TY  - JOUR
T1  - COVID-19 Tedavisine Yönelik Güncel Farmakolojik Yaklaşımlar
TT  - Current Pharmacological Approaches To COVID-19 Treatment
AU  - Eroğlu, Ezgi
AU  - Balcı, Hakan
AU  - Baskın, Veysel
AU  - Aktuna, Zuhal
PY  - 2021
DA  - April
DO  - 10.51261/yiu.2021.00018
JF  - Yüksek İhtisas Üniversitesi Sağlık Bilimleri Dergisi
JO  - YIU Saglik Bil Derg
PB  - Yüksek İhtisas Üniversitesi
WT  - DergiPark
SN  - 2717-8439
SP  - 1
EP  - 15
VL  - 2
IS  - 1
LA  - tr
AB  - Şiddetli akut solunum sendromu koronavirüs 2’nin  SARS-CoV-2   neden olduğu mevcut koronavirüs hastalığı 2019  COVID-19  salgını,  2019 yılının son aylarında Çin’in Wuhan kentindeki toptancı pazarında  ortaya çıkmış ve dünyanın hemen hemen tüm ülkelerine yayılmıştır.  COVID-19’un şu anda spesifik bir tedavisi bulunmamakla birlikte, in  vitro, in vivo çalışmalar ve randomize kontrollü çalışmalara dayalı olarak  tüm dünyada belirli ilaçlar kullanılmaktadır. Bu derlemede, COVID-19  tedavisi için kullanılan bu ilaçlar hakkında kısa bilgiler, yapılan  araştırmaların sonuçları ve ilaçların olası yan etkileri özetlenmiştir.  Hazırladığımız bu derlemenin, SARS-CoV-2’yi hedefleyen aşıların ve  spesifik ilaçların onaylanmasına kadar COVID-19 hastalarını tedavi  etmek ve hastalığı kontrol altına almak için kullanılan en güncel  terapötik ilaçlar hakkında bir izlenim sağlayacağını umuyoruz.
KW  - COVID-19
KW  - SARS CoV-2
KW  - farmakoterapötikler
N2  - The current outbreak of coronavirus disease 2019  COVID-19  caused  by severe acute respiratory syndrome coronavirus 2  SARS-CoV-2   occurred in the wholesale market in Wuhan, China in the last months of  2019 and spread to almost all countries in the world. Although there is  currently no specific treatment for COVID-19, certain agents are used  worldwide, based on in vitro, in vivo studies, and randomized controlled  trials. In this review, brief information about these drugs used for the  treatment of COVID-19, the results of the conducted studies and the  possible adverse effects of the drugs are summarized. We hope that this  review will provide an impression of the most current therapeutic drugs  used to prevent, control and treat COVID-19 patients until the approval  of vaccines and specific drugs targeting SARS-CoV-2.
CR  - Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2  SARS-CoV-2  and coronavirus disease-2019  COVID-19 : The epidemic and the challenges. Int J Antimicrob Agents 2020;55:105924. https://doi.org/10.1016/j.ijantimicag.2020.105924
CR  - Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease  COVID-19 : a multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80:388– 393. https://doi.org/10.1016/j.jinf.2020.02.016
CR  - Chan JFW, Kok KH, Zhu Z, Chu H, To KKW, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microb Infect 2020;9:221–236. https://doi.org/10.1080/22221751.2020.1719902
CR  - Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708–1720. https://doi.org/10.1056/NEJMoa2002032
CR  - Chan KS, Lai ST, Chu CM, Sui ET, Tam CY, Wong MML, et al. Treatment of severe acute respiratory syndrome with lopinavir/ ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J 2003;9:399–406. https://www.hkmj.org/system/files/hkm0312p399.pdf
CR  - Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199–1207. https://doi.org/10.1056/nejmoa2001316
CR  - Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270–273. https://doi.org/10.1038/s41586-020-2012-7
CR  - Corum J, Zimmer C. Bad news wrapped in protein: inside the coronavirus genome. New York: The New York Times Company; 2020. https://www. nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-newswrapped-in-protein.html
CR  - Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science  New York, NY  2020;367:1444–1448. https://doi.org/10.1126/science.abb2762
CR  - Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020;11:1620. https://doi.org/10.1038/s41467-020-15562-9
CR  - Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 2020;92:418–423. https://doi.org/10.1002/ jmv.25681
CR  - Fung TS, Liu DX. Human coronavirus: host-pathogen interaction. Annu Rev Microbiol 2019;73:529–557. https://doi.org/10.1146/annurevmicro-020518-115759
CR  - Lai CC, Liu YH, Wang CY, Wang YH, Hsueh SC, Yen MY, et al. Asymptomatic Carrier State, Acute Respiratory Disease, and Pneumonia Due to Severe Acute Respiratory Syndrome Coronavirus 2  SARS-CoV-2 : Facts and Myths. J Microbiol Immunol Infect 2020;53:404–412. https://doi.org/10.1016/j. jmii.2020.02.012
CR  - Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res 2014;59:118–128. https://doi. org/10.1007/s12026-014-8534-z
CR  - Nelemans T, Kikkert M. Viral innate immune evasion and the pathogenesis of emerging RNA virus infections. Viruses 2019;11:961. https://doi.org/10.3390/ v11100961
CR  - Newton AH, Cardani A, Braciale TJ. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol 2016;38:471–482. https://doi.org/10.1007/s00281-016-0558-0
CR  - CDC Groups at higher risk for severe illness. Center for Disease Control and Prevention  CDC  2020. https://www.cdc.gov/coronavirus/2019-ncov/ downloads/COVID19-What-You-Can-Do-High-Risk.pdf
CR  - Maragakis L. Coronavirus and COVID-19: who is at higher risk? Johns Hopkins Med 2020. https://www.hopkinsmedicine.org/health/conditions-anddiseases/coronavirus/coronavirus-and-covid19-who-is-at-higher-risk
