Overview of Immune Perspectives and Current Treatment Strategies against COVID-19
Abstract
Abstract Views: 364COVID-19 is a highly infectious respiratory disorder, affecting millions with about 10% fatality rate. Infected patients may be symptomatic and show mild to severe symptoms, manifesting as mild fever, cough, headache, and nausea or they may remain asymptomatic, showing no symptoms at all. World Health Organization (WHO) reported over 260, 493 573confirmed cases worldwide with 5 195, 354deaths (November 2021). There are myriads of promising approaches to pharmacologically treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the newly reported seventh human coronavirus responsible for the COVID-19 pandemic. There are various types of potential drugs, such as monoclonal antibodies, interferon therapies, peptides, small molecule drugs, oligonucleotides, and vaccines, under consideration to target various structural components of the virus. This study focused on reviewing potential drug candidates, namely remdesivir, lopinavir, emetine, aloxistatin, viracept, homoharringtonine, ivermectin, favipiravir, tocilizumab, chloroquine, and leronlimab that can be used to treat COVID-19 infection. These drugs target the membrane nucleocapsid, spike, or envelope proteins, and are either in clinical trials or are under consideration. These drugs directly inhibit the viral infection, while others trigger the immune system to fight against the virus. We also overviewed the immunization ability of in-use and accepted vaccines, such as Pfizer and Moderna. It was followed by a review of research dealing with the immune system and how it tries to manage the infection as well as vaccines and potential therapeutic agents.
Keywords: adaptive immune response, COVID-19, innate immune response, SARS-CoV-2, therapeutic drugs, vaccine
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References
[2] C. Huang et al., “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China,” Lancet, 2020, doi: 10.1016/S0140-6736(20)30183-5.
[3] N. Lee et al., “A major outbreak of severe acute respiratory syndrome in Hong Kong,” N. Engl. J. Med., 2003, doi: 10.1056/NEJMoa030685.
[4] World Health Organization, “Laboratory testing of 2019 novel coronavirus (2019-nCoV) in suspected human cases: interim guidance, 17 January 2020,” WHO - Interim Guid., 2020.
[5] M. L. Holshue et al., “First case of 2019 novel coronavirus in the United States,” N. Engl. J. Med., 2020, doi: 10.1056/NEJMoa2001191.
[6] M. A. Shereen, S. Khan, A. Kazmi, N. Bashir, and R. Siddique, “COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses,” Journal of Advanced Research. 2020, doi: 10.1016/j.jare.2020.03.005.
[7] L. Chang, Y. Yan, and L. Wang, “Coronavirus Disease 2019: Coronaviruses and Blood Safety,” Transfusion Medicine Reviews. 2020, doi: 10.1016/j.tmrv.2020.02.003.
[8] W. H. Organization, “Weekly Operational Update on COVID-19, 10 November 2020,” 2020.
[9] W. Guan et al., “Clinical characteristics of coronavirus disease 2019 in China,” N. Engl. J. Med., 2020, doi: 10.1056/NEJMoa2002032.
[10] C. A. Donnelly et al., “Epidemiological and genetic analysis of severe acute respiratory syndrome,” Lancet Infectious Diseases. 2004, doi: 10.1016/S1473-3099(04)01173-9.
[11] S. Felsenstein, J. A. Herbert, P. S. McNamara, and C. M. Hedrich, “COVID-19: Immunology and treatment options,” Clinical Immunology. 2020, doi: 10.1016/j.clim.2020.108448.
[12] J. jin Zhang et al., “Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China,” Allergy Eur. J. Allergy Clin. Immunol., 2020, doi: 10.1111/all.14238.
[13] X. Jiang, S. Rayner, and M. H. Luo, “Does SARS-CoV-2 has a longer incubation period than SARS and MERS?,” Journal of Medical Virology. 2020, doi: 10.1002/jmv.25708.
[14] Q. Ruan, K. Yang, W. Wang, L. Jiang, and J. Song, “Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China,” Intensive Care Medicine. 2020, doi: 10.1007/s00134-020-05991-x.
[15] Y. Wang, Y. Wang, Y. Chen, and Q. Qin, “Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures,” Journal of Medical Virology. 2020, doi: 10.1002/jmv.25748.
