The Effect of Montelukast Treatment on Elderly Patients Diagnosed with COVID-19

Year 2024, , 435 - 439, 31.08.2024

Oğuzhan Zengin , Öztuğ Aytekin , Mustafa Doğru , Burak Göre , Emine Sena Sözen , Merve Evli , Enes Seyda Şahiner , Osman İnan , İhsan Ateş

https://doi.org/10.54005/geneltip.1352153

Abstract

Background/Aims: The clinical course in COVID-19 patients can vary from asymptomatic cases to acute respiratory distress syndrome (ARDS), respiratory failure and multiorgan dysfunction. Clinical progression is thought to be mainly due to the release of proinflammatory cytokines. The most common symptoms are fever, cough, malaise, and shortness of breath. Montelukast, which is used in the treatment of seasonal allergic rhinitis and asthma, has brought its use in COVID-19 infection due to its anti-inflammatory and cytokine secretion-reducing effect. There are many studies in the literature that montelukast treatment has a positive effect on the prognosis and mortality of COVID-19. However, there are not enough studies evaluating the efficacy of montelukast treatment in elderly patients. The aim of our study is to evaluate the clinical and laboratory efficacy of montelukast treatment in patients aged 60 and over in COVID-19 disease, and to indicate the differences from the studies in the literature.
Methods: Our research was planned as a retrospective, single-center, observational study. The medical records of 75 COVID-19 patients aged 60 and over who were hospitalized in the internal medicine clinic of Ankara Bilkent City Hospital between September 2021 and December 2022 were included. Diagnosis of COVID-19 was confirmed with a reverse transcription polymerase chain reaction (RT-PCR) test from nasopharyngeal swab.
Results: Clinical findings and results were compared between the patients who received montelukast and the control group. There was no statistically significant difference between the two groups in terms of cough, dyspnea, gastroenteritis and oxygen theraphy requirement. There is no significant difference between the two groups in terms of the need for intensive care unit admission and mortality. The length of hospital stay was compared in both groups, it was 10.88±7.24 days in the control group and 10.51±5.44 days in the montelukast group, and there was no statistically significant difference between the groups. The laboratory parameters of the patients in both groups were compared. The neutrophil count and leukocyte count measured before hospitalization were found to be significantly lower in the patient group receiving montelukast (p=0.022, p=0.016). No significant difference was found in other laboratory parameters.
Conclusions: Although montelukast treatment has positive effects on prognosis in COVID-19 disease in the literature, a similar effect was not observed in the population aged 60 and over in our study. We did not find the positive effect of short-term montelukast treatment on the prognosis of patients aged 60 years and older who were hospitalized due to COVID-19. We thought that this was due to the low efficacy of montelukast in the elderly population. Our study is one of the first to examine montelukast therapy in the geriatric population with COVID-19.

