Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines

Antonella Fara, Zan Mitrev, Rodney Alexander Rosalia, Bakri M Assas, Antonella Fara, Zan Mitrev, Rodney Alexander Rosalia, Bakri M Assas

Abstract

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term 'cytokine storm syndrome' is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.

Keywords: COVID-19; IFN-γ; IL-6; SARS; TNF-α; coronavirus.

Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
CS symptoms in COVID-19 and disease progression. Clinical symptoms of COVID-19 can be related to those associated with cytokine storm. Delayed detection of symptoms may lead to disease progression, with multi-organ involvement. It is difficult to manage and requires the admission of patients to ICU; intensive care is observed in about 5% of the infected population. Of the critically ill COVID-19 patients, the mortality rate is high, 40–50% [2,7].
Figure 2.
Figure 2.
ACE2 expression in human tissues. SARS-Cov-2 uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. ACE2 RNA and protein expression were observed in the endocrine tissues, gastrointestinal tract, the kidney and urinary bladder, the liver and gallbladder in men and women [7].
Figure 3.
Figure 3.
Prominent cytokine sources and their effect in COVID-19 pathogenesis. Immune cell sources of cytokines associated with cytokine storms; IFN-γ, TNF-α, IL-1 and IL-6 are depicted with their effects in the context of COVID-19 [7].
Figure 4.
Figure 4.
Viral entry, replication and innate immune activation. Multiple distinct toll-like-receptors (TLRs) pathways are involved in SARS-CoV-2 pathogenesis. SARS-Cov-2 cellular entry and subsequent replication (a) may trigger the immune system by engaging multiple TLRs (b). The spike protein triggers TLR4, ssRNA activates TLR7 and dsRNA may lead to TLR3 activation. Following TLR activation, IRFs and NF-κB-dependent signalling pathways are activated leading to type I/II Interferons and pro-inflammatory cytokines [7].
Figure 5.
Figure 5.
ARDS is acute condition occurring within 1 week of clinical insult, or the onset of respiratory symptoms, characterized by bilateral pulmonary immune infiltrates and severe hypoxaemia in the absence of cardiac failure or pulmonary edema. The condition is characterized by severity levels based on the PaO2/FiO2 ratio; mild (PaO2/FiO2 200–300), moderate (PaO2/FiO2 100–200), and severe (PaO2/FiO2 ≤ 100) [7].

References

    1. Cucinotta D, Vanelli M. 2020. WHO declares COVID-19 a pandemic. Acta Biomed. 91, 157–160. (10.23750/abm.v91i1.9397)
    1. Ronco C, Reis T, De Rosa S.. 2020. Coronavirus epidemic and extracorporeal therapies in intensive care: si vis pacem para bellum. Blood Purification 49, 255–258. (10.1159/000507039)
    1. Huang C, et al. . 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395, 497–506. (10.1016/S0140-6736(20)30183-5)
    1. Zhou F, et al. . 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062. (10.1016/S0140-6736(20)30566-3)
    1. Hu H, Ma F, Wei X, Fang Y. 2020. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Eur. Heart J. 16, ehaa190 (10.1093/eurheartj/ehaa190)
    1. Ruan Q, Yang K, Wang W, Jiang L, Song J. 2020. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 46, 846–848. (10.1007/s00134-020-05991-x)
    1. Biorender. 2020. Home. See
    1. Wu C, et al. . 2020. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Med. 180, 934–943. (10.1001/jamainternmed.2020.0994)
    1. NIH. 2020. Management of COVID-19 See .
    1. Peng PWH, Ho P-L, Hota SS. 2020. Outbreak of a new coronavirus: what anaesthetists should know. Br. J. Anaesth. 124, 497–501. (10.1016/j.bja.2020.02.008)
    1. Cennimo DJ. 2020. Coronavirus disease 2019 (COVID-19) guidelines: CDC interim guidance on coronavirus disease 2019 (COVID-19). Accessed 23 March 2020 See .
