key: cord-0877046-me8qo554 authors: Fidan, Cihan; Aydoğdu, Ayşe title: As a potential treatment of COVID-19: Montelukast date: 2020-05-11 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.109828 sha: 50dc7bf7e9f62752bb0fc4aca376cc7181995b9f doc_id: 877046 cord_uid: me8qo554 It has been hypothesized that Montelukast, a cysteinyl leukotriene (cysLT) receptor antagonist, with effects of anti-inflammatory, suppress oxidative stress and reduce affect cytokine production, may limited progression of the disease on COVID-19 infection. To the Editor: The pandemia, emerged with the new coronavirus 2019 (COVID-19), has not yet been brought under control, despite serious measures taken all over the world and efforts to control and treat the disease. Up till now, a specific treatment for COVID-19 infection is not available. We believe that new approaches to treatment should be considered in cases of COVID-19. Here, the treatment approach of COVID-19 infection may include monteluksat, a cysteinyl leukotriene (cysLT) receptor antagonist, and the possibility of decrease severe COVID-19 progression will be mentioned. The clinical process features of COVID-19 can range from asymptomatic cases to acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. The disease can progress to pneumonia, respiratory failure and death when severe, and in this case, acute complications include acute lung injury, ARDS, sepsis and shock. This progression is thought to be related to excessive increase in proinflammatory cytokine levels (1, 2). In addition, as it is known, COVID-19 reaches the cell through angiotensin-converting enzyme (ACE) receptors and leads to severe pneumonia and thus increased mortality rates during infection by binding to human ACE2 (3, 4) . The cough that can develop with ACE inhibition is caused by increased bradykinin and its bronchoconstrictor effect, and montelukast, a selective LTD4 antagonist, has an inhibitory effect on bradykinin-induced airway hypersensitivity (5, 6) . Although it is unclear how this effect came about, it is thought to be through ACE receptors. The most important cause of COVID-19 related deaths is respiratory failure, which is progressive and unresponsive to treatment (2, 4) . ARDS, which frequently occurs in these patients, is an acute inflammatory lung injury, a clinical condition that is not well understood due to its complex pathogenesis, and is a result of widespread alveolar injury caused by intense inflammation. IL-6 and IL-8, the tumor necrosis factor (TNF) and IL-1 produced in the early phase and other pro-inflammatory cytokines that occur in the later stages of the disease, induce leukocyte migration to the region. Then, leukocytes accumulating in the lungs are activated and secretive reactive oxygen species and proteases that damage capillary endothelium and alveolar epithelium. Montelukast therapy has been shown in recent studies to reduce TNF-α, IL-6 and IL-1b levels (3, 4) . The pronounced inhibitory effect of montelukast against bradykinin-induced tracheal smooth muscle contraction has also been demonstrated, which supports the interaction between bradykinin and leukotriene mediators (3, 6) . Montelukast is a potent cysteinyl leukotriene (cysLT) receptor antagonist with antiinflammatory effects and has been proven to significantly suppress oxidative stress. Also, CysLTs can affect cytokine production. In high doses and i.v. administration of montelukast, IL-4, IL-5, IL-13 reduced protein expression in the lungs exerts its anti-inflammatory effect through the suppression of T-helper type-2 cytokines. Consequently, use of high-dose montelukast as an anti-inflammatory agent has been shown to be effective in acute asthma (7). In addition, the use of montelukast is known to have a decreasing effect on the frequency and severity of wheezing in patients with clinical episodic wheezing (wheezing after an upper respiratory tract infection caused by adenovirus, influenza, metapneumovirus, coronavirus). In these patients, montelukast does not prevent these viral infections, but seems to limit the upper respiratory tract (5, 8) . In the light of these informations, montelukast has an effect on events developing with ACE receptors, and also has an anti-inflammatory effect with bradykinin and leukotriene antagonism; Because of COVID-19 has entry into the cell through ACE receptors and caused mortality due to excessive inflammatory processes, it was thouht that montelukast may have a limiting effect on the progression of the disease on COVID-19 infection. It suggests that it may be effective to use it, possibly at high doses, in order to reduce its severity during the course of the disease or before the disease occurs fully in people at risk. The healing effects of montelukast on these damages can be seen. I/We certify that the manuscript represents valid work and that neither this manuscript nor one with substantially similar content under my/our authorship has been published or is being considered for publication elsewhere. For papers with more than one author, we agree to allow the corresponding author to serve as the primary correspondent with the editorial office, to review the edited typescript and proof. I/We have seen and approved the submitted manuscript. All of us have participated sufficiently in the work to take public responsibility for the contents. All the authors have made substantial contributions to the intellectual content of the paper and fulfil at least 1 condition for each of the 4 categories of contributions: Category 1 (conception and design, acquisition of data, analysis and interpretation of data), Category 2 (drafting of the manuscript, critical revision of the manuscript for important intellectual content), Category 3 (final approval of the version to be published) and Category 4 (Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved). I/We also certify that all my/our affiliations with or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript are completely disclosed on the title page of the manuscript. My/our right to examine, analyze, and publish the data is not infringed upon by any contractual agreement. I/We certify that all persons who have made substantial contributions to the work reported in this manuscript (e.g., data collection, writing or editing assistance) but who do not fulfil the authorship criteria are named along with their specific contributions in an acknowledgment section in the manuscript. I/We also certify that all persons named in the acknowledgment section have provided written permission to be named. OR (If an acknowledgment section is not included) No other person has made substantial contributions to this manuscript. The author(s) undersigned hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership, including any and all rights incidental thereto, exclusively to the Medical Hypotheses, in the event that such work is published in Medical Hypotheses. We grant the journal the right to analyze the information Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel medicine and infectious disease Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan Medical science monitor : international medical journal of experimental and clinical research COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clinical and experimental rheumatology Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children. American journal of respiratory and critical care medicine Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig None. The authors declare that they have no competing interests. None.obtained from submitted manuscripts as part of editorial research to improve the peer-review process, and for teaching and training activities.We warrant that the work is original and it contains no libellous statements, that it contains nothing unlawful, and does not infringe upon any copyright, trademark, patent, statutory right, proprietary right of others, and that I shall indemnify the editors against any costs, expenses and damages arising from any breach of this warranty. We understand that the view and opinions expressed in the article are of the authors and not of the journal.