Keywords

COVID-19, Montelukast, Elderly, Geriatrics, SARS-CoV-2

COVID-19 Tanısı Konan Yaşlı Hastalarda Montelukast Tedavisinin Etkisi

Abstract

Amaç: COVİD-19 hastalarında klinik seyir asemptomatik vakalardan akut solunum sıkıntısı sendromuna (ARDS), solunum yetmezliğine ve çoklu organ fonksiyon bozukluğuna kadar değişebilmektedir. Klinik ilerlemenin temel olarak proinflamatuar sitokinlerin salınımına bağlı olduğu düşünülmektedir. En sık görülen semptomlar ateş, öksürük, halsizlik ve nefes darlığıdır. Mevsimsel alerjik rinit ve astım tedavisinde kullanılan montelukast, antiinflamatuar ve sitokin salgısını azaltıcı etkisi nedeniyle COVİD-19 enfeksiyonunda da kullanımını gündeme getirmiştir. Literatürde montelukast tedavisinin COVİD-19'un prognozu ve mortalitesi üzerine olumlu etkisi olduğunu gösteren pek çok çalışma bulunmaktadır. Ancak yaşlı hastalarda montelukast tedavisinin etkinliğini değerlendiren yeterli çalışma bulunmamaktadır. Çalışmamızın amacı, COVİD-19 hastalığında 60 yaş ve üzeri hastalarda montelukast tedavisinin klinik ve laboratuvar etkinliğini değerlendirmek ve literatürdeki çalışmalardan farklılıklarını ortaya koymaktır.
Metod: Araştırmamız retrospektif, tek merkezli, gözlemsel bir çalışma olarak planlandı. Eylül 2021 ile Aralık 2022 tarihleri ​​arasında Ankara Bilkent Şehir Hastanesi dahiliye kliniğinde yatarak tedavi gören 60 yaş ve üzeri 75 COVİD-19 hastasının tıbbi kayıtları dahil edildi. COVID-19 tanısı nazofaringeal sürüntüden alınan ters transkripsiyon polimeraz zincir reaksiyonu (RT-PCR) testiyle doğrulandı.
Bulgular: Montelukast alan hastalar ile kontrol grubu arasında klinik bulgular ve sonuçlar karşılaştırıldı. Öksürük, dispne, gastroenterit ve oksijen tedavisi gereksinimi açısından iki grup arasında istatistiksel olarak anlamlı fark yoktu. Yoğun bakıma yatış ihtiyacı ve mortalite açısından iki grup arasında anlamlı fark yoktu. Hastanede kalış süreleri her iki grupta karşılaştırıldığında kontrol grubunda 10,88±7,24 gün, montelukast grubunda 10,51±5,44 gün olup gruplar arasında istatistiksel olarak anlamlı fark saptanmadı. Her iki gruptaki hastaların laboratuvar parametreleri karşılaştırıldı. Montelukast alan hasta grubunda hastaneye yatmadan önce ölçülen nötrofil sayısı ve lökosit sayısı anlamlı olarak düşük bulundu (p=0,022, p=0,016). Diğer laboratuvar parametrelerinde anlamlı bir fark bulunamadı.
Sonuç: Literatürde montelukast tedavisinin COVİD-19 hastalığında prognoza olumlu etkileri olmasına rağmen çalışmamızda 60 yaş ve üzeri popülasyonda benzer bir etki gözlenmedi. Kısa süreli montelukast tedavisinin COVİD-19 nedeniyle hastaneye yatırılan 60 yaş ve üzeri hastaların prognozlarına olumlu etkisini bulamadık. Bunun yaşlı popülasyonda montelukastın etkinliğinin düşük olmasından kaynaklandığını düşündük. Çalışmamız, COVID-19'lu geriatrik popülasyonda montelukast tedavisini inceleyen ilk çalışmalardan biridir.

