journal article·2021-08-13Open access

SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy

Gianmarco Marcianò, Roberta Roberti, Caterina Palleria, Davida Mirra, Vincenzo Rania, Alessandro Casarella, Giovambattista De Sarro, Luca Gallelli

Applied Sciences· Volume 11· Issue 16

Abstract

One year on from the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine has made several steps towards increasing the therapeutic options against its treatment. Despite the lack of specific therapies, international societies have introduced new guidelines and launched several trials to test the efficacy of new protocols and drugs. Drug repurposing has been a fundamental strategy to find quick ways to fight the pathogen, even if it is new compounds that are drawing the attention of the scientific community. Tailored therapy should be considered to be a milestone in treatment in order to increase drug efficacy and to reduce drug toxicity. Therefore, both drug characteristics (i.e., pharmacokinetic, pharmacodynamic and safety) and the patient characteristics (i.e., stage of disease, comorbidity, concomitant treatments and the mutation of single nucleotides) could represent the key to achieving this objective. In the present study we performed a narrative review of the pharmacological treatment used to date in the management of coronavirus disease 2019 (COVID-19).
Source: crossref · Quality: baseline

Research context

OpenAlex topics: SARS-CoV-2 and COVID-19 Research · COVID-19 Clinical Research Studies · Pharmacological Receptor Mechanisms and Effects

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Operative Unit of Pharmacology and Pharmacovigilance, “Mater Domini” Hospital, 88100 Catanzaro, Italy

Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy

Research Center FAS@UMG, Department of Health Science, University Magna Graecia, 88100 Catanzaro, Italy

References (100+)