CR  - Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med 2020;288:192–206. https://doi.org/10.1111/joim.13091
CR  - Sanders JM, Monogue ML, Judlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019  COVID-19 . JAMA 2020;323:1824– 1836. https://doi.org/10.1001/jama.2020.6019
CR  - Li G, Clercq ED. Therapeutic options for the 2019 novel coronavirus  2019- nCoV . Nat Rev Drug Discov 2020;19:149–150. https://doi.org/10.1038/ d41573-020-00016-0
CR  - Barlow A, Landolf KM, Barlow B, Yeung SYA, Heavner JJ, Claassen CW, et al. Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019. Pharmacotherapy 2020;40:416–437. https://doi.org/10.1002/ phar.2398
CR  - Paragas J, Blatt LM, Hartmann C, Huggins JW, Endy TP. Interferon alfacon1 is an inhibitor of SARS-corona virus in cell-based models. Antiviral Res 2005;66:99–102. https://doi.org/10.1016/j.antiviral.2005.01.002
CR  - Wang W, Ye L, Ye L, Li B, Gao B, Zeng Y, et al. Up-regulation of IL-6 and TNFalpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res 2007;128:1–8. https://doi.org/10.1016/j. virusres.2007.02.007
CR  - Rynes RI. Antimalarial drugs in the treatment of rheumatological diseases. Rheumatology 1997;36:799–805. https://doi.org/10.1093/ rheumatology/36.7.799
CR  - Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ 2020;369:m1432. https://doi.org/10.1136/bmj.m1432
CR  - Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis 2006;6:67–69. https://doi. org/10.1016/s1473-3099 06 70361-9
CR  - Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020;6:1–4. https://doi.org/10.1038/s41421- 020-0156-0
CR  - Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020;20:269–270. https://doi.org/10.1038/s41577-020-0308-3
CR  - Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies. Int J Antimicrob Agents 2020;55:105982. https://doi.org/10.1016/j.ijantimicag.2020.105982
CR  - Colson P, Rolain J-M, Lagier J-C, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020;55:105932. https://doi.org/10.1016/j.ijantimicag.2020.105932
CR  - Sinha N, Balayla G. Hydroxychloroquine and covid-19. Postgrad Med J 2020;96:550–555. https://doi.org/10.1136/postgradmedj-2020-137785
CR  - Gbinigie K, Frie K. Should Chloroquine and Hydroxychloroquine Be Used to Treat COVID-19? A Rapid Review. BJGP Open 2020;4:bjgpopen20X101069. https://doi.org/10.3399/bjgpopen20x101069
CR  - 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;93:449–463. https://doi.org/10.2183/pjab.93.027
CR  - Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir  T-705 , a novel viral RNA polymerase inhibitor. Antivir Res 2013;100:446–454. https://doi.org/10.1016/j.antiviral.2013.09.015
CR  - De Clercq E. New nucleoside analogues for the treatment of hemorrhagic fever virus infections. Chem Asian J 2019;14:3962–3968. https://doi.org/10.1002/ asia.201900841
CR  - Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, et al. Favipiravir versus arbidol for COVID-19: a randomized clinical trial. medRxiv 2020:2020. https://doi.org/10.1101/2020.03.17.20037432
CR  - Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019  COVID-19 . Drug Discov Ther 2020;14:58–60. https://doi.org/10.5582/ ddt.2020.01012
CR  - Tu YF, Chien CS, Yarmishyn AA, Lin YY, Luo YH, Lin YT, et al. A Review of SARS-CoV-2 and the Ongoing Clinical Trials. Int J Mol Sci 2020;21:2657. https://doi.org/10.3390/ijms21072657
CR  - ClinicalTrials.gov. US National Library of Medicine. https://clinicaltrials.gov/ ct2/results?cond=COVID19+favipiravir&term=&cntry=&state=&city=&dist=
CR  - Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, 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. https://doi. org/10.1016/j.ijid.2020.11.142
CR  - Pilkington V, Pepperrell T, Hill A. A review of the safety of favipiravir –a potential treatment in the COVID-19 pandemic? J Virus Erad 2020;6:45–51. https://doi.org/10.1016/s2055-6640 20 30016-9
CR  - Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2, 1-f][triazin4-amino] adenine C-nucleoside  GS-5734  for the treatment of Ebola and emerging viruses. J Med Chem 2017;60:1648–1661. https://doi.org/10.1021/ acs.jmedchem.6b01594
CR  - 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. https://doi.org/10.1016/j.tmaid.2020.101615
CR  - Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir  GS-5734  is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 2018;9:e00221–00218. https://doi.org/10.1128/mbio.00221-18
CR  - Sheahan TP, Sims AC, Leist SR, Schafer 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;11:222. https://doi.org/10.1038/s41467-019-13940-6
CR  - 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;30:269–271. https://doi.org/10.1038/s41422- 020-0282-0
CR  - Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020;382:929–936. https://doi.org/10.1056/nejmoa2001191
CR  - Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 –Final Report. N Engl J Med 2020;383:1813–1826. https://doi.org/10.1056/NEJMoa2007764
CR  - 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:eaal3653. https://doi.org/10.1126/ scitranslmed.aal3653
CR  - Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020;395:473– 475. https://doi.org/10.1016/s0140-6736 20 30317-2