Keywords

COVID-19, Montelukast, Yaşlı, Geriatri, SARS-CoV-2

References

• Khan, Ahsan R., et al. "Montelukast in hospitalized patients diagnosed with COVID-19." Journal of Asthma 59.4 (2022): 780-786.
• Fidan, Cihan, and Ayşe Aydoğdu. "As a potential treatment of COVID-19: Montelukast." Medical hypotheses 142 (2020): 109828.
• Rodriguez-Morales AJ, Cardona-Ospina JA, Gutierrez-Ocampo E, Villamizar-Pena R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis 2020:101623. PubMed PMID: 32179124. Epub 2020/03/18. eng.
• Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020. PubMed PMID: 32077115. Epub 2020/02/23. eng.
• Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, Liu L, Shan H, Lei C-L, Hui DSC, China Medical Treatment Expert Group for Covid-19, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi:10.1056/nejmoa2002032.
• Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620– 2629. doi:10.1172/JCI137244.
• Pedersen SF, Ho YC. SARS-CoV-2: a storm is raging. J Clin Invest. 2020;130(5):2202–2205. doi:10.1172/ JCI137647.
• Chen X, Zhang X, Pan J. Effect of Montelukast on Bronchopulmonary Dysplasia (BPD) and Related Mechanisms. Medical science monitor : int Med J Exp Clin Res 2019 Mar 13; 25: 1886-93. PubMed PMID: 30862773. Pubmed Central PMCID: PMC6427930. Epub 2019/03/14. eng.
• Sarzi-Puttini P, Giorgi V, Sirotti S, Marotto D, Ardizzone S, Rizzardini G, et al. COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol 2020;38(2):337–42. PubMed PMID: 32202240. Epub 2020/03/2eng.
• Erfen, Şebnem, and Esin Akbay Çetin. "Therapeutic and Preventive Effects of Piperine and its Combination with Curcumin as a Bioenhancer Against Aluminum-Induced Damage in the Astrocyte Cells." Neurotoxicity Research (2022): 1-19.
• Mullol J, Callejas FB, Méndez-Arancibia E, Fuentes M, Alobid I, Martinez-Anton A, Valero A, Picado C, Roca-Ferrer J. Montelukast reduces eosinophilic inflammation by inhibiting both epithelial cell cytokine secretion (GM-CSF, IL-6, IL-8) and eosinophil survival.
• Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020;55(4):2000607. doi:10.1183/13993003.00607-2020.
• Bisgaard H, Flores-Nunez A, Goh A, Azimi P, Halkas A, Malice MP, et al. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children. Am J Respir Critical Care Med 2008;178(8):854–60. PubMed PMID: 18583576. Epub 2008/06/28. eng.
• Noor A, Najmi MH, Bukhtiar S. Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig. Indian J Pharmacol 2011;43(4):445–9. PubMed PMID: 21845003. Pubmed Central PMCID: PMC3153711. Epub 2011/08/17. eng.
• Davino-Chiovatto JE, Oliveira-Junior MC, MacKenzie B, Santos-Dias A, Almeida-Oliveira AR, Aquino-Junior JCJ, Br ito AA, R igonato-Oliveira NC, Damaceno-Rodrigues NR, Oliveira APL, et al. Montelukast, leukotriene inhibitor, reduces LPS-induced acute lung inflammation and human neutrophil activation. Arch Bronconeumol. 2019;55(11):573–580. doi:10.1016/j.arbres.2019.05.003
• CBS New York. Though Not FDA Approved, Off-Label Singulair Showing Promise As Coronavirus Treatment, Say Doctors. 2020.
• Aigner, Ludwig, et al. "The leukotriene receptor antagonist montelukast as a potential COVID-19 therapeutic." Frontiers in molecular biosciences 7 (2020): 610132.
• Kerget, Buğra, et al. "Effect of montelukast therapy on clinical course, pulmonary function, and mortality in patients with COVID‐19." Journal of Medical Virology 94.5 (2022): 1950-1958.
• Sanghai, Nitesh, and Geoffrey K. Tranmer. "Taming the cytokine storm: repurposing montelukast for the attenuation and prophylaxis of severe COVID-19 symptoms." Drug discovery today 25.12 (2020): 2076-2079.
• Columbo, Michele. "Asthma in the elderly: a double-blind, placebo-controlled study of the effect of montelukast." Asthma research and practice 3 (2017): 1-4.
• Bozek, Andrzej, and Janne Winterstein. "Montelukast’s ability to fight COVID-19 infection." Journal of Asthma 58.10 (2021): 1348-1349.
• Korenblat, Phillip E., et al. "Effect of age on response to zafirlukast in patients with asthma in the Accolate Clinical Experience and Pharmacoepidemiology Trial (ACCEPT)." Annals of Allergy, Asthma & Immunology 84.2 (2000): 217-225.
• Horiguchi T, Tachikawa S, Kondo R, et al. Comparative evaluation of the leukotriene receptor antagonist pranlukast versus the steroid inhalant fluticasone in the therapy of aged patients with mild bronchial asthma. Arzneimittelforschung. 2007;57(2):87–91.
• Scicolone, Nicola, et al. "Safety and efficacy of montelukast as adjunctive therapy for treatment of asthma in elderly patients." Clinical Interventions in Aging (2013): 1329-1337.
• Bäck, Magnus. "Leukotriene signaling in atherosclerosis and ischemia." Cardiovascular drugs and therapy 23 (2009): 41-48.
• Russmann S, Iselin HU, Meier D, et al. Acute hepatitis associated with montelukast. J Hepatol. 2003;38(5):694–695
• Sánchez G, Buitrago D. Effect of Montelukast 10 mg in Elderly Patients with Mild and Moderate Asthma Compared with Young Adults. Results of a Cohort Study. Open Respir Med J. 2018;12:67-74. Published 2018 Nov 14. doi:10.2174/1874306401812010067