Comprehensive analysis of gastrointestinal side effects in COVID-19 patients undergoing combined pharmacological treatment with azithromycin and hydroxychloroquine: a systematic review and network meta-analysis

References

• Axfors C, Schmitt A, Janiaud P, Hooft JV, Abd-Elsalam S, Abdo EF, Abella BS, Akram J, Amaravadi RK, Angus DC, et al. 2021. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun. 12(1):2349. doi: 10.1038/s41467-021-22446-z.
   PubMed Web of Science ®Google Scholar
• Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, et al. 2020. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 382(19):1787–1799. doi: 10.1056/NEJMoa2001282.
   PubMed Web of Science ®Google Scholar
• Cavalcanti A, Zampieri F, Rosa R, Azevedo LCP, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Thiago Lisboa T, et al. 2020. Hydroxychloroquine with or without azithromycin in mild-to-moderate COVID-19. N Engl J Med. 383(21):2041–2052. doi: 10.1056/NEJMoa2019014.
   PubMed Web of Science ®Google Scholar
• Chaimani A, Higgins J, Mavridis D, Spyridonos P, Salanti G. 2013. Graphical tools for network meta-analysis in STATA. PLoS One. 8(10):e76654. doi: 10.1371/journal.pone.0076654.
   PubMed Web of Science ®Google Scholar
• Choudhury A, Tariq R, Jena A, Vesely EK, Singh S, Khanna S, Sharma V. 2022. Gastrointestinal manifestations of long COVID: a systematic review and meta-analysis. Therap Adv Gastroenterol. 15:17562848221118403. doi: 10.1177/17562848221118403.
   Web of Science ®Google Scholar
• DerSimonian R, Laird N. 1986. Meta-analysis in clinical trials. Control Clin Trials. 7(3):177–188. doi: 10.1016/0197-2456(86)90046-2.
   PubMedGoogle Scholar
• Doyno C, Sobieraj D, Baker W. 2021. Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose. Clin Toxicol (Phila). 59(1):12–23. doi: 10.1080/15563650.2020.1817479.
   PubMed Web of Science ®Google Scholar
• Elsawah HK, Elsokary MA, Elrazzaz MG, Elshafie AH. 2020. Hydroxychloroquine for treatment of nonsevere COVID‐19 patients: systematic review and meta‐analysis of controlled clinical trials. J Med Virol. 93(3):1265–1275. doi: 10.1002/jmv.26442.
   PubMed Web of Science ®Google Scholar
• Fallani E, Cevenini F, Lazzerini P, Verdini A, Saponara S. 2022. Off‐label use of hydroxychloroquine in COVID‐19: analysis of reports of suspected adverse reactions from the Italian national network of pharmacovigilance. J Clin Pharmacol. 62(5):646–655. doi: 10.1002/jcph.2006.
   PubMed Web of Science ®Google Scholar
• Fernández-De-Las-Peñas C, Torres-Macho J, Guijarro C, Martín-Guerrero JD, Pellicer-Valero OJ, Plaza-Manzano G. 2023. Trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors: the long COVID experience multicenter study. Viruses. 15(5):1134. doi: 10.3390/v15051134.
   PubMed Web of Science ®Google Scholar
• Galan LEB, Dos Santos NM, Asato MS, Araújo JV, Moreira AL, Araújo AMM, Paiva ADP, Portella DGS, Marques FSS, Silva GMA, et al. 2021. Phase 2 randomized study on chloroquine, hydroxychloroquine, or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection. Pathog Glob Health. 115(4):235–242. doi: 10.1080/20477724.2021.1890887.
   PubMed Web of Science ®Google Scholar
• Gavriatopoulou M, Ntanasis-Stathopoulos I, Korompoki E, Fotiou D, Migkou M, Tzanninis IG, Psaltopoulou T, Kastritis E, Terpos E, Dimopoulos MA. 2021. Emerging treatment strategies for COVID-19 infection. Clin Exp Med. 21(2):167–179. doi: 10.1007/s10238-020-00671-y.
