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ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

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Review Article

Off-label Use of Medicines in COVID-19: A Lesson For Future

Author(s): Ali Asghar Hemmati and Hoda Mojiri-Forushani*

Volume 5, Issue 1, 2024

Published on: 14 November, 2023

Article ID: e141123223568 Pages: 12

DOI: 10.2174/0126667975271719231107052426

Price: $65

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Abstract

The COVID-19 infection is rapidly spreading worldwide. Treating this new viral infection is a great challenge worldwide. There is no specific and approved medication for its treatment, so some medications are considered off-label. Antivirals, corticosteroids, antimalarial agents, and antibiotics are proposed in different countries to treat COVID-19. This narrative review discussed the off-label use of medications for COVID-19 and the beneficial and adverse effects of them. Evidence was collected and sorted from the literature ranging from 2019 to 2022 on scientific databases such as Web of Science, PubMed, and Scopus with suitable keywords. All papers, namely systematic reviews, case studies, and clinical guidelines, were evaluated. Antimalarial agents, antivirals, antibiotics, corticosteroids, NSAIDs, biological medicines, Ivermectin, and melatonin were reviewed in this study. Some medications have direct antiviral effects, and many can reduce infection symptoms and hospitalization. In some clinical trial trials, even some of them, such as corticosteroids, can lower death rates, particularly during the cytokine storm period. However, the effectiveness of some medications has not been understood. Besides, the side effects of off-label use of these medications must be considered a serious concern. There are no proven medications for COVID-19 yet. Off-label use of medications is a double-edged sword that can have advantages outweighing its disadvantages. The COVID-19 crisis taught us many lessons about dealing with health-related crises and their treatment management. One of the most important lessons is paying more attention to the discovery and development of novel drugs and vaccines based on modern technology.

