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Anti-Infective Agents

Editor-in-Chief

ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Review Article

Therapeutic uses of Antihistamines in the Management of COVID-19: A Narrative Review

Author(s): Mahshid Ataei, Omid Arasteh, Armin Salek Maghsoudi, Shokoufeh Hassani and Hesamoddin Hosseinjani*

Volume 21, Issue 2, 2023

Published on: 08 November, 2022

Article ID: e260922209160 Pages: 7

DOI: 10.2174/2211352520666220926153205

Price: $65

Abstract

Background: The first case of COVID-19 emerged in China in 2019 and spread rapidly worldwide. Therefore, all researchers worldwide sought ways to treat and prevent the disease. Since the production of vaccines and new drugs is time-consuming, a good way is to look at existing drugs to find new effects.

Objective: Due to the pathogenic mechanism of COVID-19, most of its symptoms, including anosmia, ageusia, and cytokine storm, are dependent on the release of histamine and its activities. Therefore, one category of drugs that may be effective in treating and improving the symptoms of COVID-19 is antihistamines. This paper reviewed studies that have been done so far on the effects of antihistamines, specially famotidine, in COVID-19.

Methods: A literature search was performed using scientific databases such as PubMed, Web of Science, Scopus, and Google Scholar from the beginning up to December 2021. The most relevant articles considering the potential impacts of antihistamines against COVID-19 were collected.

Results: In addition to the current medications prescribed for the treatment of SARS-CoV-2, H1 and H2 blockers are promising drugs for repurposing in the COVID-19 remedy. Several studies on famotidine were performed using virtual screening to determine whether they are effective. Many studies have shown that famotidine use improved COVID-19 symptoms and reduced the need for intubation and mortality. However, few studies concluded that famotidine is ineffective.

Conclusion: Antihistamines, and specifically famotidine, are effective in reducing COVID-19 symptoms. Therefore, they are a good choice for combination therapy with other drugs to treat COVID-19.

Keywords: Coronavirus, SARS-CoV-2, COVID-19, antihistamine, H2 blocker, famotidine.

