Adverse Events Associated with COVID-19 Treatments and their Possible Relationship with Patient Characteristics: A Narrative Review

Omar Yahya Al-Shargi Samah Mukhlef Alzaid Bodoor Saud Al-Dosari Abeer Saad Alzubaidi   

Open Access   

Published:  Jan 10, 2023

DOI: 10.7324/JAPS.2023.105521

The adverse events (AEs) of repurposed drugs used in coronavirus disease 2019 (COVID-19) bear a challenge in clinical practice, even though the safety profiles of these drugs are quite known for primary indications. Since it is a new virus, post-marketing surveillance of drugs’ safety is of utmost clinical significance. This review aimed to investigate the patterns, incidence, and frequency of AEs of COVID-19 medications and vaccines and to explore the relationship between the occurrence of AEs and characteristics of COVID-19 patients, such as age, gender, and comorbidities. A literature search was conducted on electronic databases like MEDLINE, Google Scholar, and ScienceDirect for studies conducted on the AEs of drugs and vaccines used against COVID-19. The study found that prescription drugs for COVID-19 most commonly cause gastrointestinal symptoms, while some were associated with more severe liver, kidney, and cardiac manifestations. AEs varied among individuals, especially in elderly people with comorbidities. The known side effects of steroids and azithromycin including psychosis and prolongation of QT interval were also found to be prevalent when used in COVID-19 patients. Serious AEs such as multiple organ dysfunction syndrome (MODS) and septic shock were commonly reported among patients who required invasive ventilation. AEs reports for newly formulated vaccines showed general safety with the majority being local complaints. The reported AEs ranged from mild to severe, including MODS. Factors such as old age and comorbidities were found to be risk factors for a higher potentiality of AEs. Further studies are needed to draw evidence-based conclusions.

Keyword:     SARS-CoV-2 COVID-19 adverse events drug repurposing vaccines patient characteristics


Al-Shargi OY, Alzaid S M, Al-Dosari B S, Alzubaidi A S. Adverse events associated with COVID-19 treatment and its possible relationship with patient characteristics: A narrative review. J Appl Pharm Sci, 2023.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abdelazim AH, Ramzy S. Spectrophotometric quantitative analysis of remdesivir using acid dye reagent selected by computational calculations. Spectrochim Acta Part A Mol, 2022; 276:121188.

Aggarwal S, Garcia-Telles N, Aggarwal G, Lavie C, Lippi G, Henry BM. Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): early report from the United States. Diagnosis (Berl), 2020; 7:91-6.

Al-Shargi O, Saghir S, Al-Balagi N, Khan A. Knowledge assessment of symptoms identification of acute heart attack among staff and students of University Sains Malaysia. Int J Pharm Sci Rev Res, 2020; 65:1-9.

Al Kaabi N, Zhang Y, Xia S, Yang Y, Al Qahtani MM, Abdulrazzaq N, Al Nusair M, Hassany M, Jawad JS, Abdalla J, Hussein SE, Al Mazrouei SK, Al Karam M, Li X, Yang X, Wang W, Lai B, Chen W, Huang S, Wang Q, Yang T, Liu Y, Ma R, Hussain ZM, Khan T, Saifuddin Fasihuddin M, You W, Xie Z, Zhao Y, Jiang Z, Zhao G, Zhang Y, Mahmoud S, ElTantawy I, Xiao P, Koshy A, Zaher WA, Wang H, Duan K, Pan A, Yang X. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA, 2021; 326:35-45.

Alomar MJ. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J, 2014; 22:83-94.

Alshargi O, Alzaid S, Albahouth Z, Jaber A, Al-Dosari B. Clinical applications of pharmacometabonomics in neurology: current status, future perspectives and challenges. Res J Pharm Technol, 2022; 15:976-80.

Alshargi O, Jatau Abubakar I, Sha'aban A. Drug-related problems in emergency department visits and intensive care units at healthcare facilities in Saudi Arabia: a review of the literature. Malays J Pharm Sci, 2021; 19:153-69.

Brown MJ, Alazawi W, Kanoni S. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med, 2021; 385:1147.

Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events. JAMA, 2006; 296:1858-66.

Calderón-Larrañaga A, Vetrano DL, Onder G, Gimeno-Feliu LA, Coscollar-Santaliestra C, Carfí A, Pisciotta MS, Angleman S, Melis RJF, Santoni G, Mangialasche F, Rizzuto D, Welmer AK, Bernabei R, Prados- Torres A, Marengoni A, Fratiglioni L. Assessing and measuring chronic multimorbidity in the older population: a proposal for its operationalization. J Gerontol A Biol Sci Med Sci, 2017; 72:1417-23.