Graphical Abstract

[1]
Perlman S. Another decade, another coronavirus. N Engl J Med 2020; 382(8): 760-2.
[2]
Ghebreyesus T. WHO Director-General’s opening remarks at the media briefing on COVID-19-25. World Health Organization 2020.
[3]
Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[4]
Kim SY, Yeniova AÖ. Global, regional, and national incidence and mortality of COVID-19 in 237 countries and territories, January 2022: A systematic analysis for World Health Organization COVID-19 Dashboard Life Cycle 2022; 2: e10.
[5]
Torres C, García J, Meslé F, et al. Identifying age- and sex-specific COVID-19 mortality trends over time in six countries. Int J Infect Dis 2023; 128: 32-40.
[http://dx.doi.org/10.1016/j.ijid.2022.12.004] [PMID: 36509336]
[6]
Jia Z, Song X, Shi J, Wang W, He K. Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19). Pathog Dis 2020; 78(4): ftaa036.
[http://dx.doi.org/10.1093/femspd/ftaa036] [PMID: 32667665]
[7]
Asai A, Konno M, Ozaki M, et al. COVID-19 drug discovery using intensive approaches. Int J Mol Sci 2020; 21(8): 2839.
[http://dx.doi.org/10.3390/ijms21082839] [PMID: 32325767]
[8]
Zhong LLD, Lam WC, Yang W, et al. Potential targets for treatment of coronavirus disease 2019 (COVID-19): a review of Qing-Fei-Pai-Du-Tang and its major herbs. Am J Chin Med 2020; 48(5): 1051-71.
[http://dx.doi.org/10.1142/S0192415X20500512] [PMID: 32668969]
[9]
Information for clinicians on therapeutic options for COVID-19 patients. 2019. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-optionshtml (Accessed on: April. 2020; 2).
[10]
FitzGerald GA. Misguided drug advice for COVID-19. Science 2020; 367(6485): 1434.
[http://dx.doi.org/10.1126/science.abb8034] [PMID: 32198292]
[11]
Hempelmann E. Hemozoin Biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors. Parasitol Res 2007; 100(4): 671-6.
[http://dx.doi.org/10.1007/s00436-006-0313-x] [PMID: 17111179]
[12]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2(1): 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[13]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[14]
Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: Pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol 2020; 39(7): 2085-94.
[http://dx.doi.org/10.1007/s10067-020-05190-5] [PMID: 32474885]
[15]
Yao X, Ye F, Zhang M, et al. in vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; 71(15): 732-9.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[16]
Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 2020; 2020: 369.
[17]
Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020; 382(25): 2411-8.
[http://dx.doi.org/10.1056/NEJMoa2012410] [PMID: 32379955]
[18]
Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis 2020; 34: 101663.
[http://dx.doi.org/10.1016/j.tmaid.2020.101663] [PMID: 32289548]
[19]
Molina JM, Delaugerre C, Le Goff J, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect 2020; 50(4): 384.
[http://dx.doi.org/10.1016/j.medmal.2020.03.006] [PMID: 32240719]
[20]
Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nat Med 2020; 26(6): 808-9.
[http://dx.doi.org/10.1038/s41591-020-0888-2] [PMID: 32488217]
[21]
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56(1): 105949.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[22]
Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med 2020; 383(6): 517-25.
[http://dx.doi.org/10.1056/NEJMoa2016638] [PMID: 32492293]
[23]
Hu M, Zheng X, Fan C-M, Zheng Y. Chloroquine Hype Derails Coronavirus Drug Trials. Ledford, Heidi. Nature: London 2020; 580.
[24]
Moore N. Chloroquine for COVID-19 infection. Drug Saf 2020; 43(5): 393-4.
[http://dx.doi.org/10.1007/s40264-020-00933-4] [PMID: 32266694]
[25]
Yazdany J, Kim AHJ. Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: What every clinician should know. Ann Intern Med 2020; 172(11): 754-5.
[http://dx.doi.org/10.7326/M20-1334] [PMID: 32232419]
[26]
Horby P, Mafham M, Linsell L, Bell J, Staplin N, Emberson J. Effect of hydroxychloroquine in hospitalized patients with COVID-19: Preliminary results from a multi-center, randomized, controlled trial. MedRxiv 2020.2020.
[http://dx.doi.org/10.1101/2020.07.15.20151852]
[27]
Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): A multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet 2014; 383(9922): 1049-58.