   PubMed Web of Science ®Google Scholar
• Gevers S, Kwa MSG, Wijnans E, van Nieuwkoop C. 2020. Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clin Microbiol Infect. 26(9):1276–1277. doi: 10.1016/j.cmi.2020.05.006.
   PubMed Web of Science ®Google Scholar
• Ghanei M, Solaymani-Dodaran M, Qazvini A, Ghazale AH, Setarehdan SA, Saadat SH, Ghobadi H, Hoseininia S, Elahikhah M, Samadi AH, et al. 2021. The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial. Respir Res. 22(1):245.,. doi: 10.1186/s12931-021-01833-6.
   PubMed Web of Science ®Google Scholar
• Ghazy RM, Almaghraby A, Shaaban R, Kamal A, Beshir H, Moursi A, Ramadan A, Taha SHN. 2020. A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment. Sci Rep. 10(1):22139. doi: 10.1038/s41598-020-77748-x.
   PubMed Web of Science ®Google Scholar
• Gonzalez JL, González Gámez M, Mendoza Enciso EA, Esparza Maldonado RJ, Hernández Palacios D, Dueñas Campos S, Robles IO, Macías Guzmán MJ, García Díaz AL, Gutiérrez Peña CM, et al. 2022. Efficacy and safety of ivermectin and hydroxychloroquine in patients with severe COVID-19: a randomized controlled trial. Infect Dis Rep. 14(2):160–168. doi: 10.3390/idr14020020.
   PubMed Web of Science ®Google Scholar
• Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, Franceschini E, Cuomo G, Orlando G, Borghi V, et al. 2020. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2(8):e474–e484. doi: 10.1016/S2665-9913(20)30173-9.
   PubMedGoogle Scholar
• Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ. 2008. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 336(7650):924–926. doi: 10.1136/bmj.39489.470347.AD.
   PubMed Web of Science ®Google Scholar
• Hache G, Rolain J, Gautret P, Deharo JC, Brouqui P, Raoult D, Honoré S. 2021. Combination of hydroxychloroquine plus azithromycin as potential treatment for COVID-19 patients: safety profile, drug interactions, and management of toxicity. Microb Drug Resist. 27(3):281–290. doi: 10.1089/mdr.2020.0232.
   PubMed Web of Science ®Google Scholar
• Hentschke-Lopes M, Botton M, Borges P, Freitas M, Mancuso ACB, Matte U. 2022. Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency. Cad Saude Publica. 38(7):e00001022. doi: 10.1590/0102-311XEN001022.
   PubMed Web of Science ®Google Scholar
• Johnston C, Brown E, Stewart J, Karita HCS, Kissinger PJ, Dwyer J, Hosek S, Oyedele T, Paasche-Orlow MK, Paolino K, et al. 2021. Hydroxychloroquine with or Without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: a randomized clinical trial. EClinicalMedicine. 33:100773. doi: 10.1016/j.eclinm.2021.100773.
   PubMedGoogle Scholar
• Lamback E, Oliveira M, Haddad A, Vieira AFM, Neto ALF, Maia TS, Chrisman JR, Spineti PPM, Mattos MA, Costa E. 2021. Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19. Braz J Infect Dis. 25(2):101549. doi: 10.1016/j.bjid.2021.101549.
   PubMed Web of Science ®Google Scholar
• Landis R, Koch G. 1977. The measurement of observer agreement for categorical data. Biometrics. 33(1):159–174. doi: 10.2307/2529310.
   PubMed Web of Science ®Google Scholar
• Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, Villapol S. 2021. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 11(1):16144. doi: 10.1038/s41598-021-95565-8.
   PubMed Web of Science ®Google Scholar
• Ma S, Xu C, Liu S, Sun X, Li R, Mao M, Feng S, Wang X. 2021. Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. Signal Transduct Target Ther. 6(1):83. doi: 10.1038/s41392-021-00521-7.