    1. National Health Commission, National Administration of Traditional Chinese Medicine. 2020. Diagnosis and treatment protocol for novel coronavirus pneumonia. Chin. Med. J. 133, 1087–1095.
    1. Poston JT, Patel BK, Davis AM. 2020. Management of critically ill adults with COVID-19. JAMA. 323, 1839–1841. (10.1001/jama.2020.4914)
    1. Li M.-Y., Li L, Zhang Y, Wang X.-S. 2020. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infectious Dis. Poverty 9, 45 (10.1186/s40249-020-00662-x)
    1. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H.. 2004. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus: a first step in understanding SARS pathogenesis. J. Pathol. 203, 631–637. (10.1002/path.1570)
    1. Uhlen M, et al. . 2015. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (10.1126/science.1260419)
    1. Goulter AB, Goddard MJ, Allen JC, Clark KL. 2004. ACE2 gene expression is up-regulated in the human failing heart. BMC Med. 2, 19 (10.1186/1741-7015-2-19)
    1. Danilczyk U, Penninger JM. 2006. Angiotensin-converting enzyme II in the heart and the kidney. Circul. Res. 98, 463–471. (10.1161/01.RES.0000205761.22353.5f)
    1. Clark IA, Virelizier JL, Carswell EA, Wood PR. 1981. Possible importance of macrophage-derived mediators in acute malaria. Infect Immun. 32, 1058–1066. (10.1128/IAI.32.3.1058-1066.1981)
    1. Clark IA. 1982. Suggested importance of monokines in pathophysiology of endotoxin shock and malaria. Klin Wochenschr. 60, 756–758. (10.1007/BF01716573)
    1. Makhija R, Kingsnorth AN. 2002. Cytokine storm in acute pancreatitis. J. Hepatobiliary Pancreat. Surg. 9, 401–410. (10.1007/s005340200049)
    1. Jahrling PB, Hensley LE, Martinez MJ, Leduc JW, Rubins KH, Relman DA, Huggins JW. 2004. Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. Proc. Natl Acad. Sci. USA 101, 15 196–15 200. (10.1073/pnas.0405954101)
    1. Yuen KY, Wong SS. 2005. Human infection by avian influenza A H5N1. Hong Kong Med. J. 11, 189–199.
    1. Ferrara JL, Abhyankar S, Gilliland DG. 1993. Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. Transplant Proc. 25, 1216–1217. (10.1097/00007890-199312000-00045)
    1. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. 2012. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 76, 16–32. (10.1128/MMBR.05015-11)
    1. Zhao L, Cao YJ. 2019. Engineered T cell therapy for cancer in the clinic. Front. Immunol. 10, 2250–2250 (10.3389/fimmu.2019.02250)
    1. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N. 2006. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. New Engl. J. Med. 355, 1018–1028. (10.1056/NEJMoa063842)
    1. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. 2010. The safety and side effects of monoclonal antibodies. Nat. Rev. Drug Discov. 9, 325–338. (10.1038/nrd3003)
    1. Honjo O, Kubo T, Sugaya F, Nishizaka T, Kato K, Hirohashi Y, Takahashi H, Torigoe T. 2019. Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report. J. ImmunoTherapy Cancer 7, 97 (10.1186/s40425-019-0582-4)
    1. Ceschi A, Noseda R, Palin K, Verhamme K. 2020. Immune checkpoint inhibitor-related cytokine release syndrome: analysis of WHO global pharmacovigilance database. Front. Pharmacol. 11, 557 (10.3389/fphar.2020.00557)
    1. Bakacs T, Mehrishi JN, Moss RW. 2012. Ipilimumab (Yervoy) and the TGN1412 catastrophe. Immunobiology 217, 583–589. (10.1016/j.imbio.2011.07.005)
    1. Zhang Y, et al. . 2004. Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infect. Immun. 72, 4410–4415. (10.1128/IAI.72.8.4410-4415.2004)
    1. Min CK, et al. . 2016. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci. Rep. 6, 25359 (10.1038/srep25359)
    1. Rosalia RA, et al. 2013. Administration of anti-CD25 mAb leads to impaired α-galactosylceramide-mediated induction of IFN-γ production in a murine model. Immunobiology 218, 851–859. (10.1016/j.imbio.2012.10.012)
    1. Parkin J, Cohen B. 2001. An overview of the immune system. Lancet 357, 1777–1789. (10.1016/S0140-6736(00)04904-7)
    1. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR, Klucher K, Staeheli P. 2008. Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog. 4, e1000151 (10.1371/journal.ppat.1000151)
    1. Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. 2020. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol. Immunol. 17, 533–535. (10.1038/s41423-020-0402-2)