[http://dx.doi.org/10.1016/S0140-6736(13)62568-4] [PMID: 24360369]
[28]
Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol 2006; 44(2): 173-5.
[http://dx.doi.org/10.1080/15563650500514558] [PMID: 16615675]
[29]
Stas P, Faes D, Noyens P. Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. Int J Cardiol 2008; 127(2): e80-2.
[http://dx.doi.org/10.1016/j.ijcard.2007.04.055] [PMID: 17590456]
[30]
Szekely Y, Lichter Y, Shrkihe BA, Bruck H, Oster HS, Viskin S. Chloroquine-induced torsades de pointes in a patient with coronavirus disease 2019. Heart Rhythm 2020; 17(9): 1452-5.
[http://dx.doi.org/10.1016/j.hrthm.2020.04.046] [PMID: 32380291]
[31]
Riou B, Barriot P, Rimailho A, Baud FJ. Treatment of severe chloroquine poisoning. N Engl J Med 1988; 318(1): 1-6.
[http://dx.doi.org/10.1056/NEJM198801073180101] [PMID: 3336379]
[32]
Chary MA, Barbuto AF, Izadmehr S, Hayes BD, Burns MM. COVID-19: Therapeutics and their toxicities. J Med Toxicol 2020; 16(3): 284-94.
[http://dx.doi.org/10.1007/s13181-020-00777-5] [PMID: 32356252]
[33]
Somer M, Kallio J, Pesonen U, Pyykkö K, Huupponen R, Scheinin M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol 2000; 49(6): 549-54.
[http://dx.doi.org/10.1046/j.1365-2125.2000.00197.x] [PMID: 10848718]
[34]
Ling NWA, Tsz FCI, Graham CA. Hydroxychloroquine overdose: Case report and recommendations for management. Eur J Emerg Med 2008; 15(1): 16-8.
[http://dx.doi.org/10.1097/MEJ.0b013e3280adcb56] [PMID: 18180661]
[35]
Naksuk N, Lazar S, Peeraphatdit TB. Cardiac safety of off-label COVID-19 drug therapy: A review and proposed monitoring protocol. Eur Heart J Acute Cardiovasc Care 2020; 9(3): 215-21.
[http://dx.doi.org/10.1177/2048872620922784] [PMID: 32372695]
[36]
Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5(9): 1036-41.
[http://dx.doi.org/10.1001/jamacardio.2020.1834] [PMID: 32936252]
[37]
Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ 2020; 192(17): E450-3.
[http://dx.doi.org/10.1503/cmaj.200528] [PMID: 32269021]
[38]
Wu CI, Postema PG, Arbelo E, et al. SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes. Heart Rhythm 2020; 17(9): 1456-62.
[http://dx.doi.org/10.1016/j.hrthm.2020.03.024] [PMID: 32244059]
[39]
Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res 2020; 7(1): 11.
[http://dx.doi.org/10.1186/s40779-020-00240-0]
[40]
Gillenwater S, Rahaghi F, Hadeh A. Remdesivir for the treatment of COVID-19-preliminary report. N Engl J Med 2020; 383(10): 992-4.
[http://dx.doi.org/10.1056/NEJMc2022236] [PMID: 32649074]
[41]
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395(10236): 1569-78.
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9] [PMID: 32423584]
[42]
Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020; 383(19): 1827-37.
[http://dx.doi.org/10.1056/NEJMoa2015301] [PMID: 32459919]
[43]
Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, et al. Emerging treatment strategies for COVID-19 infection. Clin Exp Med 2021; 21(2): 167-79.
[http://dx.doi.org/10.1007/s10238-020-00671-y] [PMID: 33128197]
[44]
Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med 2022; 386(4): 305-15.
[http://dx.doi.org/10.1056/NEJMoa2116846] [PMID: 34937145]
[45]
Ali K, Azher T, Baqi M, et al. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: A randomized controlled trial. CMAJ 2022; 194(7): E242-51.
[http://dx.doi.org/10.1503/cmaj.211698] [PMID: 35045989]
[46]
Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med 2020; 382(24): 2327-36.
[http://dx.doi.org/10.1056/NEJMoa2007016] [PMID: 32275812]
[47]
Udwadia ZF, Singh P, Barkate H, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis 2021; 103: 62-71.
[http://dx.doi.org/10.1016/j.ijid.2020.11.142] [PMID: 33212256]
[48]
Sirijatuphat R, Manosuthi W, Niyomnaitham S, et al. Early treatment of Favipiravir in COVID-19 patients without pneumonia: A multicentre, open-labelled, randomized control study. Emerg Microbes Infect 2022; 11(1): 2197-206.
[http://dx.doi.org/10.1080/22221751.2022.2117092] [PMID: 35997325]
[49]
Shah PL, Orton CM, Grinsztejn B, et al. Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): A multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care. Lancet Respir Med 2023; 11(5): 415-24.
[http://dx.doi.org/10.1016/S2213-2600(22)00412-X] [PMID: 36528039]