CR  - Villar J, Belda J, Anon JM, Blanco J, Perez-Mendez L, Ferrando C, et al. Evaluating the efficacy of dexamethasone in the treatment of patients with persistent acute respiratory distress syndrome: study protocol for a randomized controlled trial. Trials 2016;17:342. https://doi.org/10.1186/s13063-016-1456- 4
CR  - Lamontagne F, Rochwerg B, Lytvyn L, Guyatt GH, Møller MH, Annane D, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ 2018;362: k3284. https://doi.org/10.1136/bmj.k3284
CR  - Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P, et al. Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China. medRxiv 2020;2020:20032342. https://doi.org/10.1101/2020.03.06.20032342
CR  - Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019- nCoV pneumonia. Lancet 2020;395:683–684. https://doi.org/10.1016/s0140- 6736 20 30361-5
CR  - Farkas J. Management of COVID-19 patients admitted to stepdown or ICU. Internet Book of Critical Care  IBCC . EMCrit Project. https://emcrit.org/ibcc/ covid19/
CR  - 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  Lond Engl  2020;395:497–506. https://doi.org/10.1016/s0140-6736 20 30183-5
CR  - Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC-C, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020;ciaa478. https:// doi.org/10.1093/cid/ciaa478
CR  - Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 2020;8:267–276. https://doi.org/10.1016/S2213-2600 19 30417-5
CR  - Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006;145:599–609. https://doi.org/10.7326/0003-4819-145-8- 200610170-00139
CR  - Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, et al. Retrospective comparison of convalescent plasma with continuing highdose methylprednisolone treatment in SARS patients. Clin Microbiol Infect 2004;10:676–678. https://doi.org/0.1111/j.1469-0691.2004.00956.x
CR  - 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;52:447–456. https://doi. org/10.1093/cid/ciq106
CR  - Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A  H5N1  infection. N Engl J Med 2007;357:1450–1451. https://doi.org/10.1056/ NEJMc070359
CR  - World Health Organization. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. Interim Guidance for National Health Authorities and Blood Transfusion Services; 2014. https://apps. who.int/iris/bitstream/handle/10665/135591/WHO_HIS_SDS_2014.8_eng. pdf?sequence=1&isAllowed=y
CR  - Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005;24:44–46. https://doi.org/10.1007/s10096-004-1271-9
CR  - Rajendran K, Krishnasamy N, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: Systematic review. J Med Virol 2020;92:1475–1483. https://doi. org/10.1002/jmv.25961
CR  - Peters DH, Friedel HA, McTavish D. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. Drugs 1992;44:750–799. https://doi.org/10.2165/00003495-199244050-00007
CR  - Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: Mechanisms of Action and Their Relevance for Clinical Applications. Pharmacol Ther 2014;143:225–245. https://doi.org/10.1016/j.pharmthera.2014.03.003
CR  - Poschet JF, Perkett EA, Timmins GS, Deretic V. Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells. bioRxiv 2020;3:008631. https://doi.org/10.1101/2020.03.29.008631
CR  - 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;56:105949. https://doi.org/10.1016/j.ijantimicag.2020.105949
CR  - Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, 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;50:384. https://doi.org/10.1016/j. medmal.2020.03.006
CR  - Wu R, Wang L, Kuo HCD, Shannar A, Peter R, Chou PJ, et al. An Update on Current Therapeutic Drugs Treating COVID-19. Curr Pharmacol Rep 2020;6:56–70. https://doi.org/10.1007/s40495-020-00216-7
CR  - Gbinigie K, Frie K. Should azithromycin be used to treat COVID-19? A rapid review. BJGP Open 2020;4:bjgpopen20X101094. https://doi.org/10.3399/ bjgpopen20x101094
CR  - Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs 2003;63:769–802. https://doi. org/10.2165/00003495-200363080-00004
CR  - Chan JFW, Yao Y, Yeung ML, Deng W, Bao L, Jia L, et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J Infect Dis 2015;212:1904–1913. https://doi.org/10.1093/infdis/jiv392
CR  - Kim UJ, Won EJ, Kee SJ, Jung SI, Jang HC. Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for Middle East respiratory syndrome. Antivir Ther 2016;21:455–459. https://doi.org/10.3851/imp3002
CR  - Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARSCoV-2 in Singapore. JAMA 2020;323:1488–1494. https://doi.org/10.1001/ jama.2020.3204
CR  - Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavirritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020;382:1787–1799. https://doi.org/10.1056/nejmoa2001282
CR  - Carr AC, Maggini S. Vitamin C and immune function. Nutrients 2017;9:1211. https://doi.org/10.3390/nu9111211
CR  - van Gorkom G, Klein Wolterink R, Van Elssen C, Wieten L, Germeraad W, Bos G. Influence of Vitamin C on lymphocytes: an overview. Antioxidants  Basel  2018;7:41. https://doi.org/10.3390/antiox7030041
CR  - Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019  COVID-19 ? Med Drug Discov 2020;5:100028. https://doi.org/10.1016/j.medidd.2020.100028
CR  - 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.