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res, 2020; 178:104787.

Campbell R, Tycon L, Pruskowski J. Corticosteroid-induced psychiatric symptoms #323. J Palliat Med, 2017; 20:298-9.

Cornelius AP. Adverse drug reactions in the era of COVID-19. Intern Emerg Med, 2021; 16:549-50.

Dutta S, Kaur RJ, Charan J, Bhardwaj P, Sharma P, Ambwani S, Haque M, Tandon A, Abhayanand JP, Sukhija S, Suman SV, Misra S. Serious adverse events reported from the COVID-19 vaccines: a descriptive study based on WHO database. medRxiv, 2021.03.23.21253433.

Falcão F, Viegas E, Carmo I, Soares J, Falcao M, Solano M, Cavaco P, Mendes D, Rijo J, Povoa P, Pais Martins A, Carmo E, Mansinho K, Fonseca C, Campos L, Carvalho A, Mirco A, Farinha H, Aldir I, Correia J. A prospective, observational study to evaluate adverse drug reactions in patients with COVID-19 treated with remdesivir or hydroxychloroquine: a preliminary report. Eur J Hosp Pharm, 2021; 28:248-53.

Food and Drug Administration. Emergency use auauthorization. [Online]. 2021a. Available via emergency-use-authorization (Accessed 6 July 2021).

Food and Drug Administration. FDA approves first treatment for COVID-19 [Online]. 2021b. Available via news-events/press-announcements/fda-approves-first-treatment-covid-19 (Accessed 6 July 2021).

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, 2020; 56:105949.

Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ, 2020; 11:29.

Gee J, Marquez P, Su J, Calvert GM, Liu R, Myers T, Nair N, Martin S, Clark T, Markowitz L, Lindsey N, Zhang B, Licata C, Jazwa A, Sotir M, Shimabukuro T. First month of covid-19 vaccine safety monitoring-United States, December 14, 2020-January 13, 2021. MMWR Morb Mortal Wkly Rep, 2021; 70:283-8.

Gérard A, Romani S, Fresse A, Viard D, Parassol N, Granvuillemin A, Chouchana L, Rocher F, Drici MD. "Off-label" use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapie, 2020; 75:371-9.

Ghasemiyeh P, Borhani-Haghighi A, Karimzadeh I, Mohammadi- Samani S, Vazin A, Safari A, Qureshi AI. Major Neurologic adverse drug reactions, potential drug-drug interactions and pharmacokinetic aspects of drugs used in COVID-19 patients with stroke: a narrative review. Ther Clin Risk Manag, 2020; 16:595-605.

Gordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol, 2021; 12:2040620721989588.

Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX, Nicastri E, Oda R, Yo K, Quiros- Roldan E, Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara S, Cohen SH, Cunningham J, D'Arminio Monforte A, Ismail S, Kato H, Lapadula G, L'Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M, Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y, Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I, Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A, Myers RP, Brainard DM, Childs R, Flanigan T. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med, 2020; 382:2327-36.

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DS. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020; 382:1708-20.

Heo J, Han D, Kim HJ, Kim D, Lee YK, Lim D, Hong SO, Park MJ, Ha B, Seog W. Prediction of patients requiring intensive care for COVID-19: development and validation of an integer-based score using data from Centers for Disease Control and Prevention of South Korea. J Intensive Care, 2021; 9:16.

Iftimie S, López-Azcona AF, Vallverdú I, Hernández-Flix S, de Febrer G, Parra S, Hernández-Aguilera A, Riu F, Joven J, Andreychuk N, Baiges-Gaya G, Ballester F, Benavent M, Burdeos J, Català A, Castañé È, Castañé H, Colom J, Feliu M, Gabaldó X, Garrido D, Garrido P, Gil J, Guelbenzu P, Lozano C, Marimon F, Pardo P, Pujol I, Rabassa A, Revuelta L, Ríos M, Rius-Gordillo N, Rodríguez-Tomàs E, Rojewski W, Roquer- Fanlo E, Sabaté N, Teixidó A, Vasco C, Camps J, Castro A. First and second waves of coronavirus disease-19: a comparative study in hospitalized patients in Reus, Spain. PLoS One, 2021; 16:e0248029.

Izcovich A, Siemieniuk RAC, Bartoszko JJ, Ge L, Zeraatkar D, Kum E, Khamis AM, Rochwerg B, Agoritsas T, Chu DK, Mcleod SL, Mustafa RA, Vandvik PO, Brignardello-Petersen R. Adverse effects of remdesivir, hydroxychloroquine, and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomized trials. medRxiv, 2020.11.16.20232876.