    1. Pedersen SF, Ho YC. 2020. SARS-CoV-2: a storm is raging. J. Clin. Invest. 130, 2202–2205. (10.1172/JCI137647)
    1. Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. 2018. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine 104, 8–13. (10.1016/j.cyto.2018.01.025)
    1. Wong CK, et al. 2004. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 136, 95–103. (10.1111/j.1365-2249.2004.02415.x)
    1. Prompetchara E, Ketloy C, Palaga T. 2020. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac. J. Allergy Immunol. 38, 1–9. (10.12932/AP-200220-0772)
    1. Chen G, et al. 2020. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130, 2620–2629. (10.1172/JCI137244)
    1. Shi Y, et al. 2020. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 27, 1451–1454. (10.1038/s41418-020-0530-3)
    1. Chan MC, et al. 2005. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir. Res. 6, 135 (10.1186/1465-9921-6-135)
    1. Lee SM, et al. 2008. Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection. J. Infect. Dis. 198, 525–535. (10.1086/590499)
    1. Rosalia RA, Arenas-Ramirez N, Bouchaud G, Raeber ME, Boyman O. 2014. Use of enhanced interleukin-2 formulations for improved immunotherapy against cancer. Curr. Opin. Chem. Biol. 23, 39–46. (10.1016/j.cbpa.2014.09.006)
    1. Herrmann F, Oster W, Meuer SC, Lindemann A, Mertelsmann RH. 1988. Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor. J. Clin. Invest. 81, 1415–1418. (10.1172/JCI113471)
    1. Lichtman AH, Chin J, Schmidt JA, Abbas AK. 1988. Role of interleukin 1 in the activation of T lymphocytes. Proc. Natl Acad. Sci. USA 85, 9699–9703. (10.1073/pnas.85.24.9699)
    1. Taylor-Robinson AW, Phillips RS. 1994. Expression of the IL-1 receptor discriminates Th2 from Th1 cloned CD4+ T cells specific for Plasmodium chabaudi. Immunology 81, 216–221.
    1. Nakae S, et al. 2003. IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response. Int. Immunol. 15, 483–490. (10.1093/intimm/dxg054)
    1. Helmby H, Grencis RK. 2004. Interleukin 1 plays a major role in the development of Th2-mediated immunity. Eur. J. Immunol. 34, 3674–3681. (10.1002/eji.200425452)
    1. Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC. 2006. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203, 1685–1691. (10.1084/jem.20060285)
    1. van de Veerdonk FL, Teirlinck AC, Kleinnijenhuis J, Kullberg BJ, van Crevel R, van der Meer JW, Joosten LA, Netea MG.. 2010. Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. J. Leukoc. Biol. 88, 227–232. (10.1189/jlb.0809550)
    1. Schmitz N, Kurrer M, Bachmann MF, Kopf M. 2005. Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J. Virol. 79, 6441–6448. (10.1128/JVI.79.10.6441-6448.2005)
    1. Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT. 2020. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol. Immunol. 17, 541–543. (10.1038/s41423-020-0401-3)
    1. Dienz O, Rincon M. 2009. The effects of IL-6 on CD4 T cell responses. Clin. Immunol. 130, 27–33. (10.1016/j.clim.2008.08.018)
    1. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133. (10.1016/j.cell.2006.07.035)
    1. Yang R, Masters AR, Fortner KA, Champagne DP, Yanguas-Casas N, Silberger DJ, Weaver CT, Haynes L, Rincon M. 2016. IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21-producing B helper CD8+ T cells. J. Exp. Med. 213, 2281–2291. (10.1084/jem.20160417)
    1. Dominitzki S, et al. 2007. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells. J. Immunol. 179, 2041–2045. (10.4049/jimmunol.179.4.2041)
    1. Zhang X, Wu K, Wang D, Yue X, Song D, Zhu Y, Wu J. 2007. Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. Virology 365, 324–335. (10.1016/j.virol.2007.04.009)
    1. Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. 2020. IL-6: relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 53, 13–24. (10.1016/j.cytogfr.2020.05.009)
    1. Lin L, Lu L, Cao W, Li T. 2020. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg. Microbes Infect. 9, 727–732. (10.1080/22221751.2020.1746199)
    1. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, Bergwelt-Baildon MV, Klein M, Weinberger T. 2020. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J. Allergy Clin. Immunol. 146, 128–136. (10.1016/j.jaci.2020.05.008)