CR  - Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583. https://doi.org/10.1136/bmj.i6583
CR  - Panarese A, Shahini E. Letter: Covid-19, and vitamin D. Aliment Pharmacol Ther 2020;51:993–995. https://doi.org/10.1111/apt.15752
CR  - Oliver Z, Hafner S, Schmidt CQ. COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments. Naunyn Schmiedebergs Arch Pharmacol 2020;393:1131–1135. https://doi.org/10.1007/s00210-020- 01890-6
CR  - Epperly H, Vaughn FL, Mosholder AD, Maloney EM, Rubinson L. Nonsteroidal anti-inflammatory drug and aspirin use, and mortality among critically ill pandemic H1N1 influenza patients: an exploratory analysis. Jpn J Infect Dis 2016;69:248–251. https://doi.org/10.7883/yoken.jjid.2014.577
CR  - Amici C, Di Caro A, Ciucci A, Chiappa L, Castilletti C, Martella V, et al. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir Ther 2006;11:1021–1030. https://pubmed.ncbi.nlm.nih.gov/17302372/
CR  - 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:e21. https://doi.org/10.1016/s2213-2600 20 30116-8
CR  - Mark AM. Indomethacin and Resveratrol as Potential Treatment Adjuncts for SARS-CoV-2/COVID-19. Int J Clin Pract 2020;74:e13535. https://doi. org/10.1111/ijcp.13535
CR  - Research CfDEa. FDA advises patients on use of non-steroidal antiinflammatory drugs  NSAIDs  for COVID-19. FDA. https://www.fda. gov/drugs/drug-safety-and-availability/fda-advises-patients-use-nonsteroidal-anti-inflammatory-drugs-nsaids-covid-19#:~:text=for%20 COVID%2D19-,FDA%20advises%20patients%20on%20use%20of%20 non%2Dsteroidal%20anti%2Dinflammatory, NSAIDs %20for%20 COVID%2D19&text=%5B3%2F19%2F2020%5D,disease%20  COVID%2D19 .
CR  - Gomeni R, Xu T, Gao X, Bressolle-Gomeni F. Model based approach for estimating the dosage regimen of indomethacin a potential antiviral treatment of patients infected with SARS CoV-2. J Pharmacokinet Pharmacodyn 2020;47:189–198. https://doi.org/10.1007/s10928-020-09690-4
CR  - Marinella MA. Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV-2/COVID-19. Int J Clin Pract 2020;74:e13535. https://doi. org/10.1111/ijcp.13535
CR  - Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol 2020;92:2283–2285. https://doi.org/10.1002/ jmv.25948
CR  - Homolak J, Kodvanj I. Widely available lysosome targeting agents should be considered as a potential therapy for COVID-19. Int J Antimicrob Agents 2020;56:106044. https://doi.org/10.1016/j.ijantimicag.2020.106044
CR  - Sadiq NM, Robinson KJ, Terrell JM. Colchicine. In: Abai B, Abu-Ghosh A, Acharya AB, Acharya U, Adhia SG, Aeby TC, et al., editors. StatPearls. Treasure Island  FL : StatPearls Publishing; 2020.