[16] S. A. Hassan, F. N. Sheikh, S. Jamal, J. K. Ezeh, and A. Akhtar, “Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment,” Cureus, 2020, doi: 10.7759/cureus.7355.
[17] C. Qin et al., “Dysregulation of Immune Response in Patients With Coronavirus 2019 ( COVID-19 ) in Wuhan , China,” vol. 2019, no. Xx Xxxx, pp. 4–10, 2020, doi: 10.1093/cid/ciaa248.
[18] C.-K. Min et al., “Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity,” Sci. Rep., vol. 6, no. 1, p. 25359, 2016, doi: 10.1038/srep25359.
[19] D. Wang et al., “Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China,” Jama, vol. 323, no. 11, pp. 1061–1069, 2020.
[20] N. Vabret et al., “Immunology of COVID-19: Current State of the Science,” Immunity. 2020, doi: 10.1016/j.immuni.2020.05.002.
[21] Y. Zhou et al., “Clinical and Autoimmune Characteristics of Severe and Critical Cases with COVID-19,” Clinical and Translational Science. 2020, doi: 10.1111/cts.12805.
[22] Y. Chen, Q. Liu, and D. Guo, “Emerging coronaviruses: Genome structure, replication, and pathogenesis,” Journal of Medical Virology. 2020, doi: 10.1002/jmv.25681.
[23] P. Zhou et al., “A pneumonia outbreak associated with a new coronavirus of probable bat origin,” Nature, 2020, doi: 10.1038/s41586-020-2012-7.
[24] N. Zhu et al., “A novel coronavirus from patients with pneumonia in China, 2019,” N. Engl. J. Med., 2020, doi: 10.1056/NEJMoa2001017.
[25] M. L. DeDiego et al., “A Severe Acute Respiratory Syndrome Coronavirus That Lacks the E Gene Is Attenuated In Vitro and In Vivo,” J. Virol., 2007, doi: 10.1128/jvi.01467-06.
[26] S. Hussain et al., “Identification of Novel Subgenomic RNAs and Noncanonical Transcription Initiation Signals of Severe Acute Respiratory Syndrome Coronavirus,” J. Virol., 2005, doi: 10.1128/jvi.79.9.5288-5295.2005.
[27] L. Ni et al., “Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2,” medRxiv, p. 2020.03.17.20036640, 2020, doi: 10.1101/2020.03.17.20036640.
[28] E. Prompetchara, C. Ketloy, and T. Palaga, “Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic,” Asian Pacific Journal of Allergy and Immunology. 2020, doi: 10.12932/AP-200220-0772.
[29] S. Akira, S. Uematsu, and O. Takeuchi, “Pathogen recognition and innate immunity,” Cell. 2006, doi: 10.1016/j.cell.2006.02.015.
[30] R. Baccala et al., “Sensors of the innate immune system: Their mode of action,” Nature Reviews Rheumatology. 2009, doi: 10.1038/nrrheum.2009.136.
[31] E. De Wit, N. Van Doremalen, D. Falzarano, and V. J. Munster, “SARS and MERS: Recent insights into emerging coronaviruses,” Nature Reviews Microbiology. 2016, doi: 10.1038/nrmicro.2016.81.
[32] L. B. Ivashkiv and L. T. Donlin, “Regulation of type i interferon responses,” Nature Reviews Immunology. 2014, doi: 10.1038/nri3581.
[33] D. Blanco-Melo et al., “Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19,” Cell, 2020, doi: 10.1016/j.cell.2020.04.026.
[34] L. D’Antiga, “Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic,” Liver Transplantation. 2020, doi: 10.1002/lt.25756.
[35] T. E. Cecere, S. M. Todd, and T. LeRoith, “Regulatory T cells in arterivirus and coronavirus infections: Do they protect against disease or enhance it?,” Viruses. 2012, doi: 10.3390/v4050833.
[36] Q. Maloir, K. Ghysen, C. von Frenckell, R. Louis, and J. Guiot, “[Acute respiratory distress revealing antisynthetase syndrome].,” Rev. Med. Liege, 2018.
[37] S. Kumar, R. Nyodu, V. K. Maurya, and S. K. Saxena, “Host Immune Response and Immunobiology of Human SARS-CoV-2 Infection,” in Coronavirus Disease 2019 (COVID-19), Springer, 2020, pp. 43–53.
