As the number of cases of COVID-19 increases, so does information regarding the management and evolution of the disease. 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 . Covid-19 patients without life-threatening symptoms are usually seen in primary care services, with professionals concerned about the limited understanding of the condition and about offering the best available care to these patients . As well as immune modulatory properties, the drug montelukast has antiviral activity against the ZIKA and dengue viruses . Montelukast can also protect against Influenza A virus induced pneumonia by reducing infection of type‐1 alveolar epithelial cells and modulating other proinflammatory mediators . Montelukast blocks the action of leukotrienes C4, D4 and E4 by binding to the CysLT1 receptor in the lungs and bronchi, thus reducing bronchoconstriction and inflammation [5-7].
The case for using montelukast is based on its anti‐inflammatory effect and the activation of the immune system in long term COVID disease. Based on the hypothesis presented, a pilot test was carried out in May 2020. Empirical treatment with montelukast (10 mg / day for 14 days) was started in 12 patients with ”long Covid”, all were women’s. All patients had symptoms lasting more than one month since the start of the clinical presentation. All of these patients had COVID-19 confirmed by PCR. All patients presented dyspnea as the main symptom, followed by asthenia and headache. Other symptoms were fever, skin rashes, amenorrhea, gastrointestinal symptoms and tachycardia. All participants were informed of the off-label use of the drug and written, or oral informed consent was obtained. The patients were followed up by telephone and assessed using a visual analogical scale from 0 to 100 to evaluate clinical improvement.
All patients showed improvement within few days after treatment and a reduction of dyspnea, chest pain, general malaise, dry cough, and nasal symptoms. All of these patients have already been able to return to work after weeks of sick leave. To date, the improvement has been sustained. Recently, three reports discussed some clinical benefits and the potential for off‐label use of montelukast in patients in the acute phase of COVID‐19 [8-10]. A clinical trial is currently on-going . We believe montelukast can also have a beneficial effect on ”long Covid”. Study E (speranza) -COVID-19 will be a phase III, randomized, double-blind, placebocontrolled clinical trial to evaluate the efficacy of montelukast versus placebo to improve the quality of life associated with respiratory symptoms in patients with persistent symptoms of SARS-CoV-2 infection.
We are confident that the results of this trial will offer a valid therapeutic option for the management of ”long Covid”.
Conflict of Interest
- How long does COVID-19 lasts?
- Peel M (2020) What can we tell patients with prolonged COVID-19? BMJ 370: m2923.
- Chen Y, Li Y, Wang X, Zou P (2019) Montelukast, an anti‐asthmatic drug, inhibits Zika virus infection by disrupting viral integrity. Front Microbiol 10: 3079.
- Lin YC, Huang MY, Lee MS, Hsieh CC, Kuo CH, et al. (2018) Effects of montelukast on M2‐related cytokine and chemokine in M2 macrophages. J Microbiol Immunol Infect 51(1): 18‐26.
- Pedersen SF, Ho YC (2020) SARS-CoV-2: a storm is raging. J Clin Invest 130(5): 2202-2205.
- Cardani A, Boulton A, Kim TS, Braciale TJ (2017) Alveolar macrophages prevent lethal influenza pneumonia by inhibiting infection of type‐1 alveolar epithelial cells. PLoS Pathog 13(1): e1006140.
- Cikler E, Ersoy Y, Cetinel S, Ercan F (2009) The leukotriene d4 receptor antagonist, montelukast, inhibits mast cell degranulation in the dermis induced by water avoidance stress. Acta Histochem 111(2): 112‐118.
- Copertino DC, Duarte RRR, Powell TR, Rougvie MM, Nixon DF (2020) Montelukast drug activity and potential against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). J Med Virol.
- Aiello T (2020) Though not FDA approved, off‐label singulair showing promise as coronavirus treatment, say doctors. In: CBS New York.
- Almerie MQ, Kerrigan DD (2020) The association between obesity and poor outcome after COVID‐19 indicates a potential therapeutic role for montelukast. Med Hypotheses 143: 109883.
- The Covid-19 Symptom Montelukast Trial (COSMO). ClinicalTrials.gov (Identifier: NCT04389411).