    1. Yonggang ZBF, et al. 2020. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci. Rev. 13, nwaa041.
    1. Magro G. 2020. SARS-CoV-2 and COVID-19: is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? What is there besides Tocilizumab? SGP130Fc. Cytokine X. 100029 (10.1016/j.cytox.2020.100029)
    1. Grifoni A, et al. . 2020. Targets of T Cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489–1501. (10.1016/j.cell.2020.05.015)
    1. Salvatori G, Luberto L, Maffei M, Aurisicchio L, Roscilli G, Palombo F, Marra E. 2020. SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines. J. Transl. Med. 18, 222 (10.1186/s12967-020-02392-y)
    1. Barberis M, Helikar T, Verbruggen P. 2018. Simulation of stimulation: cytokine dosage and cell cycle crosstalk driving timing-dependent T cell differentiation. Front. Physiol. 9, 879 (10.3389/fphys.2018.00879)
    1. Cox MA, Harrington LE, Zajac AJ. 2011. Cytokines and the inception of CD8 T cell responses. Trends Immunol. 32, 180–186. (10.1016/j.it.2011.01.004)
    1. Condotta SA, Richer MJ. 2017. The immune battlefield: the impact of inflammatory cytokines on CD8+ T-cell immunity. PLoS Pathog. 13, e1006618 (10.1371/journal.ppat.1006618)
    1. Chen Z, John Wherry E. 2020. T cell responses in patients with COVID-19. Nat. Rev. Immunol. 20, 529 (10.1038/s41577-020-0402-6)
    1. Chang D, et al. 2020. Persistent viral presence determines the clinical course of the disease in COVID-19. J. Allergy Clin. Immunol. Pract. S2213–2198(2220)30614–30610 (10.1016/j.jaip.2020.06.015)
    1. Lucas C, et al. 2020. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584, 463–469. (10.1038/s41586-020-2588-y)
    1. Perlman S. 2020. COVID-19 poses a riddle for the immune system. Nature 584, 345–346. (10.1038/d41586-020-02379-1)
    1. Lescure F-X, et al. . 2020. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect. Dis. 20, 697–706. (10.1016/S1473-3099(20)30200-0)
    1. Raeber ME, Zurbuchen Y, Impellizzieri D, Boyman O. 2018. The role of cytokines in T-cell memory in health and disease. Immunol. Rev. 283, 176–193. (10.1111/imr.12644)
    1. Boyman O, Létourneau S, Krieg C, Sprent J. 2009. Homeostatic proliferation and survival of naïve and memory T cells. Eur. J. Immunol. 39, 2088–2094. (10.1002/eji.200939444)
    1. Boyman O, Purton JF, Surh CD, Sprent J. 2007. Cytokines and T-cell homeostasis. Curr. Opin. Immunol. 19, 320–326. (10.1016/j.coi.2007.04.015)
    1. Tough DF, Borrow P, Sprent J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947–1950. (10.1126/science.272.5270.1947)
    1. Zhang X, Sun S, Hwang I, Tough DF, Sprent J. 1998. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591–599. (10.1016/s1074-7613(00)80564-6)
    1. Kim J, Lee JY, Cho K, Hong S.-W., Kim KS, Sprent J, Im S.-H., Surh CD, Cho J.-H. 2018. Spontaneous proliferation of CD4+ T cells in RAG-deficient hosts promotes antigen-independent but IL-2-dependent strong proliferative response of naïve CD8+ T cells. Front. Immunol. 9, 1907 (10.3389/fimmu.2018.01907)
    1. Arenas-Ramirez N, et al. 2016. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci. Transl. Med. 8, 367ra166 (10.1126/scitranslmed.aag3187)