[38] S.-Y. Fung, K.-S. Yuen, Z.-W. Ye, C.-P. Chan, and D.-Y. Jin, “A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses,” Emerg. Microbes Infect., vol. 9, no. 1, pp. 558–570, 2020.
[39] P. Ahmadpoor and L. Rostaing, “Why the immune system fails to mount an adaptive immune response to a COVID-19 infection,” Transplant International. 2020, doi: 10.1111/tri.13611.
[40] C.-F. Rate, “Characteristics of Patients Dying in Relation to COVID-19 in Italy Onder G, Rezza G, Brusaferro S,” JAMA. Publ. online March, vol. 23, 2020.
[41] W. Liu et al., “Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome,” J. Infect. Dis., vol. 193, no. 6, pp. 792–795, 2006.
[42] W. J. Liu et al., “T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV,” Antiviral Res., vol. 137, pp. 82–92, 2017.
[43] L. Ni et al., “Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals,” Immunity, 2020.
[44] H.-S. Shin et al., “Immune responses to Middle East respiratory syndrome coronavirus during the acute and convalescent phases of human infection,” Clin. Infect. Dis., vol. 68, no. 6, pp. 984–992, 2019.
[45] E. Prompetchara et al., “DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice,” PLoS One, vol. 16, no. 3 March, pp. 1–16, 2021, doi: 10.1371/journal.pone.0248007.
[46] Y. Zhang, S. Gargan, Y. Lu, and N. J. Stevenson, “An overview of current knowledge of deadly covs and their interface with innate immunity,” Viruses, vol. 13, no. 4, 2021, doi: 10.3390/v13040560.
[47] J. L. Santarpia et al., “Aerosol and surface contamination of SARS-CoV-2 observed in quarantine and isolation care,” Sci. Rep., vol. 10, no. 1, pp. 1–8, 2020.
[48] Y. Yang et al., “The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China,” J. Autoimmun., p. 102434, 2020.
[49] T. P. Sheahan et al., “Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV,” Nat. Commun., vol. 11, no. 1, pp. 1–14, 2020.
[50] C. Barton et al., “Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models,” Antimicrob. Agents Chemother., vol. 58, no. 1, pp. 120–127, 2014.
[51] Y. Ma-Lauer, Y. Zheng, M. Malešević, B. von Brunn, G. Fischer, and A. von Brunn, “Influences of cyclosporin A and non-immunosuppressive derivatives on cellular cyclophilins and viral nucleocapsid protein during human coronavirus 229E replication,” Antiviral Res., vol. 173, p. 104620, 2020.
[52] S. Goodbourn, L. Didcock, and R. E. Randall, “Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures,” J. Gen. Virol., vol. 81, no. 10, pp. 2341–2364, 2000.
[53] S. Khan et al., “Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options,” J. Clin. Microbiol., vol. 58, no. 5, 2020.
[54] A. L. Totura and S. Bavari, “Broad-spectrum coronavirus antiviral drug discovery,” Expert Opin. Drug Discov., vol. 14, no. 4, pp. 397–412, 2019, doi: 10.1080/17460441.2019.1581171.
[55] A. J. Brown et al., “Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase,” Antiviral Res., 2019, doi: 10.1016/j.antiviral.2019.104541.
[56] E. de Wit et al., “Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection,” Proc. Natl. Acad. Sci., vol. 117, no. 12, pp. 6771–6776, 2020.
[57] M. L. Agostini et al., “Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease,” MBio, vol. 9, no. 2, 2018.
[58] K.-T. Choy et al., “Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro,” Antiviral Res., p. 104786, 2020.
[59] C.-W. Yang et al., “Repurposing old drugs as antiviral agents for coronaviruses,” Biomed. J., 2020.
[60] P. I. Andersen et al., “Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine,” Viruses, vol. 11, no. 10, p. 964, 2019.
[61] A. L. C. Valadão et al., “Natural plant alkaloid (emetine) inhibits HIV-1 replication by interfering with reverse transcriptase activity,” Molecules, vol. 20, no. 6, pp. 11474–11489, 2015.
[62] N. Khandelwal et al., “Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants,” Antiviral Res., vol. 144, pp. 196–204, 2017.
