Therapeutic Options and Critical Care Strategies in COVID-19 Patients; Where Do We Stand in This Battle?
School of Medicine Students' Journal,
Vol. 2 No. 2 (2020),
1 April 2020
AbstractA pandemic of COVID-19 made an appearance in Wuhan, China, in late December 2019 and rapidly became a serious concern worldwide, with killing more than 238000 people until 3rd May 2020. Given the fact that a vaccine against the virus probably won’t be available anytime in the near future, the therapeutic strategies have become more prominent. Many supposedly effective drugs are under evaluation which may hinder the replication of SARS-CoV-2, and subsequently the infection. Lately on 1th may 2020, FDA authorized the use of experimental drug, Remdesivir for "emergency purpose" in COVID-19 cases. Chloroquine and hydroxychloroquine, among the very first under-trial drugs, have been revealed to have promising impacts in treatment of SARS-CoV2. Broad-spectrum antivirals as well as HIV protease-inhibitors are still subject to assessment. Particularly angiotensin-converting enzyme 2 (ACE2) inhibitors are increasingly taken into consideration because of ACE2 being recognized as a host-cell receptor for COVID-19. Immune-Enhancement therapy by Interferons and Intravenous immunoglobulin (IVIG) has been shown to be effective in some cases. Moreover, Convalescent Plasma Therapy and auxiliary blood purification were considered as the treatment of SARS-CoV2 infection. Among the critically ill patients, Oxygen-therapy, timely usage of inflammatory inhibitors, and controlling viral shedding by antivirals may reduce the mortality and morbidity of COVID-19.
How to Cite
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020:102433.
Watkins J. Preventing a covid-19 pandemic. Bmj. 2020;368:m810.
World Health O. Coronavirus disease 2019 (COVID-19): situation report, 104. 2020.
Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, 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.
Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1-9.
Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020.
Su B, Wang Y, Zhou R, Jiang T, Zhang H, Li Z, et al. Efficacy and Tolerability of Lopinavir/Ritonavir- and Efavirenz-Based Initial Antiretroviral Therapy in HIV-1-Infected Patients in a Tertiary Care Hospital in Beijing, China. Front Pharmacol. 2019;10:1472.
Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, et al. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication. Proc Natl Acad Sci U S A. 2008;105(42):16119-24.
Chu CM, Cheng VC, Hung IF, Wong MM, 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.
Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. 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.
Han W, Quan B, Guo Y, Zhang J, Lu Y, Feng G, et al. The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019. J Med Virol. 2020;92(5):461-3.
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.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020.
Best BM, Capparelli EV, Diep H, Rossi SS, Farrell MJ, Williams E, et al. Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children. J Acquir Immune Defic Syndr. 2011;58(4):385-91.
N e w s : A b i d o l a n d d a r u n a v i r c a n e f f e c t i v e l y inhibit coronavirus (accessed February 21,2020) (in Chinese). http://www.sd.chinanews.com/2/2020/0205/70145.html.
Shanghai Institute of Materia Medica website, ChineseAcademy of Sciences. A joint research team of the Shanghai Institute of Materia Medica and ShanghaiTech University discover a group of old and traditional Chinese medicines that may be efficacious in treating the novel form of pneumonia. http://www.simm.ac.cn/xwzx/kydt/202001/t20200125_5494417.html (accessed February22, 2020) (in Chinese).
Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018;153:85-94.
Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-63.
Liying Dong SH, Jianjun Gao. Discovering drugs to treat coronavirus disease 2019 (COVID-19). J-STAGE. 2020;14(1):58-60.
Mulangu S, Dodd LE, Davey RT, Jr., Tshiani Mbaya O, Proschan M, Mukadi D, et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019;381(24):2293-303.
Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381-5.
Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222.
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.
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First Case of 2019 Novel Coronavirus in the United States. New England Journal of Medicine. 2020;382(10):929-36.
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).
Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 2006;6(2):67-9.
Jang CH, Choi JH, Byun MS, Jue DM. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford). 2006;45(6):703-10.
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.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, 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.
Boriskin YS, Leneva IA, Pécheur EI, Polyak SJ. Arbidol: a broad-spectrum antiviral compound that blocks viral fusion. Curr Med Chem. 2008;15(10):997-1005.
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.
Deng L, Li C, Zeng Q, Liu X, Li X, Zhang H, et al. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. J Infect. 2020.
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020;14(1):69-71.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
Tan EL, Ooi EE, Lin CY, Tan HC, Ling AE, Lim B, et al. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis. 2004;10(4):581-6.
Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016;9(3):227-30.
Gamiño-Arroyo AE, Guerrero ML, McCarthy S, Ramírez-Venegas A, Llamosas-Gallardo B, Galindo-Fraga A, et al. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness. Clinical Infectious Diseases. 2019;69(11):1903-11.
Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. Jama. 2003;290(24):3222-8.
Mustafa S, Balkhy H, Gabere MN. Current treatment options and the role of peptides as potential therapeutic components for Middle East Respiratory Syndrome (MERS): A review. J Infect Public Health. 2018;11(1):9-17.
Chan KW, Wong VT, Tang SCW. COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Am J Chin Med. 2020:1-26.
Sainz B, Jr., Mossel EC, Peters CJ, Garry RF. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Virology. 2004;329(1):11-7.