Jin JM, Bai P, He W, Wu F, Liu XF, Han DM, Liu S, Yang JK. Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health, 2020; 8:152.

Jing Y, Diao L, Han L. Adverse events associated with potential drugs for COVID-19: a case study from real-world data. Brief Bioinform, 2021; 22:1232-8.

Kaur RJ, Dutta S, Bhardwaj P, Charan J, Dhingra S, Mitra P, Singh K, Yadav D, Sharma P, Misra S. Adverse events reported from COVID-19 vaccine trials: a systematic review. Indian J Clin Biochem, 2021; 36:1-13.

Khan M, Gillani S. Corticosteroid induced generalized seizures in a nephrotic child with iatrogenic cushing syndrome. Pak Pediatr J, 2018; 42:136-40.

Khosa S, Khanlou N, Khosa GS, Mishra SK. Hydroxychloroquine-induced autophagic vacuolar myopathy with mitochondrial abnormalities. Neuropathology, 2018; 38:646-52.

Kim MWT. Update on azithromycin and cardiac side effects metastatic pulmonary calcification. SWRCCC, 2014; 2:4.

Koryürek ÖM, Kalkan G. A new alternative therapy in dermatology: tocilizumab. Cutan Ocul Toxicol, 2016; 35:145-52.

Krzeminski P, Lesiak A, Narbutt J. Seizures as a rare adverse effect of chloroquine therapy in systemic lupus erythematosus patients: a case report and literature survey. Postepy Dermatol Alergol, 2018; 35:429-30.

Li X, Ostropolets A, Makadia R, Shaoibi A, Rao G, Sena AG, Martinez-Hernandez E, Delmestri A, Verhamme K, Rijnbeek PR, Duarte- Salles T, Suchard M, Ryan P, Hripcsak G, Prieto-Alhambra D. Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study. medRxiv, 2021.03.25.21254315.

Lim SCL, Hor CP, Tay KH, Mat Jelani A, Tan WH, Ker HB, Chow TS, Zaid M, Cheah WK, Lim HH, Khalid KE, Cheng JT, Mohd Unit H, An N, Nasruddin AB, Low LL, Khoo SWR, Loh JH, Zaidan NZ, Ab Wahab S, Song LH, Koh HM, King TL, Lai NM, Chidambaram SK, Peariasamy KM, I-TECH Study Group. Efficacy of ivermectin treatment on disease progression among adults with mild to moderate COVID-19 and comorbidities: the I-TECH randomized clinical trial. JAMA Intern Med, 2022; 182:426-35.

Manivannan E, Karthikeyan C, Moorthy N, Chaturvedi SC. The rise and fall of chloroquine/hydroxychloroquine as compassionate therapy of COVID-19. Front Pharmacol, 2021; 12:584940.

Melo JRR, Duarte EC, Moraes MV, Fleck K, Silva A, Arrais PSD. Adverse drug reactions in patients with COVID-19 in Brazil: analysis of spontaneous notifications of the Brazilian pharmacovigilance system. Cad Saude Publica, 2021; 37:e00245820.

Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, Sudre CH, Nguyen LH, Drew DA, Merino J, Hu C, Selvachandran S, Antonelli M, Murray B, Canas LS, Molteni E, Graham MS, Modat M, Joshi AD, Mangino M, Hammers A, Goodman AL, Chan AT, Wolf J, Steves CJ, Valdes AM, Ourselin S, Spector TD. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis, 2021; 21:939-49.

Mota DM, Kuchenbecker RS. Causality in pharmacoepidemiology and pharmacovigilance: a theoretical excursion. Rev Bras Epidemiol, 2017; 20:475-86.

National Institute Of Health. Therapeutic management of adults with COVID-19 [Online]. 2021. Available via https://www. (Accessed 6 July 2021).

Parmar RC, Valvi CV, Kamat JR, Vaswani RK. Chloroquine induced parkinsonism. J Postgrad Med, 2000; 46:29-30.

Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, Scarlata S, Agro FE. COVID-19 diagnosis and management: a comprehensive review. J Intern Med, 2020; 288:192-206.

Ramireddy A, Chugh H, Reinier K, Ebinger J, Park E, Thompson M, Cingolani E, Cheng S, Marban E, Albert CM, Chugh SS. Experience with hydroxychloroquine and azithromycin in the coronavirus disease 2019 pandemic: implications for qt interval monitoring. J Am Heart Assoc, 2022; 9:e017144.