   PubMed Web of Science ®Google Scholar
• Marasco G, Cremon C, Barbaro MR, Cacciari G, Falangone F, Kagramanova A, Bordin D, Drug V, Miftode E, Fusaroli P, et al. 2023. Post COVID-19 irritable bowel syndrome. Gut. 72(3):484–492. doi: 10.1136/gutjnl-2022-328483.
   Web of Science ®Google Scholar
• Million M, Lagier J, Gautret P, Colson P, Fournier PE, Amrane S, Hocquart M, Mailhe M, Esteves-Vieira V, Doudier B, et al. 2020. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis. 35:101738. doi: 10.1016/j.tmaid.2020.101738.
   PubMed Web of Science ®Google Scholar
• Moore N, Bosco-Levy P, Thurin N, Blin P, Droz-Perroteau C. 2021. NSAIDs and COVID-19: a systematic review and meta-analysis. Drug Saf. 44(9):929–938. doi: 10.1007/s40264-021-01089-5.
   PubMed Web of Science ®Google Scholar
• Moraes VY, Marra AR, Matos LL, Neto AS, Rizzo LV, Neto MC, Lenza M. 2022. Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. Einstein (Sao Paulo). 20:eRW0045. doi: 10.31744/einstein_journal/2022RW0045.
   PubMed Web of Science ®Google Scholar
• Morsali M, Doosti-Irani A, Amini S, Nazemipour M, Mansournia MA, Aliannejad R. 2023. Comparison of corticosteroids types, dexamethasone, and methylprednisolone in patients hospitalized with COVID-19: a systematic review and network meta-analysis. Glob Epidemiol. 6:100116. doi: 10.1016/j.gloepi.2023.100116.
   PubMedGoogle Scholar
• Oldenburg C, Pinsky B, Brogdon J, Chen C, Ruder K, Zhong L, Nyatigo F, Cook CA, Hinterwirth A, Lebas E, et al. 2021. Effect of oral azithromycin vs placebo on COVID-19 symptoms in outpatients with SARS-CoV-2 infection: a randomized clinical trial. JAMA. 326(6):490–498. doi: 10.1001/jama.2021.11517.
   PubMed Web of Science ®Google Scholar
• Padmaprakash K, Thareja S, Raman N, Muthukrishnan J, Miglani A, Summi P, Reddy SN. 2023. Gastrointestinal manifestations in symptomatic Coronavirus disease-19 patients and its relevance in predicting severity and outcome. Indian J Gastroenterol. 42(4):485–495. doi: 10.1007/s12664-023-01370-8.
   PubMed Web of Science ®Google Scholar
• Pitre T, Su J, Cui S, Scanlan R, Chiang C, Husnudinov R, Khalid MF, Khan N, Leung G, Mikhail D, et al. 2022. Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis. Eur Respir Rev. 31(165):220036. doi: 10.1183/16000617.0036-2022.
   PubMed Web of Science ®Google Scholar
• Puhan MA, Schünemann HJ, Murad MH, Li T, Brignardello-Petersen R, Singh JA, Kessels AG, Guyatt GH. 2014. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ. 349(sep24 5):g5630–g5630. doi: 10.1136/bmj.g5630.
   PubMed Web of Science ®Google Scholar
• Purwati BE, Miatmoko A, Lardo S, Purnama YI, Laely M, Rochmad I, Ismail T, Wulandari S, Setyawan D, Rosyid AN, Setiawan HW. 2021. A randomized, double-blind, multicenter clinical study comparing the efficacy and safety of a drug combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine for patients diagnosed with mild to moderate COVID-19 infections. Biochem Res Int. 12:6685921. doi: 10.1155/2021/6685921.
   Google Scholar
• Recovery Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, et al. 2020. Dexamethasone in hospitalized patients with Covid-19-preliminary report. N Engl J Med. 384(8):693–704. doi: 10.1056/NEJMoa2021436.
   PubMed Web of Science ®Google Scholar
• Rodrigues C, Freitas-Santos R, Levi J, Senerchia AA, Lopes ATA, Santos SR, Siciliano RF, Pierrotti LC. 2021. Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance. Int J Antimicrob Agents. 58(5):106428. doi: 10.1016/j.ijantimicag.2021.106428.
