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Pharmaco-Immunomodulatory Therapy in COVID-19.
Drugs. 2020 Sep; 80(13):1267-1292.D

Abstract

The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.

Authors+Show Affiliations

Edson College, Arizona State University, Phoenix, AZ, USA. john.rizk@lau.edu.Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine, School of Medicine, Irvine, CA, USA. Department of Epidemiology, University of California, Los Angeles, UCLA Fielding School of Public Health, Los Angeles, CA, USA. Tibor Rubin VA Long Beach Healthcare System, Long Beach, CA, USA.Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.John Ochsner Heart and Vascular Institute, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA, USA.Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon.Division of Infectious Diseases, Department of Medicine, University of California, Irvine, School of Medicine, Irvine, CA, USA. Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine, Irvine, CA, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32696108

Citation

Rizk, John G., et al. "Pharmaco-Immunomodulatory Therapy in COVID-19." Drugs, vol. 80, no. 13, 2020, pp. 1267-1292.
Rizk JG, Kalantar-Zadeh K, Mehra MR, et al. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020;80(13):1267-1292.
Rizk, J. G., Kalantar-Zadeh, K., Mehra, M. R., Lavie, C. J., Rizk, Y., & Forthal, D. N. (2020). Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs, 80(13), 1267-1292. https://doi.org/10.1007/s40265-020-01367-z
Rizk JG, et al. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020;80(13):1267-1292. PubMed PMID: 32696108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmaco-Immunomodulatory Therapy in COVID-19. AU - Rizk,John G, AU - Kalantar-Zadeh,Kamyar, AU - Mehra,Mandeep R, AU - Lavie,Carl J, AU - Rizk,Youssef, AU - Forthal,Donald N, PY - 2020/7/23/pubmed PY - 2020/9/17/medline PY - 2020/7/23/entrez SP - 1267 EP - 1292 JF - Drugs JO - Drugs VL - 80 IS - 13 N2 - The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms. SN - 1179-1950 UR - https://www.unboundmedicine.com/medline/citation/32696108/Pharmaco_Immunomodulatory_Therapy_in_COVID_19_ L2 - https://dx.doi.org/10.1007/s40265-020-01367-z DB - PRIME DP - Unbound Medicine ER -