|
 
 |
| CASE REPORT |
|
| Year : 2021 | Volume
: 15
| Issue : 1 | Page : 31-35 |
|
Effects of montelukast on clinical manifestations of coronavirus infection: A clinical observation among six patients
Ram B Singh1, Ghizal Fatima2, Saibal Chakravorty3
1 Department of Cardiology, Halberg Hospital and Research Institute, Moradabad, Uttar Pradesh, India
2 Department of Cardiology, Era's Lucknow Medical College, Lucknow, Uttar Pradesh, India
3 Department of Cardiology, Metro Multispeciality Hospital, Noida, Uttar Pradesh, India
| Date of Submission | 22-Jan-2022 |
| Date of Decision | 03-Feb-2022 |
| Date of Acceptance | 26-Jan-2022 |
| Date of Web Publication | 13-Apr-2022 |
Correspondence Address:
Dr. Ghizal Fatima
Era's Lucknow Medical College, Lucknow, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/upjimi.upjimi_3_22
Montelukast is an antiviral agent and anti-inflammatory agent used in the treatment of pro-inflammatory pulmonary diseases. Since coronavirus infection disease 2019 (COVID-19) involves mainly lung in majority of the patients, it may have a possible benefit among these patients. This report aims to emphasize about the role of montelukast in COVID-19 patients. After verbal consent and clearance from the ethics committee, all the patients (n = 6) presenting with common cold, fever, cough, and breathlessness, who were administered montelukast, were considered for entry to this study. The diagnosis of COVID-19 was confirmed via a positive reverse transcription-polymerase chain reaction test among all the patients. All the patients were given standard treatment including hydroxychloroquine 200 mg twice daily day 1 and then 200 mg daily for 5 days, azithromycin 250–500 mg twice daily for 7 days, Vitamin C 500 mg daily, and Zincovit 1 tablet daily for about 3 weeks. Clinical, radiological, and blood examinations were done in all the patients included in this report. All the patients were adults between 34 and 70 years, 3 females, and presented with fever, cough, breathlessness, and body ache simulating a respiratory tract viral infection. They were initially treated with levocetirizine and montelukast 10–20 mg twice or thrice daily, depending upon clinical status of these patients. Those patients who had lower oxygen saturation below 90% (n = 2) were also administered oxygen and cortisone (n = 2) for possible benefit. Only one patient was hospitalized and one was on noninvasive ventilation for 5 days due to lower oxygen saturation below 70%. All patients recovered. All patients received standard treatment for COVID-19, hence it is not clear that which treatment had provided the benefit. Since all patients received montelukast and only one was hospitalized, it poses the possibility that the role of montelukast should be examined in a large number of patients in phase II and phase III trials.
Keywords: Anti-inflammatory, antioxidant, antiviral, viral infection
How to cite this article:
Singh RB, Fatima G, Chakravorty S. Effects of montelukast on clinical manifestations of coronavirus infection: A clinical observation among six patients. J Intern Med India 2021;15:31-5 |
How to cite this URL:
Singh RB, Fatima G, Chakravorty S. Effects of montelukast on clinical manifestations of coronavirus infection: A clinical observation among six patients. J Intern Med India [serial online] 2021 [cited 2023 Mar 24];15:31-5. Available from: http://www.upjimi.com/text.asp?2021/15/1/31/343029 |
| Introduction | |  |
The association of coronavirus infection disease 2019 (COVID-19) and severe complications and mortality including cardiovascular and neurological sequelae, especially acute myocardial infarction and thrombosis, aroused global attention since its outbreak in 2019.[1],[2] In the first 6 months of the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has infected nearly 20 million people.[2] Currently, there are no vaccines or specific therapeutic drugs clinically approved for treatments of COVID-19, although remdesivir appears to be beneficial.[1],[2] However, the drugs used for treating COVID-19 in pregnant women, as well as in children and the elderly, require a higher safety profile. Here, we identified an anti-asthmatic drug, montelukast (MK), which is of safety profile for pregnant women and exhibited antiviral efficacy against ZIKV infection in vitro and in vivo.[3],[4] It has been shown that montelukast can disrupt the integrity of the virions by releasing the viral genomic RNA, which results in to irreversible inhibition of infectivity of the virus. In view of the potential anti-inflammatory, anti-asthmatic, and neuroprotective activity observed with the use of montelukast reported earlier, it is promising that montelukast could be used for patients with coronavirus infection, particularly for mild-to-moderate cases and in pregnant women, where other antiviral agents may not be safe.