   PubMed Web of Science ®Google Scholar
• Sadeghirad B, Siemieniuk R, Brignardello-Petersen R, Papola D, Lytvyn L, Vandvik PO, Merglen A, Guyatt GH, Agoritsas T. 2017. Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomized trials. BMJ. 358:j3887. doi: 10.1136/bmj.j3887.
   PubMedGoogle Scholar
• Shamshirian A, Hessami A, Heydari K, Alizadeh-Navaei R, Ebrahimzadeh MA, Yip GW, Ghasemian R, Sedaghat M, Baradaran H, Yazdi SM, et al. 2020. The role of hydroxychloroquine in COVID-19 treatment: a systematic review and meta-analysis. Ann Acad Med Singap. 49(10):789–800. doi: 10.47102/annals-acadmedsg.2020370.
   PubMed Web of Science ®Google Scholar
• Shim S, Yoon BH, Shin IS, Bae JM. 2017. Network meta-analysis: application and practice using Stata. Epidemiol Health. 39:e2017047. doi: 10.4178/epih.e2017047.
   PubMed Web of Science ®Google Scholar
• Shimizu K, Hirata H, Kabata D, Tokuhira N, Koide M, Ueda A, Tachino J, Shintani A, Uchiyama A, Fujino Y, et al. 2022. Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: a propensity score analysis. J Infect Chemother. 28(4):548–553. doi: 10.1016/j.jiac.2021.12.024.
   PubMed Web of Science ®Google Scholar
• Sié A, Dah C, Bountogo M, Ouattara M, Nebie E, Coulibaly B, Brogdon JM, Godwin WW, Lebas E, Doan T, et al. 2020. Adverse events and clinic visits following a single dose of oral azithromycin among preschool children: a randomized placebo-controlled trial. Am J Trop Med Hyg. 104(3):1137–1141. doi: 10.4269/ajtmh.20-1002.
   PubMed Web of Science ®Google Scholar
• Sivapalan P, Ulrik C, Lapperre T, Bojesen RD, Eklöf J, Browatzki A, Wilcke JT, Gottlieb V, Håkansson KEJ, Tidemandsen C, et al. 2022. Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomized double-blinded placebo-controlled trial. Eur Respir J. 59(1):2100752. doi: 10.1183/13993003.00752-2021.
   PubMed Web of Science ®Google Scholar
• Stasi C, Fallani S, Voller F, Silvestri C. 2020. Treatment for COVID-19: an overview. Eur J Pharmacol. 889:173644. doi: 10.1016/j.ejphar.2020.173644.
   PubMed Web of Science ®Google Scholar
• Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. 2020a. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 18(5):1094–1099. a doi: 10.1111/jth.14817.
   PubMed Web of Science ®Google Scholar
• Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, Wu Y, Xiao W, Liu S, Chen E, et al. 2020b. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 369:m1849. b doi: 10.1136/bmj.m1849.
   PubMed Web of Science ®Google Scholar
• Temple C, Hoang R, Hendrickson R. 2021. Toxic effects from ivermectin use associated with prevention and treatment of Covid-19. N Engl J Med. 385(23):2197–2198. doi: 10.1056/NEJMc2114907.
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, et al. 2020. Remdesivir in adults with severe COVID-19: a randomized, double-blind, placebo-controlled, multicenter trial. Lancet. 395(10236):1569–1578. doi: 10.1016/S0140-6736(20)31022-9.
   PubMed Web of Science ®Google Scholar
• [WHO] World Health Organization. 2023. WHO Coronavirus (COVID-19) Dashboard. [accessed 2023 July 12]. https://covid19.who.int/.
   Google Scholar
• Xu E, Xie Y, Al-Aly Z. 2023. Long-term gastrointestinal outcomes of COVID-19. Nat Commun. 14(1):983. doi: 10.1038/s41467-023-36223-7.
   PubMed Web of Science ®Google Scholar