Ramírez E, Urroz M, Rodríguez A, González-Muñoz M, Martín- Vega A, Villán Y, Seco E, Monserrat J, Frías J, Carcas AJ, Borobia AM. Incidence of suspected serious adverse drug reactions in corona virus disease-19 patients detected by a pharmacovigilance program by laboratory signals in a tertiary hospital in Spain: cautionary data. Front Pharmacol, 2020; 11:602841.

Recovery Collaborative Group. Dexamethasone for COVID-19: preliminary findings. Drug Ther Bull, 2020; 58:133.

Reis G, Silva EASM, Silva DCM, Thabane L, Milagres AC, Ferreira TS, Dos Santos CVQ, Campos VHS, Nogueira AMR, de Almeida APFG, Callegari ED, Neto ADF, Savassi LCM, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ; TOGETHER Investigators. Effect of early treatment with ivermectin among patients with Covid-19. N Engl J Med, 2022; 386:1721-31.

Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, Skiest D, Aziz MS, Cooper N, Douglas IS, Savic S, Youngstein T, Del Sorbo L, Cubillo Gracian A, De La Zerda DJ, Ustianowski A, Bao M, Dimonaco S, Graham E, Matharu B, Spotswood H, Tsai L, Malhotra A. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N Engl J Med, 2021; 384:1503-16.

Saito S, Asai Y, Matsunaga N, Hayakawa K, Terada M, Ohtsu H, Tsuzuki S, Ohmagari N. First and second COVID-19 waves in Japan: a comparison of disease severity and characteristics. J Infect, 2021; 82:84-123.

Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, Criner GJ, Kaplan-Lewis E, Baden R, Pandit L, Cameron ML, Garcia-Diaz J, Chávez V, Mekebeb-Reuter M, Lima de Menezes F, Shah R, González- Lara MF, Assman B, Freedman J, Mohan SV. Tocilizumab in patients hospitalized with COVID-19 pneumonia. N Engl J Med, 2021; 384:20-30.

Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LC, Berwanger O, Cavalcanti AB, Dequin PF. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA, 2020; 324:1330-41.

Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, Felix SE, Tie Y, Fullerton KE. Coronavirus disease 2019 case surveillance- United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep, 2020; 69:759-65.

Sun J, Deng X, Chen X, Huang J, Huang S, Li Y, Feng J, Liu J, He G. Incidence of adverse drug reactions in COVID-19 patients in China: an active monitoring study by hospital pharmacovigilance system. Clin Pharmacol Ther, 2020; 108:791-7.

Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, Minhas JS, Divall P, Khunti K, Abrams KR, Nellums LB, Pareek M. Ethnicity and clinical outcomes in COVID-19: a systematic review and meta-analysis. EClinicalMedicine, 2020; 29:100630.

Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, Avezum A, Lopes RD, Bueno FR, Silva MVAO, Baldassare FP, Costa ELV, Moura RAB, Honorato MO, Costa AN, Damiani LP, Lisboa T, Kawano-Dourado L, Zampieri FG, Olivato GB, Righy C, Amendola CP, Roepke RML, Freitas DHM, Forte DN, Freitas FGR, Fernandes CCF, Melro LMG, Junior GFS, Morais DC, Zung S, Machado FR, Azevedo LCP, COALITION COVID-19 Brazil III Investigators. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: The CoDEX randomized clinical trial. JAMA, 2020; 324:1307-16.

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, 2020; 395:1569-78.

Wise J. COVID-19: people who have had infection might only need one dose of mRNA vaccine. BMJ, 2021; 372:n308.

World Health Organization. Med Safety App to report adverse reactions-contribution in the COVID-19 pandemic. [Online]. 2021a. Available via pharmacovigilance (Accessed 12 July 2021).

World Health Organization. The true death toll of COVID-19. Estimating global excess mortality [Online]. 2021b. Available via https:// (Accessed 8 July 2021).

World Health Organization. WHO coronavirus (COVID-19) statsitics [Online]. 2022. Available via (Accessed 28 May 2022).

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. 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; 71:732-9.

Zekarias A, Watson S, Vidlin SH, Grundmark B. Sex differences in reported adverse drug reactions to COVID-19 drugs in a global database of individual case safety reports. Drug Saf, 2020; 43:1309-14.

Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, Zhang Z. D-dimer levels on admission to predict in-hospital mortality in patients with COVID-19. J Thromb Haemost, 2020; 18:1324-9.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020; 395:1054-62.

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