Arabi YM, Shalhoub S, Mandourah Y, Al-Hameed F, Al-Omari A, Al Qasim E, et al. Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study. Clin Infect Dis. 2019.
Gilardin L, Bayry J, Kaveri SV. Intravenous immunoglobulin as clinical immune-modulating therapy. Cmaj. 2015;187(4):257-64.
Kumar V, Jung YS, Liang PH. Anti-SARS coronavirus agents: a patent review (2008 - present). Expert Opin Ther Pat. 2013;23(10):1337-48.
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-38.
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 study. Lancet. 2020.
Rubbert-Roth A, Furst DE, Nebesky JM, Jin A, Berber E. A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases. Rheumatol Ther. 2018;5(1):21-42.
National Health Commission (NHC) of the People’s Republic of China. The diagnosis and treatment guide of COVID-19 pneumonia caused by new coronavirus infection 7th Edition, published March 3rd, 2020. Translanted to English. http://www.gov.cn/zhengce/zhengceku/2020-03/04/content_5486705.htm.
Park JH, Romero FA, Taur Y, Sadelain M, Brentjens RJ, Hohl TM, et al. Cytokine Release Syndrome Grade as a Predictive Marker for Infections in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Chimeric Antigen Receptor T Cells. Clin Infect Dis. 2018;67(4):533-40.
Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS Med. 2006;3(9):e343.
Chen RC, Tang XP, Tan SY, Liang BL, Wan ZY, Fang JQ, et al. Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience. Chest. 2006;129(6):1441-52.
Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, 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.
Auyeung TW, Lee JS, Lai WK, Choi CH, Lee HK, Lee JS, et al. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: a retrospective cohort study. J Infect. 2005;51(2):98-102.
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.
National Health Commission (NHC) of the People’s Republic of China. The diagnosis and treatment guide of COVID-19 pneumonia caused by new coronavirus infection 7th Edition, published March 3rd, 2020. Translanted to English. .
Lin L, Li TS. [Interpretation of "Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)"]. Zhonghua Yi Xue Za Zhi. 2020;100(0):E001.
Marano G, Vaglio S, Pupella S, Facco G, Catalano L, Liumbruno GM, et al. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016;14(2):152-7.
Ankcorn M, Gallacher J, Ijaz S, Taha Y, Harvala H, Maclennan S, et al. Convalescent plasma therapy for persistent hepatitis E virus infection. J Hepatol. 2019;71(2):434-8.
Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52(4):447-56.
Khan MA, Bass DM. Viral infections: new and emerging. Curr Opin Gastroenterol. 2010;26(1):26-30.
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.
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7.
Tikellis C, Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease. Int J Pept. 2012;2012:256294.
Thomson G. COVID-19: social distancing, ACE 2 receptors, protease inhibitors and beyond? Int J Clin Pract. 2020:e13503.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
chen dL, Xiaokuni & song, qifa & Hu, Chenchan & Su, Feifei & Dai, Jianyi. . Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19). 2020; 10.1101/2020.02.27.20028530. .
Yang P, Gu H, Zhao Z, Wang W, Cao B, Lai C, et al. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci Rep. 2014;4:7027.
Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875-9.
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. Jama. 2020.
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74.
Zhang W, Chen X, Huang L, Lu N, Zhou L, Wu G, et al. Severe sepsis: Low expression of the renin-angiotensin system is associated with poor prognosis. Exp Ther Med. 2014;7(5):1342-8.
Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl. 2002(82):S12-22.
Meng J, Xiao G, Zhang J, He X, Ou M, Bi J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757-60.
Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):4.
Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet. 2020;395(10229):1014-5.
Wax RS, Christian MD. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Can J Anaesth. 2020.
Narendra DK, Hess DR, Sessler CN, Belete HM, Guntupalli KK, Khusid F, et al. Update in Management of Severe Hypoxemic Respiratory Failure. Chest. 2017;152(4):867-79.
Renda T, Corrado A, Iskandar G, Pelaia G, Abdalla K, Navalesi P. High-flow nasal oxygen therapy in intensive care and anaesthesia. Br J Anaesth. 2018;120(1):18-27.
Arabi YM, Fowler R, Hayden FG. Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med. 2020;46(2):315-28.
Bello G, De Pascale G, Antonelli M. Noninvasive Ventilation. Clin Chest Med. 2016;37(4):711-21.
Meng L, Qiu H, Wan L, Ai Y, Xue Z, Guo Q, et al. Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan's Experience. Anesthesiology. 2020.
MacLaren G, Fisher D, Brodie D. Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation. Jama. 2020.
Ramanathan K, Antognini D, Combes A, Paden M, Zakhary B, Ogino M, et al. Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Lancet Respir Med. 2020.
Xie J, Tong Z, Guan X, Du B, Qiu H, Slutsky AS. Critical care crisis and some recommendations during the COVID-19 epidemic in China. Intensive Care Medicine. 2020.
Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. 2020.
Yoo JS, Kato H, Fujita T. Sensing viral invasion by RIG-I like receptors. Curr Opin Microbiol. 2014;20:131-8.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-84.
Chen C, Zhang XR, Ju ZY, He WF. [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]. Zhonghua Shao Shang Za Zhi. 2020;36(0):E005.
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