Pharmacologic agents for the management of COVID-19: a review

Authors

  • Syeda Maria Hassan Jinnah Sindh Medical University, Karachi, Sindh, Pakistan
  • Hamza Sohail Jinnah Sindh Medical University, Karachi, Sindh, Pakistan
  • Abeer Iftikhar Jinnah Sindh Medical University, Karachi, Sindh, Pakistan
  • Rabia Rathore Jinnah Sindh Medical University, Karachi, Sindh, Pakistan
  • Qandeel Fatima Jinnah Sindh Medical University

DOI:

https://doi.org/10.18203/2394-6040.ijcmph20205735

Keywords:

Coronavirus, COVID-19, SARS-CoV-2, Treatment, Pakistan

Abstract

Coronavirus, in December 2019, caused a SARS-2 pandemic. Primarily targeting the human respiratory system, the major symptoms of this disease are high grade fever, dry cough, shortness of breath, sore throat, and fatigue while symptoms involving other organ systems such as diarrhea, headache, conjunctivitis, and rash also develops. Like a SARS-CoV-1 outbreak in 2002, SARS-CoV-2 is difficult to treat as minimal data is available regarding its treatment strategies and potential cure of the disease. A thorough literature review was done to identify different potential treatments for SARS-CoV-2 and a perspective of a developing country, Pakistan, on managing and treating this infection was provided. We found that use of off-label drugs including including chloroquine, hydroxychloroquine, remdesivir, azithromycin, interferon, ribavirin, lopinavir-ritonavir, increased exponentially to treat COVID-19 patients around the world and studies suggested their efficacy against SARS-CoV-2. Use of adjunctive therapies including convalescent plasma, interferons, and corticosteroids also showed positive results in slowing down the progression of the disease. Different clinical trials are being conducted around the world to identify drugs and develop vaccine against infection caused by this deadly virus. Use of these off-label drugs and adjunctive therapies was also seen in a developing Country like Pakistan, which need desperate measures to overcome COVID-19 disease burden on the country’s people and the economy. Coronavirus is infecting thousands of people daily, worldwide. Major action including upgrading medical facilities, investing in health care sector, developing effective drugs, must be taken in both developed and developing countries like Pakistan to fight, contain and prevent future pandemics.

References

Salata C, Calistri A, Parolin C, Palù G. Coronaviruses: a paradigm of new emerging zoonotic diseases. Pathog Dis. 2019;77(9):6.

Sohrabi C, Alsafi Z, O'Neill N, Khan M, Kerwan A, Al-Jabir A, et al. World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19). Int J Surg. 2020;76:71‐6.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort. Lancet. 2020;395(10229):1054-62.

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-90.

Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433.

Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809‐15.

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172(9):577‐82.

Ahn DG, Shin HJ, Kim MH, Lee S, Kim HS, Myoung J, et al. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol. 2020;30(3):313‐24.

Li Y, Xia L. Coronavirus disease 2019 (COVID-19): role of chest CT in diagnosis and management. AJR Am J Roentgenol. 2020;214(6):1280-6.

Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3(9):e343.

World Health Organization. Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update. 2020. Available at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed on 18 October 2020.

Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: a review. Clin Immunol. 2020;215:108427.

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-8.

Kalil AC. Treating COVID-19 off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA. 2020;323(19):1897-8.

Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases?. Lancet Infect Dis. 2003;3(11):722-7.

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): a review. JAMA. 2020;323(18):1824-36.

Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-3.

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, 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):105-9.

Chen J, Liu D, Liu L, Liu P, Xia L. A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020;49(2):215-9.

Wilde AH, Jochmans D, Posthuma CC, Zevenhoven JC, Nieuwkoop S, Bestebroer TM, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of middle east respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014;58(8):4875-84.

Chu CM, Cheng VCC, Hung IFN, Wong MML, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3):252-6.

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. Bio Sci Trends. 2020;14(1):64-8.

Chen J, Ling Y, Xi X, Liu P, Li F, Li T, et al. Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia. Chin J Infect Dis. 2020;38(0):E008.

Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-a possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6):556-63.