CR  - Bilbul M, Paparone P, Kim AM, Mutalik S, Ernst CL. Psychopharmacology of COVID-19. Psychosomatics 2020;61:411–427. https://doi.org/10.1016/j. psym.2020.05.006
CR  - Toldo S, Abbate A. The NLRP3 inflammasome in acute myocardial infarction. Nature reviews. Cardiology 2018;15:203–214. https://doi.org/10.1038/ nrcardio.2017.161
CR  - Leung YY, Yao Hui LL, Kraus VB. Colchicine --Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45:341–350. https:// doi.org/10.1016/j.semarthrit.2015.06.013
CR  - Deftereos SG, Siasos G, Giannopoulos G, Vrachatis DA, Angelidis C, Giotaki SG, et al. The Greek study in the effects of colchicine in COvid-19 complications prevention  GRECCO-19 study : Rationale and study design. Hellenic J Cardiol 2020;61:42–45. https://doi.org/10.1016/j.hjc.2020.03.002
CR  - Nasiripour S, Zamani F, Farasatinasab M. Can Colchicine as an Old Anti-Inflammatory Agent Be Effective in COVID-19? J Clin Pharmacol 2020;60:828–829. https://doi.org/10.1002/jcph.1645
CR  - Cumhur Cure M, Kucuk A, Cure E. Colchicine may not be effective in COVID-19 infection; it may even be harmful? Clin Rheumatol 2020;39:2101– 2102. https://doi.org/10.1007/s10067-020-05144-x
CR  - Fragkou PC, Belhadi D, Peiffer-Smadja N, Moschopoulos CD, Lescure FX, Janocha H, et al. Review of trials currently testing treatment and prevention of COVID-19. Clin Microbiol Infect 2020;26:988–998. https://doi.org/10.1016/j. cmi.2020.05.019
CR  - Alessandri F, Pugliese F, Ranieri VM. The role of rescue therapies in the treatment of severe ARDS. Respir Care 2018;63:92–101. https://doi. org/10.4187/respcare.05752
CR  - Cherian SV, Kumar A, Akasapu K, Ashton RW, Aparnath M, Malhotra A. Salvage therapies for refractory hypoxemia in ARDS. Respir Med 2018;141:150–158. https://doi.org/10.1016/j.rmed.2018.06.030
CR  - Khan TA, Schnickel G, Ross D, Bastani S, Laks H, Esmailian F, et al. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg 2009;138:1417–1424. https://doi.org/10.1016/j.jtcvs.2009.04.063
CR  - Åkerström S, Mousavi-Jazi M, Klingström J, Leijon M, Lundkvist Å, Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol 2005;79:1966–1969. https://doi.org/10.1128/ jvi.79.3.1966-1969.2005
CR  - Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet  Lond Engl  1993;342:961–962. https://doi.org/10.1016/0140-6736 93 92004-d
CR  - Searcy RJ, Morales JR, Ferreira JA, Johnson DW. The role of inhaled prostacyclin in treating acute respiratory distress syndrome. Ther Adv Respir Dis 2015;9:302–312. https://doi.org/10.1177/1753465815599345
CR  - Medicine USNLo. U. S. National Library of Medicine. ClinicalTrials.gov; 2020. Apr 2. https://www.clinicaltrials.gov/ct2/search
CR  - Biospace. Mallinckrodt evaluates the potential role for inhaled nitric oxide to treat COVID-19 associated lung complications, engages with scientific, governmental and regulatory agencies. https://www.biospace.com/article/ releases/mallinckrodt-evaluates-the-potential-role-for-inhaled-nitric-oxide-totreat-covid-19-associated-lung-complications-engages-with-scientific-governmental-and-regulatory-agencies/
CR  - Pindiprolu SKSS, Pindiprolu SH. Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19. Med Hypotheses 2020;140:109765. https:// doi.org/10.1016/j.mehy.2020.109765
CR  - Chen W, Mook RA Jr, Premont RT, Wang J. Niclosamide: Beyond an antihelminthic drug. Cell Signal 2018;41:89–96. https://doi.org/10.1016/j.cellsig.2017.04.001
CR  - Wu CJ, Jan JT, Chen CM, Hsieh HP, Hwang DR, Liu HW, et al. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob Agents Chemother 2004;48:2693–2696. https://doi.org/10.1128/ aac.48.7.2693-2696.2004
CR  - Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res 2020;178:104787. https://doi.org/10.1016/j.antiviral.2020.104787
CR  - Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turkish J Med Sci 2020;50:611–619. https://doi.org/10.3906/sag-2004-145
CR  - Pepperrell T, Pilkington V, Owen A, Wang J, Hill AM. Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19. J Virus Erad 2020;6:52–60. https://doi.org/10.1016/S2055-6640 20 30017-0
CR  - Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health 2016;9:227–230. https://doi.org/10.1016/j.jiph.2016.04.001
CR  - Jasenosky LD, Cadena C, Mire CE, Borisevich V, Haridas V, Ranjbar S, et al. The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus. iScience 2019;19:1279–1290. https://doi. org/10.1016/j.isci.2019.07.003
CR  - Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844–847. https://doi.org/10.1111/jth.14768