[50]
Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med 2020; 38(7): 1488-93.
[http://dx.doi.org/10.1016/j.ajem.2020.04.035] [PMID: 32336586]
[51]
Chu CM, Cheng VC, Hung IF, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax 2004; 59(3): 252-6.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[52]
Park SY, Lee JS, Son JS, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect 2019; 101(1): 42-6.
[http://dx.doi.org/10.1016/j.jhin.2018.09.005] [PMID: 30240813]
[53]
Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020; 382(19): 1787-99.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[54]
Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y. Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: An exploratory randomized controlled trial. Med 2020; 1(1): 105-13.e4.
[55]
Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: The application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci 2020; 35(6): e79.
[56]
Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 2020; 14(1): 64-8.
[http://dx.doi.org/10.5582/bst.2020.01030] [PMID: 32037389]
[57]
Rock BM, Hengel SM, Rock DA, Wienkers LC, Kunze KL. Characterization of ritonavir-mediated inactivation of cytochrome P450 3A4. Mol Pharmacol 2014; 86(6): 665-74.
[http://dx.doi.org/10.1124/mol.114.094862] [PMID: 25274602]
[58]
Grayson ML, Cosgrove SE, Crowe S, Hope W, McCarthy JS, Mills J. Kucers’ The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, -Three Volume Set. CRC Press 2017.
[59]
Garzel B, Yang H, Zhang L, Huang SM, Polli JE, Wang H. The role of bile salt export pump gene repression in drug-induced cholestatic liver toxicity. Drug Metab Dispos 2014; 42(3): 318-22.
[http://dx.doi.org/10.1124/dmd.113.054189] [PMID: 24335466]
[60]
Giwa A, Desai A. Novel coronavirus COVID-19: An overview for emergency clinicians. Emerg Med Pract 2020; 22(S2): 1-21.
[PMID: 31978294]
[61]
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci 2020; 117(20): 10970-5.
[http://dx.doi.org/10.1073/pnas.2005615117] [PMID: 32350134]
[62]
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020; 55(5): 105954.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105954] [PMID: 32234467]
[63]
Gritti G, Raimondi F, Ripamonti D, Riva I, Landi F, Alborghetti L. IL-6 signalling pathway inactivation with siltuximab in patients with COVID-19 respiratory failure: An observational cohort study. Medrxiv 2020; 2020.04.
[http://dx.doi.org/10.1101/2020.04.01.20048561]
[64]
Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis 2021; 73(2): e445-54.
[http://dx.doi.org/10.1093/cid/ciaa954] [PMID: 32651997]
[65]
Felton T, Murray C, Evans D, Dark P, Buch M. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2021; 397(10285): 1637-45.
[http://dx.doi.org/10.1016/S0140-6736(21)00676-0] [PMID: 33933206]
[66]
Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med 2020; 46(5): 854-87.
[http://dx.doi.org/10.1007/s00134-020-06022-5] [PMID: 32222812]
[67]
Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382(18): 1708-20.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[68]
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020; 8(4): e21.
[http://dx.doi.org/10.1016/S2213-2600(20)30116-8] [PMID: 32171062]
[69]
Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581(7807): 221-4.
[http://dx.doi.org/10.1038/s41586-020-2179-y] [PMID: 32225175]
[70]
Abani O, Abbas A, Abbas F, et al. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2022; 399(10320): 143-51.
[http://dx.doi.org/10.1016/S0140-6736(21)01825-0] [PMID: 34800427]
[71]
Ravichandran R, Mohan SK, Sukumaran SK, Kamaraj D, Daivasuga SS, Ravi SOAS. An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients. Sci Rep 2022; 12(1): 1-10.
[PMID: 34992227]
[72]
Asadi M, Sayar S, Radmanesh E, et al. Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized, double-blind, placebo-controlled, clinical trial. Diabetes Metab Syndr 2021; 15(6): 102319.
[http://dx.doi.org/10.1016/j.dsx.2021.102319] [PMID: 34700294]
[73]
Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal. J Heart Lung Transplant 2020; 39(5): 405-7.
[http://dx.doi.org/10.1016/j.healun.2020.03.012] [PMID: 32362390]
[74]
Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020; 395(10225): 683-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30361-5] [PMID: 32122468]