    1. Freeman BE, Hammarlund E, Raué H-P, Slifka MK. 2012. Regulation of innate CD8+ T-cell activation mediated by cytokines. Proc. Natl Acad. Sci. USA 109, 9971–9976. (10.1073/pnas.1203543109)
    1. Berg RE, Crossley E, Murray S, Forman J. 2003. Memory CD8+ T cells provide innate immune protection against Listeria monocytogenes in the absence of cognate antigen. J. Exp. Med. 198, 1583–1593. (10.1084/jem.20031051)
    1. Suwannasaen D, Romphruk A, Leelayuwat C, Lertmemongkolchai G. 2010. Bystander T cells in human immune responses to dengue antigens. BMC Immunol. 11, 47 (10.1186/1471-2172-11-47)
    1. Zhao C, Zhao W. 2020. NLRP3 inflammasome-a key player in antiviral responses. Front. Immunol. 11, 211 (10.3389/fimmu.2020.00211)
    1. Li G, et al. 2020. Coronavirus infections and immune responses. J. Med. Virol. 92, 424–432. (10.1002/jmv.25685)
    1. Jain A, et al. 2020. T cells instruct myeloid cells to produce inflammasome-independent IL-1β and cause autoimmunity. Nat. Immunol. 21, 65–74. (10.1038/s41590-019-0559-y)
    1. Prilutskiy A, et al. 2020. SARS-CoV-2 infection-associated hemophagocytic lymphohistiocytosis. Amer. J. Clin. Pathol. (10.1093/ajcp/aqaa124)
    1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, HLH Across Speciality Collaboration UK. 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395, 1033–1034. (10.1016/S0140-6736(20)30628-0)
    1. Henter JI, et al. 2007. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood Cancer 48, 124–131. (10.1002/pbc.21039)
    1. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. 2014. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthr. Rheumatol. 66, 2613–2620. (10.1002/art.38690)
    1. Debaugnies F, Mahadeb B, Ferster A, Meuleman N, Rozen L, Demulder A, Corazza F. 2016. Performances of the H-score for diagnosis of hemophagocytic lymphohistiocytosis in adult and pediatric patients. Amer. J. Clin. Pathol. 145, 862–870. (10.1093/ajcp/aqw076)
    1. Gadiparthi C, Bassi M, Yegneswaran B, Ho S, Pitchumoni CS. 2020. Hyperglycemia, hypertriglyceridemia, and acute pancreatitis in COVID-19 infection: clinical implications. Pancreas 49, e62–e63. (10.1097/mpa.0000000000001595)
    1. Kernan KF, Carcillo JA. 2017. Hyperferritinemia and inflammation. Int. Immunol. 29, 401–409. (10.1093/intimm/dxx031)
    1. Zhou P, et al. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273. (10.1038/s41586-020-2012-7)
    1. Hoffmann M, et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280. (10.1016/j.cell.2020.02.052)
    1. McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. 2020. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res. 157, 104859 (10.1016/j.phrs.2020.104859)
    1. Mazaleuskaya L, Veltrop R, Ikpeze N, Martin-Garcia J, Navas-Martin S. 2012. Protective role of Toll-like Receptor 3-induced type I interferon in murine coronavirus infection of macrophages. Viruses 4, 901–923. (10.3390/v4050901)
    1. Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, Baric RS. 2015. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio 6, e00638-15 (10.1128/mBio.00638-15)
    1. Astuti IY. 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab. Syndr. 14, 407–412. (10.1016/j.dsx.2020.04.020)