CR  - Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18:1094–1099. https:// doi.org/10.1111/jth.14817
CR  - Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect 2020;53:436–443. https://doi. org/10.1016/j.jmii.2020.03.034
CR  - Seto B. Rapamycin and mTOR. a serendipitous discovery and implications for breast cancer. Clin Transl Med 2012;1:29. https://doi.org/10.1186/2001-1326- 1-29
CR  - Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, et al. Antiviral potential of ERK/MAPK and PI3K/AKT/ mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother 2015;59:1088–1099. https://doi.org/10.1128/aac.03659-14
CR  - Gupta N. Sirolimus treatment in hospitalized patients with covid-19 pneumonia. https://ClinicalTrials.gov/show/NCT04341675
CR  - Wang CH, Chung FT, Lin SM, Huang SY, Chou CL, Lee KY, et al. Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure. Crit Care Med 2014;42:313–321. https://doi.org/10.1097/ ccm.0b013e3182a2727d
CR  - Hui DSC. Adjunctive sirolimus and oseltamivir versus oseltamivir alone for treatment of influenza. https://ClinicalTrials.gov/show/NCT03901001
CR  - Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Networkbased drug repurposing for novel coronavirus 2019-nCoV/SARSCoV-2. Cell Discov 2020;6:14. https://doi.org/10.1038/s41421-020-0153-3
CR  - A medical records based study for the preliminary efficacy of Tocilizumab in the treatment of the patients with novel coronavirus pneumonia  COVID-19 . Chinese Clinical Trial Registry. http://www.chictr.org.cn/showprojen. aspx?proj=49409
CR  - Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020;18:164. https://doi.org/10.1186/s12967-020- 02339-3
CR  - Regeneron Pharmaceuticals. Evaluation of the efficacy and safety of sarilumab in hospitalized patients with COVID-19. https://www.clinicaltrials.gov/ct2/ show/NCT04315298
CR  - Cantini F, Niccoli L, Matarrese D, Nicastri E, Stobbione P, Goletti D. Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. J Infect 2020;81:318–356. https://doi.org/10.1016/j.jinf.2020.04.017
CR  - Bechman K, Subesinghe S, Norton S, Atzeni F, Galli M, Cope AP, et al. A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis. Rheumatology  Oxford  2019;58:1755– 1766. https://doi.org/10.1093/rheumatology/kez087
CR  - 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:e30–e31. https://doi.org/10.1016/S0140-6736 20 30304-4
CR  - Monteagudo LA, Boothby A, Gertner E. Continuous intravenous anakinra infusion to calm the cytokine storm in macrophage activation syndrome. ACR Open Rheumatol 2020;2:276–282. https://doi.org/10.1002/acr2.11135
CR  - Sönmez HE, Demir S, Bilginer Y, Özen S. Anakinra treatment in macrophage activation syndrome: a single center experience and systemic review of literature. Clin Rheumatol 2018;37:3329–3335. https://doi.org/10.1007/ s10067-018-4095-1
CR  - Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev 2018;281:8–27. https://doi.org/10.1111/imr.12621
CR  - Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflmmation: a retrospective cohort study. Lancet Rheumatol 2020;2:e325–e331. https://doi.org/10.1016/ S2665-9913 20 30127-2
CR  - King A, Vail A, O’Leary C, Hannan C, Brough D, Patel H, et al. Anakinra in COVID-19: important considerations for clinical trials. Lancet Rheumatol 2020;2:e379–e381. https://doi.org/10.1016/S2665-9913 20 30160-0
CR  - Kajiwara C, Kusaka Y, Kimura S, Yamaguchi T, Nanjo Y, Ishii Y, et al. Metformin mediates protection against Legionella pneumonia through activation of AMPK and mitochondrial reactive oxygen species. J Immunol 2018;200:623–631. https://doi.org/10.4049/jimmunol.1700474
CR  - Zhang M, He JQ. Impacts of metformin on tuberculosis incidence and clinical outcomes in patients with diabetes: a systematic review and meta-analysis. Eur J Clin Pharmacol 2020;76:149–159. https://doi.org/10.1007/s00228-019-02786-y
CR  - Mendy A, Gopal R, Alcorn JF, Forno E. Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin. Respirology 2019;24:646–651. https://doi.org/10.1111/resp.13486
CR  - Ho T, Huang C, Tsai Y, Lien ASY, Lai F, Yu CJ. Metformin use mitigates the adverse prognostic effect of diabetes mellitus in chronic obstructive pulmonary disease. Respir Res 2019;20:69. https://doi.org/10.1186/s12931-019-1035-9
CR  - Arnold R, Neumann M, König W. Peroxisome proliferatoractivated receptorgamma agonists inhibit respiratory syncytial virus-induced expression of intercellular adhesion molecule-1 in human lung epithelial cells. Immunology 2007;121:71–81. https://doi.org/10.1111/j.1365-2567.2006.02539.x