[63] R. Mukhopadhyay et al., “Efficacy and mechanism of action of low dose emetine against human cytomegalovirus,” PLoS Pathog., vol. 12, no. 6, 2016.
[64] R. Lu et al., “Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” Lancet, vol. 395, no. 10224, pp. 565–574, 2020.
[65] L. Shen et al., “High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses,” J. Virol., vol. 93, no. 12, pp. e00023-19, 2019.
[66] H.-J. Dong et al., “The natural compound homoharringtonine presents broad antiviral activity in vitro and in vivo,” Viruses, vol. 10, no. 11, p. 601, 2018.
[67] A. Quintás‐Cardama, H. Kantarjian, and J. Cortes, “Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009,” Cancer, vol. 115, no. 23, pp. 5382–5393, 2009.
[68] I.-6 R. M. R. A. (IL6R M. Consortium, “The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis,” Lancet, vol. 379, no. 9822, pp. 1214–1224, 2012.
[69] C. Kotch, D. Barrett, and D. T. Teachey, “Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome,” Expert Rev. Clin. Immunol., vol. 15, no. 8, pp. 813–822, 2019.
[70] P. Luo, Y. Liu, L. Qiu, X. Liu, D. Liu, and J. Li, “Tocilizumab treatment in COVID‐19: A single center experience,” J. Med. Virol., 2020.
[71] G. Guaraldi et al., “Tocilizumab in patients with severe COVID-19: a retrospective cohort study,” Lancet Rheumatol., 2020.
[72] M. Hussain, S. Zaman, and A. Bari, “Guidelines for the Treatment of Severe and Critical Cases of COVID-19,” 2020.
[73] J. Radbel, N. Narayanan, and P. J. Bhatt, “Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report,” Chest, 2020.
[74] Y. Yan et al., “Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model,” Cell Res., vol. 23, no. 2, pp. 300–302, 2013.
[75] M. J. Vincent, E. Bergeron, S. Benjannet, B. R. Erickson, P. E. Rollin, and T. G. Ksiazek, “Virol,” Chloroquine is a potent Inhib. SARS coronavirus Infect. spread J, vol. 2, p. 69, 2005.
[76] M. Wang et al., “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,” Cell Res., vol. 30, no. 3, pp. 269–271, 2020.
[77] Z. Sahraei, M. Shabani, S. Shokouhi, and A. Saffaei, “Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine,” Int J Antimicrob Agents, vol. 105945, no. 10.1016, 2020.
[78] F. Touret and X. de Lamballerie, “Of chloroquine and COVID-19,” Antiviral Res., p. 104762, 2020.
[79] S. Sciascia et al., “Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in severe patients with COVID-19,” Clin Exp Rheumatol, vol. 38, no. 3, pp. 529–532, 2020.
[80] S. Bobdey, S. K. Kaushik, and A. S. Menon, “The conundrum of two-dose interval of ChAdOx1 nCOV-19 corona virus vaccine : Way ahead,” no. January, 2020.
[81] M. D. Shin et al., “COVID-19 vaccine development and a potential nanomaterial path forward,” Nat. Nanotechnol., vol. 15, no. 8, pp. 646–655, 2020, doi: 10.1038/s41565-020-0737-y.
[82] R. A. Rather, T. Islam, I. U. L. Rehman, and D. Pandey, “Development of Vaccine Against Coronavirus Disease 2019 ( Covid-19 ) in India,” Asian J. Adv. Med. Sci., vol. 3, no. 2, pp. 13–21, 2021.
[83] M. W. Tenforde et al., “Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥ 65 Years —January-March 2021,” Mmwr, vol. 70, no. 18, pp. 674–679, 2021.
[84] J. L. Bernal et al., “Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study,” BMJ, vol. 373, 2021, doi: 10.1136/bmj.n1088.
[85] C. Chuaychoosakoon, W. Parinyakhup, P. Tanutit, and K. Maliwankul, “Shoulder injury related to Sinovac COVID-19 vaccine : A case report,” Ann. Med. Surg., vol. 68, no. July, p. 102622, 2021, doi: 10.1016/j.amsu.2021.102622.
[86] F. Amanat and F. Krammer, “SARS-CoV-2 vaccines: status report,” Immunity, 2020.
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