Graphical Abstract
[1]
Velavan, T.P.; Meyer, C.G. The COVID‐19 epidemic. Trop. Med. Int. Health, 2020, 25(3), 278-280.
[http://dx.doi.org/10.1111/tmi.13383] [PMID: 32052514]
[2]
Dashraath, P.; Wong, J.L.J.; Lim, M.X.K.; Lim, L.M.; Li, S.; Biswas, A.; Choolani, M.; Mattar, C.; Su, L.L. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am. J. Obstet. Gynecol., 2020, 222(6), 521-531.
[http://dx.doi.org/10.1016/j.ajog.2020.03.021] [PMID: 32217113]
[3]
dos Santos, J.M.; Moreli, M.L.; Tewari, S.; Benite-Ribeiro, S.A. The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective. Metabolism, 2015, 64(12), 1619-1628.
[http://dx.doi.org/10.1016/j.metabol.2015.09.013] [PMID: 26481513]
[4]
Cao, Y.; Deng, Q.; Dai, S. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence. Travel Med. Infect. Dis., 2020, 35, 101647.
[http://dx.doi.org/10.1016/j.tmaid.2020.101647] [PMID: 32247927]
[5]
Sen Gupta, P.S.; Biswal, S.; Singha, D.; Rana, M.K. Binding insight of clinically oriented drug famotidine with the identified potential target of SARS-CoV-2. J. Biomol. Struct. Dyn., 2021, 39(14), 5327-5333.
[http://dx.doi.org/10.1080/07391102.2020.1784795] [PMID: 32579065]
[6]
Mather, J.F.; Seip, R.L.; McKay, R.G. Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19. Am. J. Gastroenterol., 2020, 115(10), 1617-1623.
[http://dx.doi.org/10.14309/ajg.0000000000000832] [PMID: 32852338]
[7]
Eldanasory, O.A.; Eljaaly, K.; Memish, Z.A.; Al-Tawfiq, J.A. Histamine release theory and roles of antihistamine in the treatment of cytokines storm of COVID-19. Travel Med. Infect. Dis., 2020, 37, 101874.
[http://dx.doi.org/10.1016/j.tmaid.2020.101874] [PMID: 32891724]
[8]
Raymond, M.; Ching-A-Sue, G.; Oliver, V.H. Mast cell stabilisers, leukotriene antagonists and antihistamines: A rapid review of effectiveness in COVID-19., 2020. Available from: cebm.net/covid-19/mast-cell-stabilisers-leukotriene-antagonists-and-antihistamines-a-rapid-review-of-effectiveness-in-covid-19/
[9]
Oh, K.K.; Adnan, M.; Cho, D.H. Network pharmacology study to elucidate the key targets of underlying antihistamines against COVID-19. Curr. Issues Mol. Biol., 2022, 44(4), 1597-1609.
[http://dx.doi.org/10.3390/cimb44040109] [PMID: 35723367]
[10]
Hogan, R.B., II; Hogan, R.B., III; Cannon, T.; Rappai, M.; Studdard, J.; Paul, D.; Dooley, T.P. Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm. Pharmacol. Ther., 2020, 63, 101942.
[http://dx.doi.org/10.1016/j.pupt.2020.101942] [PMID: 32871242]
[11]
Reznikov, L.R.; Norris, M.H.; Vashisht, R.; Bluhm, A.P.; Li, D.; Liao, Y.S.J.; Brown, A.; Butte, A.J.; Ostrov, D.A. Identification of antiviral antihistamines for COVID-19 repurposing. Biochem. Biophys. Res. Commun., 2021, 538, 173-179.
[http://dx.doi.org/10.1016/j.bbrc.2020.11.095] [PMID: 33309272]
[12]
COVID-19 disease leading to chronic spontaneous urticaria exacerbation: A Romanian retrospective study. Muntean, I.A.; Pintea, I.; Bocsan, I.C.; Dobrican, C.T.; Deleanu, D., Eds.; Healthcare; MDPI, 2021.
[13]
Malone, R.W.; Tisdall, P.; Fremont-Smith, P.; Liu, Y.; Huang, X.P.; White, K.M.; Miorin, L.; Moreno, E.; Alon, A.; Delaforge, E.; Hennecker, C.D.; Wang, G.; Pottel, J.; Blair, R.V.; Roy, C.J.; Smith, N.; Hall, J.M.; Tomera, K.M.; Shapiro, G.; Mittermaier, A.; Kruse, A.C.; García-Sastre, A.; Roth, B.L.; Glasspool-Malone, J.; Ricke, D.O. COVID-19: Famotidine, histamine, mast cells, and mechanisms. Front. Pharmacol., 2021, 12, 633680.
[http://dx.doi.org/10.3389/fphar.2021.633680] [PMID: 33833683]
[14]
Theoharides, T.C.; Antonopoulou, S.; Demopoulos, C.A. Coronavirus 2019, microthromboses, and platelet activating factor. Clin. Ther., 2020, 42(10), 1850-1852.
