Cytokines mediated hyperinflammation in SARS-CoV2: An Overview
Abstract
Hyperinflammation induced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is a major cause of disease severity and mortality in infected patients. The immunopathogenesis of SARS-CoV2 infection is similar to the previous Middle East Respiratory Syndrome-related coronavirus (MERS-CoV) and SARS-CoV coronavirus with severe inflammatory responses. Therefore, severity of this viral infection is not only associated with the virus but also due to host immune responses. Hyperinflammatory responses due to cytokine storm are a centerpiece of SARS-CoV2 pathogenesis with overwhelming consequences for the host. Virus infected monocyte derived macrophages produce cytokines and this contributes to damage of lymphoid tissue and limits the lymphocyte responses. Blocking the deadly cytokine storm and T lymphocyte stimulation is a vital defense for treating SARS-CoV2. Here, we will describe the role of hyperinflamation and the involvement of cytokines in severe SARS-CoV2 infection.
References
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020; 53: 25-32.
Wei X, Li X, Cui J. Evolutionary perspectives on novel coronaviruses identified in pneumonia cases in China. National Science Review. 2020; 7: 239-42.
CRS Report, 2020. Congressional Research Service.
Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology. 2020; 28: 1-2.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine. 2020; 382: 1708-20.
Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clinical & Experimental Immunology. 2004; 136: 95-103.
Fung TS, Liu DX. Human coronavirus: host-pathogen interaction. Annual review of microbiology. 2019; 73: 529- 57.
Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virology journal. 2019; 16: 1-22.
Kirchdoerfer RN, Cottrell CA, Wang N, Pallesen J, Yassine HM, Turner HL, et al. Pre-fusion structure of a human coronavirus spike protein. Nature. 2016; 531: 118-21.
Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging microbes & infections. 2020; 9: 221-36.
Malik YS, Sircar S, Bhat S, Sharun K, Dhama K, Dadar M, et al. Emerging novel Coronavirus (SARS-CoV2)-Current scenario, evolutionary perspective based on genome analysis and recent developments. Vet Q. 2020: 40: 68–76.
Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell host & microbe. 2020; 27: 325-8.
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020.
Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to SARS- CoV2 infection. Front Med. 2020; 14: 185–92.
Shang J, Wan Y, Liu C, Yount B, Gully K, Yang Y, et al. Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. PLoS pathogens. 2020; 16: e1008392.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England). 2020; 395: 1033-4.
Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, et al. The protein tyrosine kinase JAK1 complements defects in interferon-α/β and-γ signal transduction. Nature. 1993; 366: 129-35.
Qi QR, Yang ZM. Regulation and function of signal transducer and activator of transcription 3. World J Biol Chem. 2014; 5: 231–9.
Olofsson TB. Growth regulation of hematopoietic cells: an overview. Acta Oncologica. 1991; 30: 889-902.
Herrmann SM, Ricard S, Nicaud V, Mallet C, Arveiler D, Evans A, et al. Polymorphisms of the tumour necrosis factor-α gene, coronary heart disease and obesity. European journal of clinical investigation. 1998 ; 28: 59-66.
Schoenborn JR, Wilson CB. Regulation of interferon-γ during innate and adaptive immune responses. Advances in immunology. 2007; 96: 41-101.
Beutler BA. TLRs and innate immunity. Blood, The Journal of the American Society of Hematology. 2009; 113: 1399-407.
Görlich D, Hartmann E, Prehn S, Rapoport TA. A protein of the endoplasmic reticulum involved early in polypeptide translocation. Nature. 1992; 357: 47-52.
Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, et al. A fourth IκB protein within the NF-κB signaling module. Cell. 2007; 128: 369-81.
Li S, Strelow A, Fontana EJ, Wesche H. IRAK-4: a novel member of the IRAK family with the properties of an IRAK- kinase. Proceedings of the National Academy of Sciences. 2002; 99: 5567-72.
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426: 450-4.
Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC.
CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990; 249: 1431-3.
Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of
viral RNA. Immunity. 2009; 30: 556-65.
Harris TH, Banigan EJ, Christian DA, Konradt C, Wojno ED, Norose K, et al. Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature. 2012; 486: 545-8.
Zhang Q, Zhao K, Shen Q,HanY, Gu Y,Li X, et al. Tet 2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature. 2015; 525: 389-93.
Franchimont D, Martens H, Hagelstein MT, Louis E, Dewe W, Chrousos GP, et al. Tumor necrosis factor α decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor. The Journal of Clinical Endocrinology & Metabolism. 1999; 84: 2834-9.
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature Reviews Immunology. 2020; 6: 1-8.
Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, et al. Clinical characteristics of 82 death cases with COVID-19. MedRxiv. 2020.
Feng Z, Diao B, Wang R, Wang G, Wang C, Tan Y, et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. MedRxiv. 2020.
Hur S. Double-stranded RNA sensors and modulators in innate immunity. Annual review of immunology. 2019; 37: 349-75.
Chu H, Chan JF, Wang Y, Yuen TT, Chai Y, Hou Y, et al. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clinical Infectious Diseases. 2020; 71: 1400–9.
Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181: 1036-45.
Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. Journal of medical virology. 2020; 92: 424-32.
Clay C, Donart N, Fomukong N, Knight JB, Lei W, Price L, et al. Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge. Journal of virology. 2012; 86: 4234-44.
Huang AT, Garcia-Carreras B, Hitchings MD, Yang B, Katzelnick LC, Rattigan SM, et al. A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv. 2020.
Wang K, Chen W, Zhou YS, Lian JQ, Zhang Z, Du P, et al. SARS- CoV-2 invades host cells via a novel route: CD147-spike protein. BioRxiv. 2020.
ZhengM,GaoY,WangG,SongG,LiuS,SunD,etal. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cellular & molecular immunology. 2020; 17: 533-5.
Schulert GS, Grom AA. Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies. Annual review of medicine. 2015; 66: 145-59.
Mouy R, Stephan JL, Pillet P, Haddad E, Hubert P, Prieur AM. Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: report of five cases. The Journal of pediatrics. 1996; 129: 750-4.
Quesnel B, Catteau B, Aznar V, Bauters F, Fenaux P. Successful treatment of juvenile rheumatoid arthritis associated haemophagocytic syndrome by cyclosporin A with transient exacerbation by conventional-dose G-CSF. British journal of haematology. 1997; 97: 508-10.
Coca A, Bundy KW, Marston B, Huggins J, Looney RJ. Macrophage activation syndrome: serological markers and treatment with anti-thymocyte globulin. Clinical mmunology. 2009; 132: 10-8.
Xu L, Chen G. Risk factors for severe corona virus disease 2019 (COVID-19) patients: a systematic review and meta analysis. medRxiv. 2020.
Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity. 2019; 50: 1007-23.
Didangelos A. COVID-19 Hyperinflammation: What about Neutrophils?. MSphere. 2020; 5.
Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H, Mahajan VS, et al. Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19 . Cell. 2020; 183: 1–15.
