The cytokine storm and COVID-19

Biying Hu, Shaoying Huang, Lianghong Yin, Biying Hu, Shaoying Huang, Lianghong Yin

Abstract

Coronavirus disease 2019 (COVID-19), which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. More than 4 million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of 11 May 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. In addition, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19.

Keywords: COVID-19; SARS-CoV-2; cytokine storm; literature review.

Conflict of interest statement

The authors declare that there are no conflict of interests.

© 2020 Wiley Periodicals LLC.

References

    1. Bogoch II, Watts A, Thomas‐Bachli A, Huber C, Kraemer MUG, Khan K. Potential for global spread of a novel coronavirus from China. J Travel Med. 2020;27(2):taaa011.
    1. 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.
    1. Huang KJ, Su IJ, Theron M, et al. An interferon‐gamma‐related cytokine storm in SARS patients. J Med Virol. 2005;75(2):185‐194.
    1. Zhou J, Chu H, Li C, et al. Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis. J Infect Dis. 2014;209(9):1331‐1342.
    1. Mehta P, McAuley DF, Brown M, et al. COVID‐19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034.
    1. Corman VM, Muth D, Niemeyer D, Drosten C, et al. Chapter eight—hosts and sources of endemic human coronaviruses. Adv Virus Res. 2018;100:163‐188.
    1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses . The species severe acute respiratory syndrome‐related coronavirus: classifying 2019‐nCoV and naming it SARS‐CoV‐2. Nat Microbiol. 2020;5(4):536‐544.
    1. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565‐574.
    1. Zhou P, Yang X‐L, Wang X‐G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270‐273.
    1. World Health Organization . Coronavirus disease (COVID‐19) situation report , 112. 2020.
    1. Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490‐502.
    1. World Health Organization (WHO) . Report of the WHO‐China joint mission on coronavirus disease 2019 (COVID‐19) . 2020. . Accessed June 5, 2020.
    1. Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID‐19, SARS and MERS: are they closely related? Clin Microbiol Infect. 2020;26:729‐734.
    1. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses 2019. Nat Rev Microbiol. 2019;17:181‐192.
    1. Helmy YA, Fawzy M, Elaswad A, Sobieh A, Kenney SP, Shehata AA. The COVID‐19 pandemic: a comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control. J Clin Med. 2020;9(4):1225.
    1. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses—drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327‐347.
    1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529‐539.
    1. Guan W‐J, Ni Z‐Y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708‐1720.
    1. Feng Y, Ling Y, Bai T, et al. COVID‐19 with different severity: a multi‐center study of clinical features. Am J Respir Crit Care Med. 2020;201:1380‐1388.
    1. Teijaro JR, Walsh KB, Rice S, Rosen H, Oldstone MB. Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. Proc Natl Acad Sci USA. 2014;111(10):3799‐3804.
    1. Merad M, Martin JC. Pathological inflammation in patients with COVID‐19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20:355‐362.
    1. Jia Y, Shen G, Zhang Y, et al. Analysis of the mutation dynamics of SARS‐CoV‐2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity. bioRxiv. 10.1101/2020.04.09.034942
    1. Forster P, Forster L, Renfrew C, Forster M. Phylogenetic network analysis of SARS‐CoV‐2 genomes. Proc Natl Acad Sci USA. 2020;117(17):9241‐9243.
    1. Yao H, Lu X, Chen Q, et al. Patient‐derived mutations impact pathogenicity of SARS‐CoV‐2. medRxiv. 10.1101/2020.04.14.20060160
    1. 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):420‐422.
    1. Yao XH, He ZC, Li TY, et al. Pathological evidence for residual SARS‐CoV‐2 in pulmonary tissues of a ready‐for‐discharge patient. Cell Res. 2020;30:541‐543.
    1. Li H, Liu L, Zhang D, et al. SARS‐CoV‐2 and viral sepsis: observations and hypotheses. Lancet. 2020;395(10235):1517‐1520.
    1. Zhang H, Zhou P, Wei Y, et al. Histopathologic changes and SARS‐CoV‐2 immunostaining in the lung of a patient with COVID‐19. Ann Intern Med. 2020;172(9):629‐632.
    1. Azkur AK, Akdis M, Azkur D, et al. Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19. Allergy. 2020;75(7):1564‐1581.
    1. Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003;200(3):282‐289.
    1. Ng DL, Al Hosani F, Keating MK, et al. Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014. Am J Pathol. 2016;186(3):652‐658.
    1. Parsons PE, Eisner MD, Thompson BT, et al. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005;33(1):1‐6.
    1. Hoffmann M, Kleine‐Weber H, Schroeder S, et al. SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271‐280.
    1. Hussman JP. Cellular and molecular pathways of COVID‐19 and potential points of therapeutic intervention. OSF Preprints. 19 May 2020;Web.
    1. Haiming W, Xiaoling X, Yonggang Z, et al. Aberrant pathogenic GM‐CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. BioRXiv. 10.1101/2020.02.12.945576
    1. Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID‐19. JCI Insight. 2020;5(11):e138999.
    1. Hirano T, Murakami M. COVID‐19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity. 2020;52(5):731‐733.
    1. Eguchi S, Kawai T, Scalia R, Rizzo V. Understanding angiotensin II type 1 receptor signaling in vascular pathophysiology. Hypertension. 2018;71(5):804‐810.
    1. Murakami M, Kamimura D, Hirano T. Pleiotropy and specificity: insights from the interleukin 6 family of cytokines. Immunity. 2019;50(4):812‐831.
    1. Moore JB, June CH. Cytokine release syndrome in severe COVID‐19. Science. 2020;368(6490):473‐474.
