This study aims to evaluate the impact of a non-pharmacological treatment (nutritionaltherapy and pulmonary rehabilitation) on endothelial function, body composition, andphysical functionality in recovered COVID-19 patients.The primary research question is: What is the effect of a non-pharmacological treatment(nutritional therapy and pulmonary rehabilitation) on endothelial function, bodycomposition, and physical capacity in recovered COVID-19 patients, compared to thosereceiving conventional medical management? A nutritional treatment combined withL-citrulline supplementation (intervention group) will be compared against conventionaltreatment alone (control group). Both groups will undergo pulmonary rehabilitation for a3-month follow-up.Subjects assigned to the intervention group will be required to: - Take 4 g of L-citrulline daily for 3 months. - Attend an interim session at 1.5 months for review of the nutritional treatment and supplementation. - Keep a record of each supplement intake.
Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, represents a global public
health crisis that has resulted in severe complications and death in more than 500,000
individuals worldwide.
The risk factors for severe COVID-19 include age over 70 years, hypertension, diabetes
mellitus, smoking, coronary artery disease, and obesity, which have been associated with
endothelial dysfunction (ED). The coexistence of chronic non-communicable diseases
significantly exacerbates the inflammatory response, increasing the risk of adverse
events and poor prognosis. Similarly, a high probability of cardiovascular diseases in
subjects is at elevated risk of severe COVID-19, due to the overexpression of
angiotensin-converting enzyme 2. In addition, in our country, the leading causes of death
are related to metabolic diseases: 19% of men and women between the ages of 30 and 69 die
from cardiovascular diseases, with diabetes ranking as the second leading cause of death.
Furthermore, 76.6% of the population is overweight or obese, and 25.5% has hypertension,
factors that render our population particularly susceptible to moderate to severe
COVID-19.
Moreover, both pharmacological and non-pharmacological treatments have primarily focused
on the acute phase of infection. However, it is essential to implement treatment
protocols, including pulmonary rehabilitation and nutritional therapy with citrulline
supplementation or immunonutrients with anti-inflammatory properties, to prevent
Post-Intensive Care Syndrome, reduce systemic inflammation, and improve endothelial
function. These interventions may collectively enhance protein synthesis, attenuate
muscle mass loss, and promote patient autonomy, functional recovery, and overall quality
of life.
Post-COVID-19 syndrome Post-COVID-19 syndrome has been defined as the persistence of
symptoms and/or delayed long-term remission of complications arising from SARS-CoV-2
infection, occurring beyond 4 weeks after initial symptom onset.
Nutritional supplementation L-citrulline L-Citrulline is a non-essential, water-soluble
alpha-amino acid and a potent endogenous precursor of L-arginine, which increases the
bioavailability of NO. In endothelial cells, NO is synthesized from L-arginine by
endothelial nitric oxide synthase, yielding NO and L-citrulline.
Endothelial dysfunction ED is a systemic condition in which the endothelium loses its
physiological properties, including vascular permeability, vascular tone regulation, and
neutrophil recruitment, thereby promoting a prothrombotic, proinflammatory, and
pro-oxidant state.
General objective:
To evaluate the impact of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on endothelial function, body composition, and physical
functionality in recovered COVID-19 patients.
Specific objectives:
To evaluate the impact of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on endothelial function in recovered COVID-19 patients.
To evaluate the impact of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on body composition in recovered COVID-19 patients.
To evaluate the impact of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on physical functionality in recovered COVID-19 patients.
To evaluate the impact of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on quality of life in recovered COVID-19 patients.
Secondary objectives:
To describe the prevalence of sarcopenia in recovered COVID-19 patients. To describe
cardiovascular alterations in recovered COVID-19 patients. To describe alterations in
body composition in recovered COVID-19 patients. To describe metabolic alterations in
recovered COVID-19 patients. To evaluate the effect of a non-pharmacological intervention
(nutritional therapy and pulmonary rehabilitation) on muscle strength in recovered
COVID-19 patients.
To evaluate the effect of a non-pharmacological intervention (nutritional therapy and
pulmonary rehabilitation) on pulmonary function in recovered COVID-19 patients.
Dietary Supplement: L-citrulline supplementation
Subjects allocated to the intervention group receive 4 grams of L-citrulline
supplementation daily, combined with nutritional therapy, over a 3-month period.
Inclusion Criteria:
- Recovered COVID-19 patients with a negative PCR test for SARS-CoV-2.
- Subjects between 40 and 80 years.
- Subjects who give written informed consent to participate in the study.
Exclusion Criteria:
- Subjects diagnosed with Human Immunodeficiency Virus (HIV).
- Subjects diagnosed with cancer.
- Subjects with a glomerular filtration rate (GFR) <30 ml/min/1.73 m².
- Subjects currently enrolled in another interventional study.
Instituto Nacional de Enfermedades Respiratorias
Mexico City, Mexico
Not Provided