Recently, a new clinical presentation called "long covid" has been reported, for patients with symptoms lasting for more than 4 weeks from the onset of the disease. Typically, the symptoms comprise dyspnea, cough, headache, arthralgia, fever, abdominal pain, asthenia and skin manifestations This project aims to evaluate the efficacy of Montelukast in improving the quality of life associated with respiratory symptoms in patients with persistent COVID-19 symptoms. The main objective is to compare the efficacy of low-dose Montelukast versus placebo to improve respiratory symptoms in patients with persistent COVID-19 symptoms.
In December 2019, the first case of a new coronavirus causing pneumonia was described in
Wuhan (China), designated as SARS-CoV-2 by the World Health Organization.
From the start of the SARS-CoV-2 alert until May 21st, 2020, 250,287 cases of coronavirus
disease (COVID-19) were reported in Spain. The importance of the COVID-19 pandemic with its
high humanitarian and economic cost, urgently requires effective therapies to reduce the
severity, complications and mortality associated with this infection.
As the number of cases of COVID-19 increases, so does information regarding the management
and evolution of the disease. More recently, a new clinical presentation called "long
COVID-19" has been reported, for patients with symptoms lasting for more than 4 weeks from
the onset of the disease. Typically, the symptoms comprise dyspnea, cough, headache,
arthralgia, fever, abdominal pain, asthenia and skin manifestations.
The inflammatory process produced at the pulmonary and extra pulmonary level, and the immune
response triggered have been identified as important mechanisms in the pathophysiology of
COVID-19.
Coronavirus infection activates the cytokine cascade at the immune level, in which
leukotriene are possibly involved in the development of respiratory symptoms in patients with
persistent symptoms after infection by SARS-CoV-2.
Leukotriene antagonists (LTRAs) have a bronchodilator action and inhibit inflammation of the
airways, resulting in a significant improvement in asthma symptoms and allergic rhinitis. In
asthma, they improve respiratory function, inhalation rate of inhaled β2 agonist, airway
inflammation, airway hyper responsiveness, inhaled corticosteroid dosage, and reduce
exacerbations.
Regarding the treatment of acute SARS-CoV-2 infection, to date, the available evidence is
limited; there are few conclusive clinical trials that allow recommendations based on
scientific evidence.
To date, no treatment has been evaluated in long COVID-19. The hypothesis of using
Montelukast would be based on the pathophysiological response of the disease mediated by the
immune system against the SARS-CoV-2 infection.
Montelukast blocks the action of substances such as leukotriene C4, D4 and E4 by binding to
the CysLT1 receptor in the lungs and bronchi. This reduces the bronchoconstriction caused by
leukotriene and results in less inflammation.
Montelukast effectively attenuated both lung inflammation induced by Lipopolysaccharides in a
mouse model with Acute Respiratory Distress Syndrome, as in human neutrophils.
Individuals affected by long COVID-19 have self-organized to gain visibility. They have made
a self-completed form to describe the characteristics of the disease. The "Persistent
COVID19" network in Catalonia currently gathers more than 3000 people.
From the contact with the "Persistent COVID19 association" in Catalonia, and in search of a
response to this symptomatology, which can be very disabling, a pilot study was carried out
in patients with persistent COVID-19 symptoms with off-label use of Montelukast.
Empirical treatment with Montelukast at a dose of 10 mg / day for 14 days was started in 13
patients with long COVID-19, some with symptoms of more than a month of evolution since the
beginning of the COVID-19 clinic. The patients were followed up to evaluate the improvement
of the symptoms with a numerical scale from 0 to 100 and COPD Assessment Test Scale (CAT), 3
weeks after starting treatment.
An improvement in symptoms was observed a few days after treatment and a good evolution of
the sensation of dyspnea, chest pain, symptoms of discomfort, dry cough, and nasal symptoms.
Likewise, the incorporation of the patients to their work activity during that period was
observed. To date, the improvement continues to exist, without evidence of clinical
deterioration.
Drug: Montelukast
10 mg oral montelukast once daily for 28 days
Other Name: antileukotriene
Other: placebo
10 mg oral placebo once daily for 28 days
Inclusion Criteria:
- Patients 18 to 80 years old with SARS-CoV-2 infection (positive CRP <10 days from the
onset of symptoms) treated in Primary Health Care.
- Persistent respiratory symptoms (more than 1 and <12 months of evolution)
- Mild-moderate dyspnea: score at the beginning of the study according to the modified
Medical Research Council (mMRC) scale from 0 to 3
- The patient must be competent to complement the follow-up evaluations.
- The patient agrees to participate in the study and take assigned medication during the
4 weeks.
- Sign the informed consent
Exclusion Criteria:
- Severity criteria: fever> 38ºC, or O2 saturation <93%.
- Patients with SARS-Cov-2 pneumonia in the acute / subacute phase.
- Patients who have required hospital admission for SARS-Cov-2.
- Chronic Obstructive Pulmonary Disease (COPD), asthma, bronchiectasis, pulmonary
fibrosis, obstructive sleep apnea syndrome (OSAS), chronic respiratory failure from
any cause, home oxygen therapy.
- Use of montelukast or zafirlukast ≤ 30 days prior to inclusion
- Use of any dose of systemic corticosteroids ≤ 30 days prior to inclusion
- Use of gemfibrocil.
- Hypersensitivity to montelukast or to any of the excipients included (e.g. lactose.
- Any condition (including the inability to swallow pills) that, in the opinion of the
researcher, would prevent the completion of taking the medication.
- Active malignancy, current or recent chemotherapy treatment (<6 months).
- Medical history of infection by the Human Immunodeficiency Virus (HIV) or any serious
immunocompromised state.
- Pregnancy, planning to get pregnant or patients of childbearing age not undergoing
birth control methods.
- Breastfeeding mother.
- Any other condition for which, in the opinion of the principal investigator, it is
considered that the subject does not fit the study.
Primaty health Center Corbera
Corbera De Llobregat, Barcelona, Spain
Primary Health Center Jaume Soler
Cornellà De Llobregat, Barcelona, Spain
Primary Health Center 17 Setember
El Prat De Llobregat, Barcelona, Spain
Primary Health Center Camps Blancs
Sant Boi De Llobregat, Barcelona, Spain
Primary Health Center Molí Nou
Sant Boi De Llobregat, Barcelona, Spain
Primary Health Center Vinyets
Sant Boi De Llobregat, Barcelona, Spain
Primary Health Center ElPla
Sant Feliu De Llobregat, Barcelona, Spain
Primary Health Center Raval nord
Barcelona, Spain
Francisco M Mera Cordero, MD
+34699942492
franmcor@hotmail.com
Rosa Morros Pedrós, PhD
+34934824124
rmorros@idiapjgol.org