    1. Angelopoulou A, Alexandris N, Konstantinou E, Mesiakaris K, Zanidis C, Farsalinos K, Poulas K. 2020. Imiquimod—a toll like receptor 7 agonist—is an ideal option for management of COVID 19. Environ. Res. 188, 109858 (10.1016/j.envres.2020.109858)
    1. Cruz LJ, Rosalia RA, Kleinovink JW, Rueda F, Löwik CW, Ossendorp F. 2014. Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study. J. Control. Release 192, 209–218. (10.1016/j.jconrel.2014.07.040)
    1. Shin MD, et al. 2020. COVID-19 vaccine development and a potential nanomaterial path forward. Nat. Nanotechnol. (10.1038/s41565-020-0737-y)
    1. Choudhury A, Mukherjee S. 2020. In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. J Med. Virol. (10.1002/jmv.25987)
    1. Moreno-Eutimio MA, López-Macías C, Pastelin-Palacios R. 2020. Bioinformatic analysis and identification of single-stranded RNA sequences recognized by TLR7/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. Microbes Infect. 22, 226–229. (10.1016/j.micinf.2020.04.009)
    1. De Wit E, Van Doremalen N, Falzarano D, Munster VJ. 2016. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol. 14, 523 (10.1038/nrmicro.2016.81)
    1. Murakami M, Kamimura D, Hirano T. 2019. Pleiotropy and specificity: insights from the interleukin 6 family of cytokines. Immunity 50, 812–831. (10.1016/j.immuni.2019.03.027)
    1. Wong JJM, Leong JY, Lee JH, Albani S, Yeo JG. 2019. Insights into the immuno-pathogenesis of acute respiratory distress syndrome. Ann. Transl. Med. 7, 504 (10.21037/atm.2019.09.28)
    1. Merad M, Martin JC. 2020. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355–362. (10.1038/s41577-020-0331-4)
    1. Ronco C, Reis T, Husain-Syed F. 2020. Management of acute kidney injury in patients with COVID-19. Lancet Respir. Med. 8, 738–742. (10.1016/S2213-2600(20)30229-0)
    1. Batlle D, Soler MJ, Sparks MA, Hiremath S, South AM, Welling PA, Swaminathan S, Covid, Ace2 in Cardiovascular L, Kidney Working G. 2020. Acute kidney injury in COVID-19: emerging evidence of a distinct pathophysiology. J. Am. Soc. Nephrol. 31, 1380–1383. (10.1681/ASN.2020040419)
    1. Hirsch JS, et al. 2020. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 98, 209–218. (10.1016/j.kint.2020.05.006)
    1. Ng JJ, Luo Y, Phua K, Choong A. 2020. Acute kidney injury in hospitalized patients with coronavirus disease 2019 (COVID-19): a meta-analysis. J. Infect. (10.1016/j.jinf.2020.05.009)
    1. Nechemia-Arbely Y, Barkan D, Pizov G, Shriki A, Rose-John S, Galun E, Axelrod JH. 2008. IL-6/IL-6R axis plays a critical role in acute kidney injury. J. Am. Soc. Nephrol. 19, 1106–1115. (10.1681/ASN.2007070744)
    1. Su H, Lei CT, Zhang C. 2017. Interleukin-6 signaling pathway and its role in kidney disease: an update. Front. Immunol. 8, 405 (10.3389/fimmu.2017.00405)
    1. Jones SA, Fraser DJ, Fielding CA, Jones GW. 2015. Interleukin-6 in renal disease and therapy. Nephrol. Dial. Transplant. 30, 564–574. (10.1093/ndt/gfu233)
    1. Simmons EM, et al. 2004. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int. 65, 1357–1365. (10.1111/j.1523-1755.2004.00512.x)