Knowles SR, Phillips EJ, Dresser L, Matukas L. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis. 2003;37(8):1139-42.

Kadam RU, Wilson IA. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc Natl Acad Sci USA. 2017;114(2):206-14.

Khamitov RA, Loginova S, Shchukina VN, Borisevich SV, Maksimov VA, Shuster AM. Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures. Vopr Virusol. 2008;53(4):9-13.

Cao J, Tu WJ, Cheng W, Yu L, Liu YK, Hu X, et al. Clinical Features and short-term outcomes of 102 patients with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis. 2020;71(15):748-55.

Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 2020;382(24):2327-36.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.

Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of inhibition of ebola virus rna-dependent RNA polymerase by remdesivir. Viruses. 2019;11(4):326.

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396):3653.

Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis. 2020;34:101615.

Clinicaltrials.gov. A trial of remdesivir in adults with mild and moderate COVID-19. 2020. Available at https://clinicaltrials.gov/ct2/show/NCT04252664. Accessed on 18 October 2020.

Fda.gov. Remdesivir EUA Letter of Authorization. 2020. Available at https:// www. fda.gov/ media/137564. Accessed on 18 October 2020.

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.

Chaccour C, Hammann F, García S, Rabinovich NR. Ivermectin and novel coronavirus disease (covid-19): keeping rigor in times of urgency. Am J Trop Med Hyg. 2020;102(6):1156-7.

Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851‐6.

Rowland RR, Chauhan V, Fang Y, Pekosz A, Kerrigan M, Burton MD. Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells. J Virol. 2005;79(17):11507‐12.

Choudhary R, Sharma AK. Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance. New Microbes New Infect. 2020;35:100684.

Bray M, Rayner C, Noël F, Jans D, Wagstaff K. Ivermectin and COVID-19: a report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses. Antiviral Res. 2020;178:104805.

Trailovic SM, Nedeljkovic JT. Central and peripheral neurotoxic effects of ivermectin in rats. J Vet Med Sci. 2011;73(5):591‐9.

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with covid-19 with convalescent plasma. JAMA. 2020;323(16):1582-9.

Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA. 2020;117(17):9490-6.

Cao W, Liu X, Bai T, Fan H, Hong K, Song H, et al. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. Open Forum Infect Dis. 2020;7(3):102.

Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. The Lancet Infect Dis. 2020;20(6):689-96.

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, 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.

Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395(10223):473-5.

World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020. 2020. Available at https:// apps. who. int/ iris/ handle/ 10665/330893. Accessed on 18 October 2020.

Voiriot G, Philippot Q, Elabbadi A, Elbim C, Chalumeau M, Fartoukh M. risks related to the use of non-steroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med. 2019;8(6):786.

Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020;368:1185.

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.

Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase iii trial. Crit Care Med. 2016;44(2):275-81.

Chinese clinical trial registry. A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). 2020. Available at: http:// www. chictr. org.cn /showprojen.aspx?proj=49409. Accessed on 18 October 2020.

Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395(10223):e30‐e31.

Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al Evidence that Vitamin D supplementation could reduce risk of influenza and covid-19 infections and deaths. Nutrients. 2020;12(4):988.

Rondanelli M, Miccono A, Lamburghini S, Avanzato I, Riva A, Allegrini P, et al. Self-care for common colds: the pivotal role of vitamin d, vitamin c, zinc, and echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds-practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evid Based Complement Alternat Med. 2018;2018:5813095.

Baglivo M, Baronio M, Natalini G, Beccari T, Chiurazzi P, Fulcheri E, et al. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?. Acta Biomed. 2020;91(1):161-4.

Hoffmann M, Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ace2 and tmprss2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-80.

Xiao L, Sakagami H, Miwa N. ACE2: the key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: Demon or Angel?. Viruses. 2020;12(5):491.

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Published

2020-12-25

How to Cite

Hassan, S. M., Sohail, H., Iftikhar, A., Rathore, R., & Fatima, Q. (2020). Pharmacologic agents for the management of COVID-19: a review. International Journal Of Community Medicine And Public Health, 8(1), 446–452. https://doi.org/10.18203/2394-6040.ijcmph20205735

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Section

Review Articles