[75]
Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med 2018; 197(6): 757-67.
[http://dx.doi.org/10.1164/rccm.201706-1172OC] [PMID: 29161116]
[76]
Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 2004; 31(4): 304-9.
[http://dx.doi.org/10.1016/j.jcv.2004.07.006] [PMID: 15494274]
[77]
Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as adjunctive therapy in the treatment of influenza: An updated Cochrane systematic review and meta-analysis. Crit Care Med 2020; 48(2): e98-e106.
[http://dx.doi.org/10.1097/CCM.0000000000004093] [PMID: 31939808]
[78]
Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial. Lancet Respir Med 2020; 8(3): 267-76.
[http://dx.doi.org/10.1016/S2213-2600(19)30417-5] [PMID: 32043986]
[79]
Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020; 180(7): 934-43.
[http://dx.doi.org/10.1001/jamainternmed.2020.0994] [PMID: 32167524]
[80]
Fernández Cruz A, Ruiz-Antorán B, Gómez AM, Sancho López A, Sánchez PM, Soto GAC. Impact of glucocorticoid treatment in SARS-CoV-2 infection mortality: A retrospective controlled cohort study. medRxiv 2020; 2020.05.
[http://dx.doi.org/10.1101/2020.05.22.20110544]
[81]
Chappell L, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL. Dexamethasone in hospitalized patients with COVID-19-preliminary report. N Engl J Med 2021; 384(8): 693-704.
[82]
Granholm A, Munch MW, Myatra SN, et al. Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: A pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial. Intensive Care Med 2022; 48(1): 45-55.
[http://dx.doi.org/10.1007/s00134-021-06573-1] [PMID: 34757439]
[83]
Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. World Health Organization 2020.
[84]
Stockman LJ, Bellamy R, Garner P. SARS: Systematic review of treatment effects. PLoS Med 2006; 3(9): e343.
[http://dx.doi.org/10.1371/journal.pmed.0030343] [PMID: 16968120]
[85]
Crump A, Ōmura S. Ivermectin, ‘Wonder drug’ from Japan: The human use perspective. Proc Jpn Acad, Ser B, Phys Biol Sci 2011; 87(2): 13-28.
[http://dx.doi.org/10.2183/pjab.87.13] [PMID: 21321478]
[86]
Kircik LH, Del Rosso JQ, Layton AM, Schauber J. Over 25 years of clinical experience with ivermectin: An overview of safety for an increasing number of indications. J Drugs Dermatol 2016; 15(3): 325-32.
[PMID: 26954318]
[87]
Chaccour C, Casellas A, Blanco-Di Matteo A, et al. The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial. EClinicalMedicine 2021; 32: 100720.
[http://dx.doi.org/10.1016/j.eclinm.2020.100720] [PMID: 33495752]
[88]
Elgazzar A, Eltaweel A, Youssef SA, Hany B, Hafez M, Moussa H. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Res Sq 2020.
[89]
López-Medina E, López P, Hurtado IC, et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: A randomized clinical trial. JAMA 2021; 325(14): 1426-35.
[http://dx.doi.org/10.1001/jama.2021.3071] [PMID: 33662102]
[90]
Ahmed S, Karim MM, Ross AG, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis 2021; 103: 214-6.
[http://dx.doi.org/10.1016/j.ijid.2020.11.191] [PMID: 33278625]
[91]
Chahla RE, Medina Ruiz L, Ortega ES, Morales MF, Barreiro F, George A. A randomized trial-intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents. MedRxiv 2021; 2021.03.
[http://dx.doi.org/10.1101/2021.03.26.21254398]
[92]
Shouman WM, Hegazy AA, Nafae RM, Ragab MI, Samra SR, Ibrahim DA. Use of ivermectin as a potential chemoprophylaxis for COVID-19 in Egypt: A randomized clinical trial. J Clin Diagn Res 2021; 15(2): 10.7860.
[93]
Hashim HA, Maulood MF, Rasheed AM, Fatak DF, Kabah KK, Abdulamir AS. Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq. MedRxiv 2020; 2020.10.
[http://dx.doi.org/10.1101/2020.10.26.20219345]
[94]
Mahmud R, Rahman MM, Alam I, et al. Ivermectin in combination with doxycycline for treating COVID-19 symptoms: A randomized trial. J Int Med Res 2021; 49(5)
[http://dx.doi.org/10.1177/03000605211013550] [PMID: 33983065]
[95]
Gheibi N, Shakhsi Niaee M, Namdar P, et al. Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial. Asian Pac J Trop Med 2021; 14(6): 266-73.
[http://dx.doi.org/10.4103/1995-7645.318304]
[96]
Okumuş N, Demirtürk N, Çetinkaya RA, et al. Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients. BMC Infect Dis 2021; 21(1): 411.
