Síntomas respiratorios leves-moderados en pacientes con COVID-19 persistente: ensayo clínico y caracterización biológica de Montelukast (E-SPERANZA COVID)

The coronavirus disease-2019 (COVID-19) has recently emerged as a new pandemic. As the number of cases increases, it has become clear that many patients may develop lasting symptoms that can have disabling consequences. Although a big progress has been made in treatment and knowledge of the underlying causes in the acute phase of SARS-CoV-2, there is much that remains unknown in long COVID and, to date, there is no available treatment. The global objective of this project is to generate evidence on the clinical, biological characterization and treatment of long COVID-19.

We specifically aim to assess the efficacy of montelukast in a double-blind randomized clinical trial, placebocontrolled, in mild-moderate respiratory symptoms in patients with long-COVID. As secondary objectives, we aim to assess the effect of montelukast versus placebo on improving exercise capacity,exertional oxygen desaturation, use of healthcare resources, mortality, side effects, and days of work sick leave and, to assess whether antinuclear antibodies are predictors of response to montelukast.

In a subset of patients we aim:

a) To characterize mechanisms involved in persistent respiratory symptoms (dyspnoea with/without cough);

b) To immunologically characterize long Covid-19: presence of different Interferon neutralizing antibodies, different immune variables (lymphoid subpopulations, immunoglobulins and cytokines) and to identify activated immune response pathways and

c) To evaluate presence of SARS-CoV-2 in stool samples and the impact of microbiota alterations among long COVID-19 patients and the potential restoration after montelukast treatment. We aim to offer a treatment to persons suffering long COVID-19 in improving respiratory symptoms.

The possibility to correlate different biological markers with clinical symptoms in a disease in which much can help to comprise the phenotypes of the illness. The comprehensive baseline characterization (respiratory parameters and microbiological and immunological biomarkers) in a subset of patients will add information about the potential underlying causes and mechanisms of the disease in relation with clinical symptoms. It will also allow us to understand the response to montelukast, and it may contribute to identify potential therapeutic targets and new treatments to prevent or reduce the effects of persistent symptoms or to help recovery. The results of the study will be quick implementation into the clinics. These results will be disseminated in conferences and publications. Furthermore, this clinical research and therapeutic repositioning study and oriented to the clinical practice in relation to the efficiency of pharmacological treatments will allow a quick implementation of the results into the clinic.