Show source-provided references
1. COVID-19: Progress in diagnostics, therapy and vaccination10.7150/thno.47987 ↗
2. COVID-19: A review of therapeutic strategies and vaccine candidates10.1016/j.clim.2020.108634 ↗
3. Extrapulmonary manifestations of COVID-1910.1038/s41591-020-0968-3 ↗
4. NIH (2021, August 12). Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https://covid19treatmentguidelines.nih.gov/.
5. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal10.1016/j.healun.2020.03.012 ↗
6. (2021, August 12). ClinicalTrials.gov, Available online: https://clinicaltrials.gov/ct2/who_table.
7. Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis10.1007/s00296-019-04332-6 ↗
8. Characteristics and clinical implications of the pharmacokinetic profile of ibuprofen in patients with knee osteoarthritis10.1007/s40261-012-0011-7 ↗
9. Retrospective evaluation of adverse drug reactions induced by nonsteroidal anti-inflammatory drugs10.2165/00044011-200727020-00004 ↗
10. Emerging treatment strategies for COVID-19 infection10.1007/s10238-020-00671-y ↗
11. Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-1910.1016/j.jbior.2021.100818 ↗
12. Cardiovascular Complications of COVID-19: Pharmacotherapy Perspective10.1007/s10557-020-07037-2 ↗
13. European Medicines Agency (2021, August 12). Summary of Product Characteristics-Veklury. Available online: https://www.ema.europa.eu/en/documents/product-information/veklury-epar-product-information_en.pdf.
14. Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-1910.1002/phar.2429 ↗
15. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: A randomized clinical trial10.1001/jama.2021.0202 ↗
16. (2021, August 12). European Medicines Agency Olumiant-Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf.
17. Baricitinib plus Remdesivir for Hospitalized Adults with COVID-1910.1056/NEJMoa2031994 ↗
18. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with COVID-1910.1056/NEJMoa2035002 ↗
19. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial10.1016/j.ijantimicag.2020.105949 ↗
20. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate COVID-1910.1056/NEJMoa2019014 ↗
21. Corticosteroids—Mechanisms of action in health and disease10.1016/j.rdc.2015.08.002 ↗
22. RECOVERY Collaborative Group (2021). Dexamethasone in Hospitalized Patients with COVID-19. N. Engl. J. Med., 384, 693–704.10.1056/NEJMoa2021436 ↗
23. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review
24. Role of Favipiravir in the Treatment of COVID-1910.1016/j.ijid.2020.10.069 ↗
25. Use of Ivermectin Is Associated with Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study10.1016/j.chest.2020.10.009 ↗
26. Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE210.21873/invivo.12134 ↗
27. Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients
28. European Medicines Agency (2021, August 12). Kaletra-Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/documents/product-information/kaletra-epar-product-information_en.pdf.
29. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe COVID-1910.1056/NEJMoa2001282 ↗
30. Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial10.1016/S0140-6736(20)32013-4 ↗
31. (2021). Repurposed Antiviral Drugs for COVID-19—Interim WHO Solidarity Trial Results. N. Engl. J. Med., 384, 497–511.10.1056/NEJMoa2023184 ↗
32. Compassionate Use of Remdesivir for Patients with Severe COVID-1910.1056/NEJMoa2007016 ↗
33. Remdesivir for the Treatment of COVID-19—Final Report10.1056/NEJMoa2007764 ↗
34. Burwick, R.M., Yawetz, S., Stephenson, K.E., Collier, A.-R.Y., Sen, P., Blackburn, B.G., Kojic, E.M., Hirshberg, A., Suarez, J.F., and Sobieszczyk, M.E. (2020). Compassionate Use of Remdesivir in Pregnant Women with Severe Coronavirus Disease 2019. Clin. Infect. Dis., 1–9.10.1093/cid/ciaa1466 ↗
35. Tocilizumab in Patients Hospitalized with COVID-19 Pneumonia10.1056/NEJMoa2030340 ↗
36. (2021). RECOVERY Collaborative Group Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet, 397, 1637–1645.
37. REMAP-CAP Investigators (2021). Interleukin-6 Receptor Antagonists in Critically Ill Patients with COVID-19. N. Engl. J. Med., 384, 1491–1502.10.1056/NEJMoa2100433 ↗
38. Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment10.1007/s40268-020-00333-0 ↗
39. (2021, August 12). AIFA Riassunto delle Caratteristiche del Prodotto—Soldesam. Available online: https://sci-hub.ren/10.1017/S1121189X00010320.
40. Association of Polymorphisms of Cytochrome P450 2D6 with Blood Hydroxychloroquine Levels in Patients with Systemic Lupus Erythematosus10.1002/art.39402 ↗
41. Browning, D.J. (2014). Hydroxychloroquine and Chloroquine Retinopathy, Springer.10.1007/978-1-4939-0597-3 ↗
42. European Medicines Agency (2021, August 12). Neofordex—Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/documents/product-information/neofordex-epar-product-information_en.pdf.
43. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection10.1002/cpt.1844 ↗
44. The pharmacokinetics and interactions of ivermectin in humans—A mini-review10.1208/s12248-007-9000-9 ↗
45. Population pharmacokinetics of oral ivermectin in venous plasma and dried blood spots in healthy volunteers10.1111/bcp.13840 ↗
46. (2021, August 12). AIFA Riassunto delle caratteristiche del prodotto-Ivermectina, Available online: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_007073_043463_RCP.pdf&sys=m0b1l3.
47. LopinavirRitonavir: A review of its use in the management of HIV-1 infection10.2165/11204950-000000000-00000 ↗
48. European Medicines Agency (2021). Summary of Product Charcateristics—RoActemra, European Medicines Agency.
49. A valid warning or clinical lore: An evaluation of safety outcomes of remdesivir in patients with impaired renal function from a multicenter matched cohort
50. Pettit, N.N., Pisano, J., Nguyen, C.T., Lew, A.K., Hazra, A., Sherer, R., and Mullane, K. (2020). Remdesivir Use in the Setting of Severe Renal Impairment: A Theoretical Concern or Real Risk?. Clin. Infect. Dis., ciaa1851.10.1093/cid/ciaa1851 ↗
51. Drug interactions: A review of the unseen danger of experimental COVID-19 therapies10.1093/jac/dkaa340 ↗