[3] MK, a selective leukotriene D4 receptor antagonist, is administered mainly to reduce eosinophilic inflammation in asthmatic patients.[4] The primary objective of this study is to highlight novel additional targets for MK besides the pulmonary inflammation and to emphasize its anti-inflammatory and antioxidant potential. In this viewpoint, we report clinical observations in five cases of COVID-19, proven by reverse transcription-polymerase chain reaction (RT-PCR) test, in which MK was administered, to prevent persistent common cold, cough, and dyspnea and because it appears to be much more than an antiasthma drug
| Case Reports | | |
Case 1
A 55-year-old woman suffering from hypertension and diabetes presented with fever, cough, weakness, and sweating of about 3-day duration. She had high blood sugar levels. The blood pressures and fasting blood sugar levels were controlled in the previous weak but became erratic for the last 4 days. Physical examination revealed temperature 101°C, pulse 122/min, and blood pressure 185/100 mmHg. Systemic examination revealed bilateral mild crepts with rhonchi. Her oxygen saturation was 95%. Further systemic examination revealed no abnormality.
Laboratory data showed random blood glucose levels to be 355 mg/dl, total leukocyte counts levels 14.532; with differential leukocyte counts measuring neutrophil 91%, lymphocyte 8%, eosinophil 1, and monocyte 1%. Total lymphocyte count cells 77/1000, that is directly indicating lymphopenia. She was administered standard therapy along with levocetirizine 5 mg twice daily and montelukast 10 mg twice daily along with metformin 1000 mg twice daily, Amaryl 3 mg daily, and telmisartan 40 mg daily. She was also administered 40 units of Mixtard daily along with oral hypoglycemic agents. She remained in isolation for 1 week, during which all medications continued, after which she was advised to continue inhaler and montelukast, 10 mg twice daily. She recovered in 3 days.
Case 2
A 70-year-old man, body weight 77 kg, presented with fever, weakness, persistent coughing, and breathlessness for about 10-day duration. He had a history of chronic bronchitis in the past few years with diabetes mellitus for the last 10 years. Physical examination revealed temperature 101°C, pulse 105/min, and blood pressure 140/100 mmHg. Systemic examination revealed bilateral crepts and rhonchi on auscultation of the chest. His blood test also showed leukocytosis 18,523, polymorph 84, lymphocyte 13, eosinophil 3, monocyte 0, and blood glucose postprandial 165 mg/dl.
He was administered standard therapy along with levocetirizine 10 mg and montelukast 20 mg twice daily for 10 days and then I tab twice daily for another 10 days due to persistent cough and dyspnea. She recovered in 7 days.
Case 3
A 59-year-old, 67-kg female presented with cough, fever, and dyspnea of 5-day duration. She had diabetes mellitus for the last 8 years and got infection while in contact with her husband suffering from COVID-19. Physical examination revealed pulse 120/min, BP 178/90 mmHg, and temperature 101°C. Her oxygen saturation was 90%. Systemic examination revealed crepitation and rhonchi in the chest with prominent bronchovascular marking on radiographic examination of lungs. Her total leukocyte count was 17,630, polymorph 87, lymphocyte 11, monocyte 2, ESR 33 mm, and high-sensitive C-reactive protein 8.8 μg/ml.
She was administered standard therapy along with levocetirizine 10 mg and montelukast 20 mg thrice daily due to severe asthmatic presentation. She was also given injection solumedrol, 40 mg twice daily for 5 days, because there was no relief in dyspnea. She was given 40 units of injection Mixtard-30/70 and insulin daily to maintain the blood glucose below 120 mg/dl fasting and below 150 mg/dl postprandial blood glucose. She recovered in 10 days.
Case 4
A 34-year-old woman presented with marked weakness, pain and itching in eyes, and nervousness, restlessness, and pain in the body, with mild fever with history of contact with a COVID-19 patient. Physical examination revealed body weight 65 kg, temperature 99.5°C, pulse 98/min, blood pressure 98/72 mmHg, breathing rate 20/min, and oxygen saturation 98%. Systemic examination showed that examination of the lung, heart, nervous system, and abdomen revealed no abnormality. She got infected while living in the same house with cases 2 and 3.
