Generic placeholder image

Current Pharmaceutical Design

Author(s): Monireh Torabi-Rahvar and Nima Rezaei*

DOI: 10.2174/1381612826666201125102649

DownloadDownload PDF Flyer Cite As
Storm at the Time of Corona: A Glimpse at the Current Understanding and Therapeutic Opportunities of the SARS-CoV-2 Cytokine Storm

Page: [1549 - 1552] Pages: 4

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to severe disease in some cases, leading to acute respiratory distress syndrome, multi-organ failure, and death. This severe phenotype seems to be associated with a cytokine storm and immune dysregulation. Increased pro-inflammatory cytokines and CD14+CD16+ inflammatory monocytes, lymphopenia, and decreased levels of regulatory T cells are some of the immunological features that are seen in patients with SARS-CoV-2. As the outcome of SARS-CoV-2 is influenced by both viral virulence and dysregulated inflammatory response, a combination therapy approach using antiviral drugs plus anti-inflammatory treatments, such as corticosteroids, monoclonal antibodies against the IL-6 and IL-1β pathways, and JAK inhibitors are under clinical trials.

Keywords: Severe acute respiratory syndrome coronavirus 2, cytokine storm, proinflammatory cytokines, monoclonal antibodies, inflammatory, IL-1β.

[1]
Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020; 20(5): 269-70.
[http://dx.doi.org/10.1038/s41577-020-0308-3] [PMID: 32273594]
[2]
Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol 2020; 2(6): e358-67.
[3]
Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55102763
[http://dx.doi.org/10.1016/j.ebiom.2020.102763] [PMID: 32361250]
[4]
Yazdanpanah F, Hamblin MR, Rezaei N. The immune system and COVID-19: Friend or foe? Life Sci 2020; 256117900
[http://dx.doi.org/10.1016/j.lfs.2020.117900] [PMID: 32502542]
[5]
Zhang B, Zhou X, Zhu C, et al. Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19 medRxiv 2020; 7: 157.
[6]
Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130(5): 2620-9.
[http://dx.doi.org/10.1172/JCI137244] [PMID: 32217835]
[7]
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8(4): 420-2.
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[8]
Fathi N, Rezaei N. Lymphopenia in COVID-19: Therapeutic opportunities. Cell Biol Int 2020; 44(9): 1792-7.
[http://dx.doi.org/10.1002/cbin.11403] [PMID: 32458561]
[9]
Zhou Y, Fu B, Zheng X, Wang D, Zhao C. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev 2020.nwaa041
[http://dx.doi.org/10.1093/nsr/nwaa041]
[10]
Liao M, Liu Y, Yuan J, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing. medRxiv 2020.
[11]
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020; 71(15): 762-8.
[12]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[13]
Lotfi M, Rezaei N. SARS-CoV-2: A comprehensive review from pathogenicity of the virus to clinical consequences. J Med Virol 2020; 92(10): 1864-74.
[http://dx.doi.org/10.1002/jmv.26123] [PMID: 32492197]
[14]
Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: current state of the science. Immunity 2020; 52(6): 910-41.
[http://dx.doi.org/10.1016/j.immuni.2020.05.002] [PMID: 32505227]
[15]
Deftereos SG, Siasos G, Giannopoulos G, 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(1): 42-5.
[http://dx.doi.org/10.1016/j.hjc.2020.03.002] [PMID: 32251729]
[16]
Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 2020; 583(7816): 459-68.
[http://dx.doi.org/10.1038/s41586-020-2286-9] [PMID: 32353859]
[17]
Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020; 53(3): 368-70.
[http://dx.doi.org/10.1016/j.jmii.2020.03.005] [PMID: 32205092]
[18]
Kindler E, Thiel V, Weber F. Interaction of SARS and MERS coronaviruses with the antiviral interferon response Advances in virus research 96. Elsevier 2016; pp. 219-43.
[19]
de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14(8): 523-34.
[http://dx.doi.org/10.1038/nrmicro.2016.81] [PMID: 27344959]
[20]
Lotfi M, Hamblin MR, Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020; 508: 254-66.
[http://dx.doi.org/10.1016/j.cca.2020.05.044] [PMID: 32474009]
[21]
Brun-Buisson C, Richard J-CM, Mercat A, Thiébaut AC, Brochard L. Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. Am J Respir Crit Care Med 2011; 183(9): 1200-6.
[http://dx.doi.org/10.1164/rccm.201101-0135OC] [PMID: 21471082]
[22]
Zumla A, Chan JF, Azhar EI, Hui DS, Yuen K-Y. Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov 2016; 15(5): 327-47.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[23]
Li H, Chen C, Hu F, et al. Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis. Leukemia 2020; 34(6): 1503-11.
[http://dx.doi.org/10.1038/s41375-020-0848-3] [PMID: 32372026]
[24]
Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020; 81(1): e13-20.
[http://dx.doi.org/10.1016/j.jinf.2020.03.062] [PMID: 32283144]
[25]
Jin Y-H, Cai L, Cheng Z-S, 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.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[26]
Wu C, Chen X, Cai Y, 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; 180(7): 934-43.
[http://dx.doi.org/10.1001/jamainternmed.2020.0994] [PMID: 32167524]
[27]
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
[http://dx.doi.org/10.1016/S0140-6736(20)30317-2] [PMID: 32043983]
[28]
Zhou W, Liu Y, Tian D, et al. Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia. Signal Transduct Target Ther 2020; 5(1): 18.
[http://dx.doi.org/10.1038/s41392-020-0127-9] [PMID: 32296012]
[29]
Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther 2020; 5(1): 57.
[http://dx.doi.org/10.1038/s41392-020-0158-2] [PMID: 32341331]
[30]
Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect 2020; 9(1): 1123-30.
[http://dx.doi.org/10.1080/22221751.2020.1770129] [PMID: 32475230]
[31]
Zhang X, Song K, Tong F, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv 2020; 4(7): 1307-10.
[http://dx.doi.org/10.1182/bloodadvances.2020001907] [PMID: 32243501]
[32]
Michot J-M, Albiges L, Chaput N, et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol 2020; 31(7): 961-4.
[http://dx.doi.org/10.1016/j.annonc.2020.03.300] [PMID: 32247642]
[33]
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol 2020; 92(7): 814-8.
[http://dx.doi.org/10.1002/jmv.25801] [PMID: 32253759]
[34]
Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020; 18(1): 164.
[http://dx.doi.org/10.1186/s12967-020-02339-3] [PMID: 32290839]
[35]
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(6)105982
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105982] [PMID: 32305588]
[36]
Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of the macrophage activation syndrome: Re-analysis of a prior Phase III trial. Crit Care Med 2016; 44(2): 275-81.
[http://dx.doi.org/10.1097/CCM.0000000000001402] [PMID: 26584195]
[37]
Miettunen PM, Narendran A, Jayanthan A, Behrens EM, Cron RQ. Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology (Oxford) 2011; 50(2): 417-9.
[http://dx.doi.org/10.1093/rheumatology/keq218] [PMID: 20693540]
[38]
Risitano AM, Mastellos DC, Huber-Lang M, et al. Complement as a target in COVID-19? Nat Rev Immunol 2020; 23: 1-2.