[http://dx.doi.org/10.1016/j.clinthera.2020.08.006] [PMID: 32883529]
[15]
Singh, V.P.; El-Kurdi, B.; Rood, C. What underlies the benefit of famotidine formulations used during COVID-19? Gastroenterology, 2021, 160(5), 1899-1900.
[http://dx.doi.org/10.1053/j.gastro.2020.07.051] [PMID: 32777281]
[16]
Janowitz, T.; Gablenz, E.; Pattinson, D.; Wang, T.C.; Conigliaro, J.; Tracey, K.; Tuveson, D. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: A case series. Gut, 2020, 69(9), 1592-1597.
[http://dx.doi.org/10.1136/gutjnl-2020-321852] [PMID: 32499303]
[17]
Freedberg, D.E.; Conigliaro, J.; Wang, T.C.; Tracey, K.J.; Callahan, M.V.; Abrams, J.A. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: A propensity score matched retrospective cohort study. Gastroenterology, 2020, 159(3), 1129-1131.
[http://dx.doi.org/10.1053/j.gastro.2020.05.053]
[18]
Rogosnitzky, M.; Berkowitz, E.; Jadad, A.R. Delivering benefits at speed through real-world repurposing of off-patent drugs: The COVID-19 pandemic as a case in point. JMIR Public Health Surveill., 2020, 6(2), e19199.
[http://dx.doi.org/10.2196/19199] [PMID: 32374264]
[19]
Ortega, J.T.; Serrano, M.L.; Jastrzebska, B. Class AG protein-coupled receptor antagonist famotidine as a therapeutic alternative against SARS-CoV2: An in silico analysis. Biomolecules, 2020, 10(6), 954.
[http://dx.doi.org/10.3390/biom10060954] [PMID: 32599963]
[20]
Mura, C.; Preissner, S.; Nahles, S.; Heiland, M.; Bourne, P.E.; Preissner, R. Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients. Signal Transduct. Target. Ther., 2021, 6(1), 267.
[http://dx.doi.org/10.1038/s41392-021-00689-y] [PMID: 34262013]
[21]
Panoutsopoulos, A.A. Known drugs and small molecules in the battle for COVID-19 treatment. Genes Dis., 2020, 7(4), 528-534.
[http://dx.doi.org/10.1016/j.gendis.2020.06.007] [PMID: 32837982]
[22]
Gitahy Falcao Faria, C.; Weiner, L.; Petrignet, J.; Hingray, C.; Ruiz De Pellon Santamaria, Á.; Villoutreix, B.O.; Beaune, P.; Leboyer, M.; Javelot, H. Antihistamine and cationic amphiphilic drugs, old molecules as new tools against the COVID-19? Med. Hypotheses, 2021, 148, 110508.
[http://dx.doi.org/10.1016/j.mehy.2021.110508] [PMID: 33571758]
[23]
Ge, S.; Wang, X.; Hou, Y.; Lv, Y.; Wang, C.; He, H. Repositioning of histamine H1 receptor antagonist: Doxepin inhibits viropexis of SARS-CoV-2 Spike pseudovirus by blocking ACE2. Eur. J. Pharmacol., 2021, 896, 173897.
[http://dx.doi.org/10.1016/j.ejphar.2021.173897] [PMID: 33497607]
[24]
Hou, Y.; Ge, S.; Li, X.; Wang, C.; He, H.; He, L. Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis. Chem. Biol. Interact., 2021, 338, 109420.
[http://dx.doi.org/10.1016/j.cbi.2021.109420] [PMID: 33609497]
[25]
Cheung, K.S.; Hung, I.F.N.; Leung, W.K. Association between famotidine use and COVID-19 severity in Hong Kong: A territory-wide study. Gastroenterology, 2021, 160(5), 1898-1899.
[http://dx.doi.org/10.1053/j.gastro.2020.05.098] [PMID: 32682763]
[26]
Bishara, D.; Kalafatis, C.; Taylor, D. Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents. Ther. Adv. Psychopharmacol., 2020, 10, 2045125320935306.
[http://dx.doi.org/10.1177/2045125320935306] [PMID: 32612804]
[27]
Almario, C.V.; Chey, W.D.; Spiegel, B.M.R. Increased risk of COVID-19 among users of proton pump inhibitors. Am. J. Gastroenterol., 2020, 115(10), 1707-1715.
[http://dx.doi.org/10.14309/ajg.0000000000000798]
[28]
Zhang, B.; Silverman, A.L.; Bangaru, S.; Arneson, D.; Dasharathy, S.; Nguyen, N.; Rodden, D.; Shih, J.; Butte, A.J.; El-Nachef, W.N.; Boland, B.S.; Rudrapatna, V.A. Case–control study of the association of chronic acid suppression and social determinants of health with COVID-19 infection. Sci. Rep., 2021, 11(1), 20987.