[http://dx.doi.org/10.1186/s12879-021-06104-9] [PMID: 33947344]
[97]
Ravikirti RR, Pattadar C, Raj R, Agarwal N, Biswas B. Ivermectin as a potential treatment for mild to moderate COVID-19–a double blind randomized placebo-controlled trial. MedRxiv 2021; 2021.01.
[98]
Cruciani M, Pati I, Masiello F, Malena M, Pupella S, De Angelis V. Ivermectin for prophylaxis and treatment of COVID-19: a systematic review and meta-analysis. Diagnostics 2021; 11(9): 1645.
[http://dx.doi.org/10.3390/diagnostics11091645] [PMID: 34573986]
[99]
Padhy BM, Mohanty RR, Das S, Meher BR. Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis. J Pharm Pharm Sci 2020; 23: 462-9.
[http://dx.doi.org/10.18433/jpps31457] [PMID: 33227231]
[100]
Temple C, Hoang R, Hendrickson RG. Toxic effects from ivermectin use associated with prevention and treatment of COVID-19. N Engl J Med 2021; 385(23): 2197-8.
[http://dx.doi.org/10.1056/NEJMc2114907] [PMID: 34670041]
[101]
Reiter RJ, Ma Q, Sharma R. Treatment of ebola and other infectious diseases: melatonin “goes viral”. Melatonin Research 2020; 3(1): 43-57.
[http://dx.doi.org/10.32794/mr11250047]
[102]
Boga JA, Coto-Montes A, Rosales-Corral SA, Tan DX, Reiter RJ. Beneficial actions of melatonin in the management of viral infections: A new use for this “molecular handyman”? Rev Med Virol 2012; 22(5): 323-38.
[http://dx.doi.org/10.1002/rmv.1714] [PMID: 22511571]
[103]
Anderson G, Maes M, Markus RP, Rodriguez M. Ebola virus: Melatonin as a readily available treatment option. J Med Virol 2015; 87(4): 537-43.
[http://dx.doi.org/10.1002/jmv.24130] [PMID: 25611054]
[104]
Reiter RJ, Ma Q, Sharma R. Melatonin in mitochondria: Mitigating clear and present dangers. Physiology 2020; 35(2): 86-95.
[http://dx.doi.org/10.1152/physiol.00034.2019] [PMID: 32024428]
[105]
Huang SH, Cao XJ, Liu W, Shi XY, Wei W. Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J Pineal Res 2010; 48(2): 109-16.
[http://dx.doi.org/10.1111/j.1600-079X.2009.00733.x] [PMID: 20070490]
[106]
Yip HK, Chang YC, Wallace CG, et al. Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury. J Pineal Res 2013; 54(2): 207-21.
[http://dx.doi.org/10.1111/jpi.12020] [PMID: 23110436]
[107]
Wu X, Ji H, Wang Y, Gu C, Gu W, Hu L. Melatonin alleviates radiation-induced lung injury via regulation of miR-30e/NLRP3 axis. Oxid Med Cell Longev 2019; 2019: 4087298.
[108]
Bahrampour Juybari K, Pourhanifeh MH, Hosseinzadeh A, Hemati K, Mehrzadi S. Melatonin potentials against viral infections including COVID-19: Current evidence and new findings. Virus Res 2020; 287: 198108.
[http://dx.doi.org/10.1016/j.virusres.2020.198108] [PMID: 32768490]
[109]
Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci 2020; 250: 117583.
[http://dx.doi.org/10.1016/j.lfs.2020.117583] [PMID: 32217117]
[110]
Mistraletti G, Sabbatini G, Taverna M, et al. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res 2010; 48(2): 142-7.
[http://dx.doi.org/10.1111/j.1600-079X.2009.00737.x] [PMID: 20070489]
[111]
Mistraletti G, Umbrello M, Sabbatini G, et al. Melatonin reduces the need for sedation in ICU patients: A randomized controlled trial. Minerva Anestesiol 2015; 81(12): 1298-310.
[PMID: 25969139]
[112]
van Bergen L. A new Spanish enemy; the Spanish flu in the Netherlands in the period 1918-1920 Ned Tijdschr Geneeskd 2020; 164: D5224.
[113]
Lin X, Li X, Lin X. A review on applications of computational methods in drug screening and design. Molecules 2020; 25(6): 1375.
[http://dx.doi.org/10.3390/molecules25061375] [PMID: 32197324]
[114]
Gurung AB, Ali MA, Lee J, Farah MA, Al-Anazi KM. An updated review of computer-aided drug design and its application to COVID-19. BioMed Res Int 2021 2021.
[115]
Abdellatiif MH, Ali A, Ali A, Hussien MA. Computational studies by molecular docking of some antiviral drugs with COVID-19 receptors are an approach to medication for COVID-19. Open Chem 2021; 19(1): 245-64.
[http://dx.doi.org/10.1515/chem-2021-0024]
[116]
Słońska A, Cymerys J, Skwarska J, Golke A, Bańbura MW. Influence of importin α/β and exportin 1 on equine herpesvirus type 1 (EHV-1) replication in primary murine neurons. Pol J Vet Sci 2013; 16(4): 749-51.
[http://dx.doi.org/10.2478/pjvs-2013-0106] [PMID: 24597312]

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