Laboratory data revealed polymorph 85%, lymphocyte 14%, monocyte 1%, and high-sensitive C-reactive protein 3.5 ug/dl. Apart from standard treatment, she was administered levocetirizine 5 mg and montelukast 10 mg twice daily for 1 week due to mild cough and cold. She recovered in 5 days.
Case 5
A 26-year-old male presented with marked breathlessness, restlessness, and fever with semi-consciousness of 1-day duration. Past history revealed that he had high fever 3 days ago which was relieved by paracetamol and antibiotics given for 3 days. Physical examination revealed pulse 144/min, blood pressure 150/100 mmHg, and oxygen saturation 45% with semi-consciousness. Systemic examination revealed bilateral crepts and rhonchi on auscultation of the chest. X-ray chest showed prominent bronchovascular markings without any features of infiltration or pneumonia in the radiogram. Laboratory data showed random blood glucose levels to be 355 mg/dl, total leukocyte counts levels 14.532; with differential leukocyte counts measuring neutrophil 91%, lymphocyte 8%, eosinophil 1, and monocyte 1%. Her random blood glucose was 109 mg/dl and hs creative protein s 3.3 μg/dl.
Apart from standard therapy, he was given injection Dexona 1 vial intravenously 4 hourly, along with injection ceftriaxone 1 g intravenously 2 hourly, levocetirizine 10 mg 4 hourly, and montelukast 20 mg 4 hourly. She recovered in 10 h.
Case 6
A 55-year-old man presented with fever, cough, and common cold with mild breathlessness for 10-day duration. Past history revealed that he suffered from hypertension and angina about 2 years ago, for which he was hospitalized and treated. On examination, his oxygen saturation was 65%, blood pressure 90/65 mmHg, and pulse rate 125/min. His RT-PCR test was positive for the diagnosis of COVID-19. He was administered doxycycline 100 mg twice daily, levocetirizine 10 mg thrice daily, and montelukast 20 mg thrice daily along with dexamethasone 4 mg 4 hourly and oxygen showing no improvement. He was put on noninvasive ventilation for 5 days in the intensive care unit and was administered remdesivir, doxycycline, low-molecular-weight heparin, and rosuvastatin 20 mg daily, along with clopidogrel 75 mg daily, while in intensive care. He showed improvement in oxygen saturation and general condition after 5 days in intensive care while continuing montelukast during the follow-up of another 1 week.
| Treatment | | |
All the six patients were administered standard therapy as per guidelines for treatment of COVID-19: azithromycin (500 mg twice daily), hydroxychloroquine (400 mg on the 1st day and 200 mg daily for 5 days), Vitamin C 500 mg/day, and Zincovit one capsule daily (composition: minerals (zinc, copper, iodine, magnesium, manganese, molybdenum, selenium, and chromium) + vitamins (A, B1, B2, B3, B5, B6, B7, B9, B12, C, D3, and E). One tablet provides 63 mg zinc sulfate). Cases 5 and 6 who presented with respiratory failure were also administered dexamethasone 4 mg 4–8 hourly daily for few days and then tapered in another 3–5 days. In all the cases, the diagnosis of COVID-19 was confirmed by positive RT-PCR test.
| Comments | | |
This clinical observation indicates that in patients with COVID-19, treatment with MK may have provided possible benefits, resulting in rapid recovery, although they were also administered standard therapy. Since there is no suitable antiviral drug therapy available for treatment of COVID-19, it is possible that MK should be further evaluated for its antiviral effects via in vitro experiments as well as in randomized, controlled trials. The possible benefits provided by treatment with MK may be due to its anti-inflammatory, antioxidant, and possible antiviral activity against COVID-19 infection. The antivirus activity of MK has already been proven in Zika virus (ZIKV) infection.[3],[4],[5] The antiviral activities of MK against ZIKV and other two flaviviruses, DENV and YFV, in vitro were proven and MK also exhibited protective efficacy against ZIKV vertical transmission and lethal challenge[3] [Figure 1]. | Figure 1: (a-g) Chemical structure of montelukast showing free oxygen radical at single bond and hydroxyl radical (modified from reference 3)
Click here to view |
[Figure 1] shows the chemical structure of MK indicating its inhibitory activity against ZIKV strains from Asian and African lineages in two host cells.[3] There is a dose-dependent inhibition of infection due to ZIKV strain SZ01 (b), MR766 (c), and FLR (d) by montelukast in BHK-21 cells and inhibition of infection by ZIKV strain SZ01 (e), MR766 (f), and FLR (g) in Vero E6 cells. Curcumin from turmeric, an anti-ZIKV drug, was included as a positive control.