[http://dx.doi.org/10.1038/s41598-021-00367-7] [PMID: 34697319]
[29]
Sauvat, A.; Ciccosanti, F.; Colavita, F.; Di Rienzo, M.; Castilletti, C.; Capobianchi, M.R.; Kepp, O.; Zitvogel, L.; Fimia, G.M.; Piacentini, M.; Kroemer, G. On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2. Cell Death Dis., 2020, 11(8), 656.
[http://dx.doi.org/10.1038/s41419-020-02842-x] [PMID: 32814759]
[30]
Kandeel, M.; Abdelrahman, A.H.M.; Oh-Hashi, K.; Ibrahim, A.; Venugopala, K.N.; Morsy, M.A.; Ibrahim, M.A.A. Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease. J. Biomol. Struct. Dyn., 2021, 39(14), 5129-5136.
[http://dx.doi.org/10.1080/07391102.2020.1784291] [PMID: 32597315]
[31]
Fan, X.; Liu, Z.; Miyata, T.; Dasarathy, S.; Rotroff, D.M.; Wu, X. Effect of acid suppressants on the risk of COVID-19: A propensity score-matched study using UK Biobank. Gastroenterology, 2021, 160(1), 455-458.
[http://dx.doi.org/10.1053/j.gastro.2020.09.028]
[32]
Amini Pouya, M.; Afshani, S.M.; Maghsoudi, A.S.; Hassani, S.; Mirnia, K. Classification of the present pharmaceutical agents based on the possible effective mechanism on the COVID-19 infection. Daru, 2020, 28(2), 745-764.
[http://dx.doi.org/10.1007/s40199-020-00359-4] [PMID: 32734518]
[33]
Chenchula, S.; Ray, A.; Sadasivam, B. Famotidine repurposing for novel Corona virus disease of 2019: A systematic review. Drug Res. (Stuttg.), 2021, 71(6), 295-301.
[http://dx.doi.org/10.1055/a-1397-6763] [PMID: 33757133]
[34]
Sun, C.; Chen, Y.; Hu, L.; Wu, Y.; Liang, M.; Ayaz Ahmed, M.; Bhan, C.; Guo, Z.; Yang, H.; Zuo, Y.; Yan, Y.; Zhou, Q. Does famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? A systemic review and meta-analysis. Dig. Dis. Sci., 2021, 66(11), 3929-3937.
[http://dx.doi.org/10.1007/s10620-021-06872-z] [PMID: 33625613]
[35]
Akinbolade, S.; Coughlan, D.; Fairbairn, R.; McConkey, G.; Powell, H.; Ogunbayo, D.; Craig, D. Combination therapies for COVID‐19: An overview of the clinical trials landscape. Br. J. Clin. Pharmacol., 2022, 88(4), 1590-1597.
[http://dx.doi.org/10.1111/bcp.15089] [PMID: 34558094]
[36]
Spanakis, M.; Patelarou, A.; Patelarou, E.; Tzanakis, N. Drug interactions for patients with respiratory diseases receiving COVID-19 emerged treatments. Int. J. Environ. Res. Public Health, 2021, 18(21), 11711.
[http://dx.doi.org/10.3390/ijerph182111711] [PMID: 34770225]
[37]
Poddighe, D.; Kovzel, E. Impact of anti-type 2 inflammation biologic therapy on COVID-19 clinical course and outcome. J. Inflamm. Res., 2021, 14, 6845-6853.
[http://dx.doi.org/10.2147/JIR.S345665] [PMID: 34934335]
[38]
May, B.C.; Gallivan, K.H. Levocetirizine and montelukast in the COVID-19 treatment paradigm. Int. Immunopharmacol., 2022, 103, 108412.
[http://dx.doi.org/10.1016/j.intimp.2021.108412] [PMID: 34942461]
[39]
Morán, B.J.I.; Alvarenga, B.J.A.; Homma, S.; Suzuki, K.; Fremont-Smith, P.; Villar, G.H.K. Antihistamines and azithromycin as a treatment for COVID-19 on primary health care-A retrospective observational study in elderly patients. Pulm. Pharmacol. Ther., 2021, 67, 101989.
[http://dx.doi.org/10.1016/j.pupt.2021.101989] [PMID: 33465426]
[40]
Bostan, E.; Zaid, F.; Karaduman, A.; Dogan, S.; Gulseren, D.; Yalici-Armagan, B.; Akdogan, N.; Ersoy-Evans, S.; Elcin, G. The effect of COVID‐19 on patients with chronic spontaneous urticaria treated with omalizumab and antihistamines: A cross‐sectional, comparative study. J. Cosmet. Dermatol., 2021, 20(11), 3369-3375.
[http://dx.doi.org/10.1111/jocd.14484] [PMID: 34599630]

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