CR  - Bauer CM, Zavitz CC, Botelho FM, Lambert KN, Brown EG, Mossman KL, et al. Treating viral exacerbations of chronic obstructive pulmonary disease: insights from a mouse model of cigarette smoke and H1N1 influenza infection. PLoS One 2010;5:e13251. https://doi.org/10.1371/journal.pone.0013251
CR  - Zhang W, Xu YZ, Liu B, Wu R, Yang YY, Xiao XQ, et al. Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis. ScientificWorldJournal 2014;2014:603409. https://doi.org/10.1155/2014/603409
CR  - Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol 2020;92:479–490. https://doi.org/10.1002/ jmv.25707
CR  - Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn 2+  inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 2010;6:e1001176. https://doi.org/10.1371/journal.ppat.1001176
CR  - Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS‑CoV, MERS‑CoV, and 2019‑nCoV. J Med Virol 2020;92:491–494. https://doi.org/10.1002/jmv.25709
CR  - Xue J, Moyer A, Peng B, Wu J, Hannafon, Ding WQ, et al. Chloroquine is a zinc ionophore. PLoS One 2014;9:e109180. https://doi.org/10.1371/journal. pone.0109180
CR  - Guastalegname M, Vallone A. Could chloroquine/hydroxychloroquine be harmful in Coronavirus disease 2019  COVID‑19  treatment? Clin Infect Dis 2020;71:888–889. https://doi.org/10.1093/cid/ciaa321
CR  - Dabbagh‑Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O’Sullivan CK, Fernández-Larrea JB. Zinc ionophore activity of quercetin and epigallocatechin‑gallate: From Hepa 1-6 cells to a liposome model. J Agric Food Chem 2014;62:8085–8093. https://doi.org/10.1021/jf5014633
CR  - Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, et al. Disulfiram can inhibit MERS and SARS coronavirus papain‑like proteases via different modes. Antiviral Res 2018;150:155–163. https://doi.org/10.1016/j. antiviral.2017.12.015
CR  - Sargsyan K, Chen T, Grauffel C, Lim C. Identifying COVID‑19 drug‑sites susceptible to clinically safe Zn‑ejector drugs using evolutionary/physical principles. OSF Preprints 2020. https://doi.org/10.31219/osf.io/snuqf
CR  - Xu L, Tong J, Wu Y, Zhao S, Lin BL. Targeted oxidation strategy  TOS  for potential inhibition of Coronaviruses by disulfiram –a 70‑year-old anti‑alcoholism drug. ChemRxiv 2020. https://chemrxiv.org/articles/ preprint/Targeted_Oxidation_Strategy_TOS_for_Potential_Inhibition_ of_Coronaviruses_by_Disulfiram_a_70-Year_Old_Anti-Alcoholism_ Drug/11936292
CR  - Hoffmann M, Kleine‑Weber H, Krüger N, Mueller MA, Drosten C, Pöhlmann S. The novel coronavirus 2019  2019-nCoV  uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv 2020. https://doi.org/10.1101/2020.01.31.929042
CR  - Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin‑converting enzyme 2 ACE2  as a SARS‑C oV‑2 receptor: Molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586–590. https://doi. org/10.1007/s00134-020-05985-9
CR  - Speth R, Carrera E, Jean‑Baptiste M, Joachim A, Linares A. Concentration‑dependent effects of zinc on angiotensin‑converting enzyme‑2 activity  1067.4 . FASEB J 2014;28:1067.4. https://doi.org/10.1096/ fasebj.28.1_supplement.1067.4
CR  - Chilvers MA, McKean M, Rutman A, Myint BS, Silverman M, O’Callaghan C. The effects of coronavirus on human nasal ciliated respiratory epithelium. Eur Respir J 2001;18:965–970. https://doi.org/10.1183/09031936.01.00093001
CR  - Maret W. Analyzing free zinc  II  ion concentrations in cell biology with fluorescent chelating molecules. Metallomics 2015;7:202–211. https://doi. org/10.1039/c4mt00230j
CR  - Essaidi‑Laziosi M, Brito F, Benaoudia S, Royston L, Cagno V, FernandesRocha M, et al. Propagation of respiratory viruses in human airway epithelia reveals persistent virus‑specific signatures. J Allergy Clin Immunol 2018;141:2074–2084. https://doi.org/10.1016/j.jaci.2017.07.018
CR  - Pittet LA, Hall‑Stoodley L, Rutkowski MR, Harmsen AG. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae. Am J Respir Cell Mol Biol 2010;42:450–460. https://doi.org/10.1165/rcmb.2007-0417oc
CR  - Darma A, Athiyyah AF, Ranuh RG, Merbawani W, Setyoningrum RA, Hidajat B, et al. Zinc supplementation effect on the bronchial cilia length, the number of cilia, and the number of intact bronchial cell in zinc deficiency rats. Indones Biomed J 2020;12:78–84. https://doi.org/10.18585/inabj.v12i1.998