There is evidence that the use of MK can block infection at the early stage of virus life cycle which may be of great value in the prevention of spread of infection to other organs.[5] MK was developed for treatment of patients with asthma because of its leukotriene receptor antagonist activity.[4],[5],[6] There is only a little knowledge about its potential mechanism of the antiviral activity against ZIKV, DENV, and YFV. In an experimental study, MK was added with virus simultaneously (time 0) or at different time points after viral infection.[3] At 16 hpi, the supernatant was discarded, and the cells were then washed to perform the plaque assay for evaluating the inhibitory effects of MK at different time points. The assay of viral RNA replication confirmed that MK and NITD008 (an adenosine nucleoside inhibitor) targeting the stage of replication of flavivirus RNA were both added 4 hpi.[3] The patterns of the time of addition in the experiment and assay of viral RNA replication were similar for DENV-2 and YFV 17D, suggesting that MK may inhibit infection with flavivirus at the early stage.[6],[7] Previous studies indicated that other antiviral agents have been developed and are under evaluation for treatment of infection due to COVID-19 as well as other viral infections.[8] However, remdesivir has been found to be promising, but many patients continue to die despite therapy within agent.[2],[9],[10]
In the pandemic due to COVID-19, many infected subjects are asymptomatic or experience mild symptoms and recover without medical intervention.[1],[2] However, those with comorbid hypertension, diabetes, obesity, and heart disease as well as subjects above 50 years are at higher risk of life-threatening illness.[2] Remdesivir, a nucleotide drug with active metabolite, inhibits viral RNA dependent RNA polymerases that are structurally conserved enzymes playing a key role in the replication of a broad range of viruses, including infection with COVID 19.[2] However, it may not be better than standard therapy in many patients with moderate COVID-19.
In brief, it is possible that the addition of MK to standard treatment may have provided additional protective effects against COVID-19 spread and complications. Large randomized, controlled trials and in vitro experiments are necessary to provide a proof about its antiviral activity in COVID-19 patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | |
| 2. | Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: A randomized clinical trial. JAMA 2020;324:1048-57.  |
| 3. | Chen Y, Li Yuan, Wang X, Zou P. Montelukast, an anti-asthmatic drug, inhibits Zika virus infection by disrupting viral integrity. Front Microbiol 2020;10:3079. |
| 4. | Suddek GM. Montelukast: Much more than an antiasthma drug. Int J Basic and Clin Pharmaco 2014;3:321-28. |
| 5. | Dilek F, Ozkaya E, Kocyigit A, Yazici M, Kesgin S, Gedik AH, et al. Effect of Montelukast monotherapy on oxidative stress parameters and DNA damage in children with asthma. Int Arch Allergy Immunol 2015;167:119-26. |
| 6. | Cavero-Carbonell C, Vinkel-Hansen A, Rabanque-Hernandez MJ, Martos C, Garne E. Fetal exposure to montelukast and congenital anomalies: A population based study in Denmark. Birth Defect Res 2017;109:452-9. |
| 7. | Deng YQ, Zhang NN, Li CF, Tian M, Hao JN, Xie XP, et al. Adenosine analog NITD008 is a potent inhibitor of Zika virus. Open Forum Infect Dis 2016;3:ofw175. |
| 8. | Delvecchio R, Higa LM, Pezzuto P, Valadao AL, Garcez PP, Monteiro FL, et al. Chloroquine, an endocytosis blocking agent, inhibits Zika virus infection in different cell models. Viruses 2016;8:322. |
| 9. | Yeming Wang, Dingyu Zhang, Guanhua Du, Ronghui Du, Jianping Zhao, Yang Jin. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-78. |
| 10. | Goldman JD, Lye DC, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020;383:1827-37. |
[Figure 1]
|
Search Pubmed for