVID are still
unclear, and numerous factors have been proposed to date. A key element may be the
presence of a state of chronic hyperinflammation. In the lung context, the virus
activates innate immunity, leading to a cascade of inflammatory cytokines, including
interleukin-6 (IL -6), IL -1, tumor necrosis factor-alpha, and reactive oxygen species.
Some studies have attempted to demonstrate the presence of T cells and NK lymphocytes in
these patients, making it appear that COVID is characterized by alterations in TCD4+
cells and TCD8+ cells.
Other proposed mechanisms include autoimmune mechanisms through the presence of
autoantibodies that act against modulatory proteins that alter immune function. Also, the
hypercoagulable state (thromboinflammatory state) associated with SARS-CoV-2 infection is
responsible for the disproportionately high rates (20-30%) of thrombotic complications
observed in patients with COVID-19 and autonomic nervous system involvement leading to
autonomic dysfunction.
Therefore, controlling systemic inflammation and eliminating it in general is as
important as eradicating the virus itself. In particular, omega-3 fatty acids (EPA and
DHA) are substrates that modulate the immune system response by promoting the resolution
of inflammation by producing pro-resolving mediators that actively modulate and resolve
the immune system response. Thus, omega-6 (ARA) and omega-3 fatty acids (EPA and DHA) are
structural lipids, but the biological effects are carried out by their naturally produced
metabolites (SPMs). In cases where the acute response of the immune system is chronic,
deficiency of SPMs in the affected tissues has been observed (e.g., in metabolic diseases
{obesity, metabolic syndrome, diabetes type II, fatty liver}, dry eye, atherosclerosis,
autoimmune diseases, etc.). These effects on the metabolic pathways of SPM production may
reduce resolution and thus contribute to the chronicity of the inflammatory response.
Recently, severe COVID-19 was shown to be associated with an altered profile of SPMs
compared with healthy individuals. SPMs may have a new role in the essential nutritional
management of deficiencies of these metabolites in COVID-19 disease.
Several recent articles have suggested that the change in prostaglandin profile and the
increase in arachidonic acid derivatives may be indicative of the severity of the disease
and the chances of recovery in the patient with COVID-19.
In addition, the emergence of this new health condition, CPCOVID, has prompted
physiotherapists to renew their search for the best evidence to guide the investigative
and rehabilitative interventions required for this type of patient. Evidence is currently
sparse, but it is known that cognitive function and emotional health are aspects that
need to be considered in the patient's treatment plan, as well as the dynamics of general
condition (weakness, fatigue, concentration, dizziness, headaches, sleep disturbances),
anxiety, debilitating symptoms of decreased aerobic tolerance, and subjective feelings of
severity of asthenia (fatigue, physical and mental tiredness, decreased motivation and
activity). Studies have shown that physical therapy sessions that include: aerobic
exercise, resistance aerobic exercise, strengthening exercises, diaphragmatic breathing
techniques, and mindfulness training are most appropriate for this type of patient.
Moreover, the use of new information and communication technologies (digital health) for
rehabilitation treatment has also proven effective for other diseases such as cardiac,
neurological, respiratory or musculoskeletal disorders.
Objective: To evaluate the improvement in quality of life in CPCOVID patients after a
12-week specialized nutritional intervention with (natural and standardized SPMs
nutritional supplement) together with a therapeutic exercise and education program via
telerehabilitation compared to a group that underwent the tele-rehabilitation program and
no supplements (placebo), as measured by the Quality of Life Scale ( EQ-5D).
Dietary Supplement: Active
Active nutritional supplement plus telerehabilitation
Other: Placebo
Placebo nutritional supplement plus telerehabilitation
Inclusion Criteria:
- To have signed the informed consent form.
- Age between 18 and 70 years with access to and knowledge of basic use of
technological applications.
- Patients with clinical criteria of having suffered from COVID-19 with diagnosis
confirmed by diagnostic techniques and systems in health centers (PCR, rapid antigen
test, and/or serology (positive anti-N antibodies).
- Patients who remain symptomatic for more than 12 weeks after the onset of symptoms.
- Patients who manifest symptoms compatible with CPCOVID since the end of the acute
phase*.
- Patients with fatigue greater than or equal to an average of 4 points on the FSS.
- Independent ambulation, even with the use of technical aids.
Exclusion Criteria:
- Patients with severe neurological diseases at the central and/or peripheral level
that prevent them from following the program.
- Patients with respiratory insufficiency: SaO2 < 90% or respiratory rate ≧30.
- Patients with rheumatic diseases or acute musculoskeletal injuries that do not allow
exercise.
- Patients who do not have access to the Internet or are unable to use the Internet on
a daily basis.
- Patients with clinical symptoms consistent with chronic fatigue syndrome.
- Presence of symptoms consistent with CPCOVID prior to SARS Cov-2 infection.
- Pregnant or lactating women or women of childbearing age who are trying to become
pregnant.
- Patients unable to follow oral and written instructions in Spanish.
- Patients with an allergy to fish, shellfish, or any of the ingredients of the
preparation.
- Patients enrolled in another clinical trial for the treatment of symptomatology
derived from COVID -19.
- Patients who have completed another clinical trial in the 4 weeks prior to
enrollment.
- Patients who have received immunosuppressive medications and/or corticosteroids in
the last 2 weeks prior to enrollment. Patients who have received nonsteroidal
anti-inflammatory drugs (NSAIDs) continuously or on a fixed regimen in the 2 weeks
prior to treatment initiation. Patients who have been taking NSAIDs may have a 7-day
withdrawal period.
- Women of childbearing age who are not willing to take NSAIDs should not be treated.
IIS Aragón
Zaragoza, Spain