52. Olender, S.A., Walunas, T.L., Martinez, E., Perez, K.K., Castagna, A., Wang, S., Kurbegov, D., Goyal, P., Ripamonti, D., and Balani, B. (2021). Remdesivir versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality. Open Forum Infect. Dis., 1–9.10.1093/ofid/ofab278 ↗
53. Olender, S.A., Perez, K.K., Go, A.S., Balani, B., Price-Haywood, E.G., Shah, N.S., Wang, S., Walunas, T.L., Swaminathan, S., and Slim, J. (2020). Remdesivir for Severe COVID-19 versus a Cohort Receiving Standard of Care. Clin. Infect. Dis., ciaa1041.10.1093/cid/ciaa1041 ↗
54. COVID-19: Discovery, diagnostics and drug development10.1016/j.jhep.2020.09.031 ↗
55. Effects of chloroquine on viral infections: An old drug against today’s diseases?10.1016/S1473-3099(03)00806-5 ↗
56. (2021, August 12). AIFA Riassunto Delle Carattetistiche del Prodotto-Idrossiclorochina, Available online: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000898_046074_RCP.pdf&sys=m0b1l3.
57. COVID-SAFER: Deprescribing Guidance for Hydroxychloroquine Drug Interactions in Older Adults10.1111/jgs.16623 ↗
58. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro10.1038/s41422-020-0282-0 ↗
59. Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials
60. Pharmacokinetics of Lopinavir and Ritonavir in Patients Hospitalized with Coronavirus Disease 2019 (COVID-19)10.7326/M20-1550 ↗
61. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro10.1016/j.antiviral.2020.104786 ↗
62. High dose lopinavir/ritonavir does not lead to sufficient plasma levels to inhibit SARS-CoV-2 in hospitalized COVID-19 patients10.3389/fphar.2021.704767 ↗
63. Opioid pharmacokinetic drug-drug interactions
64. Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug-Drug Interactions10.1097/FTD.0000000000000761 ↗
65. Potential drug–drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments10.1111/fcp.12586 ↗
66. Interleukin-6 and cytochrome-P450, reason for concern?10.1007/s00296-012-2423-3 ↗
67. COVID-19 and diabetes mellitus: From pathophysiology to clinical management10.1038/s41574-020-00435-4 ↗
68. Efficacy of favipiravir in COVID-19 treatment: A multi-center randomized study10.1007/s00705-021-04956-9 ↗
69. Combination of (interferon beta-1b, lopinavir/ ritonavir and ribavirin) versus favipiravir in hospitalized patients with non-critical COVID-19: A cohort study10.1371/journal.pone.0252984 ↗
70. One year update on the COVID-19 pandemic: Where are we now?10.1016/j.actatropica.2020.105778 ↗
71. The Role of Glucocorticoids in the Management of COVID-1910.1055/a-1300-2550 ↗
72. Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells10.1177/039463201002300209 ↗
73. Effects of TGF-b and Glucocorticoids on Map Kinase Phosphorylation, IL-6/IL-11 Secretion and Cell Proliferation in Primary Cultures of Human Lung Fibroblasts10.1002/jcp.20884 ↗
74. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-1910.1001/jama.2020.17023 ↗
75. Effect of dexamethasone in patients with ARDS and COVID-19—Prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial10.1186/s13063-020-04976-x ↗
76. Reduced risk of COVID-19 hospitalization in asthmatic and COPD patients: A benefit of inhaled corticosteroids?10.1080/17476348.2021.1850275 ↗
77. The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells10.1128/JVI.01648-20 ↗
78. COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids10.1164/rccm.202003-0821OC ↗
79. Ramakrishnan, S., Nicolau, D.V., Langford, B., Mahdi, M., Jeffers, H., Mwasuku, C., Krassowska, K., Fox, R., Binnian, I., and Glover, V. (2021). Inhaled budesonide in the treatment of early COVID-19 (STOIC): A phase 2, open-label, randomised controlled trial. Lancet Respir. Med., 763–772.10.1016/S2213-2600(21)00160-0 ↗
80. Laurence Brunton, R.H.D., and Goodman & Gillman’s (2021, August 12). The Pharmacological Basis of Therapy; 13th ed.; 2018. Available online: https://accessmedicine.mhmedical.com/book.aspx?bookID=2189#165936881.
81. Drug interactions of psychiatric and COVID-19 medications
82. Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: Integrated evidence from 4 databases and a systematic review10.1007/s00213-020-05716-4 ↗
83. Drugs Behave as Substrates, Inhibitors and Inducers of Human Cytochrome P450 3A410.2174/138920008784220664 ↗
84. Drugs as P-glycoprotein substrates, inhibitors, and inducers10.1081/DMR-120001389 ↗
85. Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation; a consensus document of the Italian federation of thrombosis centers (FCSA)10.1160/TH11-05-0358 ↗
86. Hakkola, J., Hukkanen, J., Turpeinen, M., and Pelkonen, O. (2020). Inhibition and Induction of CYP Enzymes in Humans: An Update, Springer.10.1007/s00204-020-02936-7 ↗
87. European Medicines Agency (2020). Advagraf—Summary of Product Characteristics, European Medicines Agency.
88. European Medicines Agency (2021). Rapamune—Summary of Product Characteristics, European Medicines Agency.
89. European Medicines Agency (2020). Afinitor—Summary of Product Characteristics, European Medicines Agency.
90. AIFA (2021, August 12). Riassunto delle Caratterisiche del Prodotto—Ciqorin; AIFA, Available online: https://farmaci.agenziafarmaco.gov.it/aifa/servlet/PdfDownloadServlet?pdfFileName=footer_000813_042787_RCP.pdf&sys=m0b1l3.
91. Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up10.1016/j.eclinm.2020.100459 ↗
92. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized with COVID-19 Pneumonia10.1001/jamainternmed.2020.6615 ↗
93. Case Report: Disseminated Strongyloidiasis in a Patient with COVID-1910.4269/ajtmh.20-0699 ↗
94. Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia10.1007/s15010-020-01522-4 ↗
95. (2021, August 12). European Medicines Agency RoActemra-Summary of Product Characteristics. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/roactemra.
96. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease10.1016/S0140-6736(20)30304-4 ↗
97. Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis10.1126/scitranslmed.aau5266 ↗
98. Fluvoxamine inhibits some inflammatory genes expression in LPS/stimulated human endothelial cells, U937 macrophages, and carrageenan-induced paw edema in rat
99. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome10.1038/ni.2550 ↗
100. An update to monoclonal antibody as therapeutic option against COVID-1910.1016/j.bsheal.2021.02.001 ↗