    1. Wong CK, Lam CW, Wu AK, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136(1):95‐103.
    1. Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS‐CoV infection in humans is associated with a pro‐inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018;104:8‐13.
    1. 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):2620‐2629.
    1. 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;55:102763.
    1. Ong EZ, Chan YFZ, Leong WY, et al. A dynamic immune response shapes COVID‐19 progression. Cell Host Microbe. 2020;27:879‐882.
    1. Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID‐19 infection and rheumatoid arthritis: faraway, so close! Autoimmun Rev. 2020;19:102523.
    1. Chen R‐C, Tang X‐P, Tan S‐Y, et al. Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience. Chest. 2006;129(6):1441‐1452.
    1. Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019‐nCoV pneumonia. Lancet. 2020;395(10225):683‐684.
    1. NIH COVID‐19 Treatment Guidelines. 2020. . Accessed June 5, 2020.
    1. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019‐nCoV lung injury. Lancet. 2020;395(10223):473‐475.
    1. 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. The Journal of infection. 2020;81:E13‐E20.
    1. Wu S‐F, Chang C‐B, Hsu J‐M, et al. Hydroxychloroquine inhibits CD154 expression in CD4 T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1):183.
    1. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3(11):722‐727.
    1. Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Clin Infect Dis. 2020;71(15):732‐739.
    1. Gautret P, Lagier J‐C, Parola P, 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(1):105949.
    1. Shamshirian A, Hessami A, Heydari K, et al. The Role of Hydroxychloroquine in the Age of COVID‐19: a Periodic Systematic Review and Meta‐Analysis. medRxiv. 10.1101/2020.04.14.20065276
    1. Al‐Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70(6):1608‐1621.
    1. Borba MGS, de Almeida Val F, Sampaio VS, et al. Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS‐CoV‐2) infection: preliminary safety results of a randomized, double‐blinded, phase IIb clinical trial (CloroCovid‐19 study). medRxiv. 2020. 10.1101/2020.04.07.20056424
    1. Lane JCE, Weaver J, Kostka K, et al. Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide‐spread use for COVID‐19: a multinational, network cohort and self‐controlled case series study. medRxiv. 10.1101/2020.94.08.20054551
    1. Zhang C, Wu Z, Li J‐W, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID‐19 and interleukin‐6 receptor (IL‐6R) antagonist tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020;55:105954.
    1. Chinese Clinical Trail Registry . A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia . 2020. . Accessed March 24, 2020.
    1. Xu X, Han M, Li T, et al. Effective treatment of severe COVID‐19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020;117(20):10970‐10975.
    1. Wadud N, Ahmed N, Mannu Shergil M, et al. Improved survival outcome in SARs‐CoV‐2 (COVID‐19) acute respiratory distress syndrome patients with tocilizumab administration. medRxiv. 10.1101/2020.05.13.20100081
    1. Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Clin Drug Invest. 2020;40(6):511‐518.
    1. Arnaldez FI, O'Day SJ, Drake CG, et al. The Society for Immunotherapy of Cancer perspective on regulation of interleukin‐6 signaling in COVID‐19‐related systemic inflammatory response. J Immunother Cancer. 2020;8(1):e000930.
    1. EULAR guidance for patients during COVID‐19 outbreak. 2020. . Accessed April 23, 2020.
    1. BSR guidance for patients during COVID‐19 outbreak. Rheumatolupdate‐members. 2020. . Accessed April 20, 2020.
    1. ACR guidance for patients during COVID‐19 outbreak. 2020. . Accessed April 20, 2020.
    1. Australian Rheumatology Association guidance for patients during COVID‐19 outbreak. 2020. . Accessed April 20, 2020.
    1. Uccelli A, de Rosbo NK. The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. Ann NY Acad Sci. 2015;1351:114‐126.
    1. Chen J, Hu C, Chen L, et al. Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID‐19 treatment. [published online ahead of print, 2020 Feb 28] Engineering (Beijing). 10.1016/j.eng.2020.02.006
    1. Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2− mesenchymal stem cells improves the outcome of patients with COVID‐19 pneumonia. Aging Dis. 2020;11(2):216‐228.
    1. Cavalli G, De Luca G, Campochiaro C, et al. Interleukin‐1 blockade with high‐dose anakinra in patients with COVID‐19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2:325.
    1. Arabi YM, Shalhoub S, Mandourah Y, et al. Ribavirin and interferon therapy for critically Ill patients with Middle East respiratory syndrome: a multicenter observational study. Clin Infect Dis. 2020;70(9):1837‐1844.
    1. 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(2):318‐356.
    1. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019‐nCoV acute respiratory disease. Lancet. 2020;395(10223):e30‐e31.
    1. Liu Q, Zhou Y‐H, Yang Z‐Q. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016;13(1):3‐10.
    1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507‐513.
    1. Alijotas‐Reig J, Esteve‐Valverde E, Belizna C, et al. Immunomodulatory therapy for the management of severe COVID‐19. Beyond the anti‐viral therapy: a comprehensive review. Autoimmun Rev. 2020;19:102569.
    1. Mair‐Jenkins J, Saavedra‐Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta‐analysis. J Infect Dis. 2015;211(1):80‐90.
    1. Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52(4):447‐456.
    1. Valk SJ, Piechotta V, Chai KL, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a rapid review. Cochrane Database Syst Rev. 2020;5(5):D013600.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다