CR  - Woodworth BA, Zhang S, Tamashiro E, Bhargave G, Palmer JN, Cohen NA. Zinc increases ciliary beat frequency in a calcium‑dependent manner. Am J Rhinol Allergy 2010;24:6–10. https://doi.org/10.2500/ajra.2010.24.3379
CR  - Truong‑Tran AQ, Carter J, Ruffin R, Zalewski PD. New insights into the role of zinc in the respiratory epithelium. Immunol Cell Biol 2001;79:170–177. https://doi.org/10.1046/j.1440-1711.2001.00986.x
CR  - Roscioli E, Jersmann HP, Lester S, Badiei A, Fon A, Zalewski P, et al. Zinc deficiency as a codeterminant for airway epithelial barrier dysfunction in an ex vivo model of COPD. Int J Chron Obstruct Pulmon Dis 2017;12:3503–3510. https://doi.org/10.2147/copd.s149589
CR  - Wittekindt OH. Tight junctions in pulmonary epithelia during lung inflammation. Pflugers Arch 2017;469:135–147. https://doi.org/10.1007/ s00424-016-1917-3
CR  - Günzel D, Yu ASL. Claudins and the modulation of tight junction permeability. Physiol Rev 2013;93:525–569. https://doi.org/10.1152/physrev.00019.2012
CR  - Golchin A, Farahany TZ. Biological products: cellular therapy and FDA approved products. Stem Cell Rev Rep 2019;15:166–175. https://doi. org/10.1007/s12015-018-9866-1
CR  - Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis 2020;11:216–228. https://doi.org/10.14336/ ad.2020.0228
CR  - Liang B, Chen J, Li T, Wu H, Yang W, Li Y, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells. ChinaXiv 2020. http://chinaxiv.org/abs/202002.00084
CR  - Li Z, Niu S, Guo B, Gao T, Wang L, Wang Y, et al. Stem cell therapy for COVID-19, ARDS and pulmonary fibrosis. Cell Prolif 2020;53:e12939. https://doi.org/10.1111/cpr.12939
CR  - Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front Immunol 2020;11:1708. https://doi.org/10.3389/fimmu.2020.01708
CR  - Glenn JD, Whartenby KA. Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World J Stem Cells 2014;6:526–539. https:// doi.org/10.4252/wjsc.v6.i5.526
CR  - Xiao K, Hou F, Huang X, Li B, Qian ZR, Xie L. Mesenchymal stem cells: current clinical progress in ARDS and COVID-19. Stem Cell Res Ther 2020;11:305. https://doi.org/10.1186/s13287-020-01804-6
CR  - Al-Khawaga S, Abdelalim EM. Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients. Stem Cell Res Ther 2020;11. https://doi.org/10.1186/ s13287-020-01963-6
CR  - Golchin A, Seyedjafari E, Ardeshirylajimi A. Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev Rep 2020;16:427–433. https://doi.org/10.1007/s12015-020-09973-w
CR  - Cutino-Moguel MT, Eades C, Rezvani K, Armstrong-James D. Immunotherapy for infectious diseases in haematological immunocompromise. Br J Haematol 2017;177:348–356. https://doi.org/10.1111/bjh.14595
CR  - Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV. Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: rationale and mechanisms of action. Nat Clin Pract Rheumatol 2007;3:262– 272. https://doi.org/10.1038/ncprheum0481
CR  - Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19  COVID-19 . Asian Pac J Allergy Immunol 2020;38:10–18. https://doi.org/10.12932/AP-200220-0773
CR  - Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013;495:251–254. https://doi.org/10.1038/nature12005
CR  - Du L, Yang Y, Zhou Y, Lu L, Li F, Jiang S. MERS-CoV spike protein: a key target for antivirals. Expert Opin Ther Targets 2017;21:131–143. https://doi.or g/10.1080/14728222.2017.1271415
CR  - Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensinconverting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003;426:450–454. https://doi.org/10.1038/nature02145
CR  - Coughlin MM, Prabhakar BS. Neutralizing human monoclonal antibodies to Severe acute respiratory syndrome coronavirus: target, mechanism of action and therapeutic potential. Rev Med Virol 2012;22:2–17. https://doi. org/10.1002/rmv.706
CR  - Baum A, Ajithdoss D, Copin R, Zhou A, Lanza K, Negron N, et al. REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 2020;370:1110–1115. https://doi.org/10.1126/science.abe2402
CR  - Regeneron. REGN-COV2 Antibody Cocktail Reduced Viral Levels and Improved Symptoms in Non-Hospitalized COVID-19 Patients. Regeneron 2020. https://investor.regeneron.com/news-releases/news-release-details/ regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and/
CR  - Jahanshahlu L, Rezaei N. Monoclonal antibody as a potential anti-COVID-19. Biomed Pharmacother 2020;129:110337. https://doi.org/10.1016/j. biopha.2020.110337
UR  - https://doi.org/10.51261/yiu.2021.00018
L1  - https://dergipark.org.tr/tr/download/article-file/3782959
ER  -