    1. Horii Y, et al. 1989. Involvement of IL-6 in mesangial proliferative glomerulonephritis. J. Immunol. 143, 3949–3955.
    1. The Lancet Haematology. 2020. COVID-19 coagulopathy: an evolving story. Lancet Haematol. 7, e425 (10.1016/S2352-3026(20)30151-4)
    1. Connors JM, Levy JH. 2020. COVID-19 and its implications for thrombosis and anticoagulation. Blood 135, 2033–2040. (10.1182/blood.2020006000)
    1. Bester J, Pretorius E. 2016. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Scient. Rep. 6, 32188 (10.1038/srep32188)
    1. Menter T, et al. 2020. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 77, 198–209. (10.1111/his.14134)
    1. Petar UDP, et al. 2020. Early initiation of extracorporeal blood purification using the AN69ST (oXiris) hemofilter as a treatment modality for COVID-19 patients: a single-centre case series. Preprint. See (10.21203/-44717/v1)
    1. Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, Pesenti A, Peyvandi F, Tripodi A. 2020. Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. J. Thromb. Haemost. 18, 1738–1742. (10.1111/jth.14850)
    1. USFDA. 2020. Coronavirus treatment acceleration program Silver Spring, MD: USFDA.
    1. Atal S, Fatima Z. 2020. IL-6 inhibitors in the treatment of serious COVID-19: a promising therapy? Pharmaceut. Med. 34, 342 (10.1007/s40290-020-00342-z)
    1. Michot JM, et al. 2020. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann. Oncol. 31, 961–964. (10.1016/j.annonc.2020.03.300)
    1. Maeshima A, Nakasatomi M, Henmi D, Yamashita S, Kaneko Y, Kuroiwa T, Hiromura K, Nojima Y. 2012. Efficacy of tocilizumab, a humanized neutralizing antibody against interleukin-6 receptor, in progressive renal injury associated with Castleman's disease. CEN Case Rep. 1, 7–11. (10.1007/s13730-012-0004-7)
    1. van de Veerdonk FL, Netea MG.. 2020. Blocking IL-1 to prevent respiratory failure in COVID-19. Crit. Care 24, 445 (10.1186/s13054-020-03166-0)
    1. Filocamo G, Mangioni D, Tagliabue P, Aliberti S, Costantino G, Minoia F, Bandera A. 2020. Use of anakinra in severe COVID-19: a case report. Int. J. Infect. Dis. 96, 607–609. (10.1016/j.ijid.2020.05.026)
    1. Cavalli G, et al. 2020. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2, e325–e331. (10.1016/S2665-9913(20)30127-2)
    1. Huet T, et al. 2020. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2, e393-e400. (10.1016/S2665-9913(20)30164-8)
    1. USFDA. 2020. Interleukin-1 inhibitors. Silver Spring, MD: USFDA.
    1. Siegler BH, Brenner T, Uhle F, Weiterer S, Weigand MA, Hofer S. 2016. Why a second look might be worth it: immuno-modulatory therapies in the critically ill patient. J. Thor. Dis. 8, E424–E430. (10.21037/jtd.2016.04.37)
    1. Zeni F, Freeman B, Natanson C. 1997. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit. Care Med. 25, 1095–1100. (10.1097/00003246-199707000-00001)
    1. Cohen J, Carlet J. 1996. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. Crit. Care Med. 24, 1431–1440. (10.1097/00003246-199609000-00002)
    1. Schulte W, Bernhagen J, Bucala R. 2013. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets–an updated view. Mediators Inflamm. 2013, 165974 (10.1155/2013/165974)
    1. Datzmann T, Trager K. 2018. Extracorporeal membrane oxygenation and cytokine adsorption. J. Thoracic Dis. 10, S653­–S660. (10.21037/jtd.2017.10.128)
    1. Rimmele T, Kellum JA. 2011. Clinical review: blood purification for sepsis. Crit. Care 15, 205 (10.1186/cc9411)
    1. Bonavia A, Groff A, Karamchandani K, Singbartl K. 2018. Clinical utility of extracorporeal cytokine hemoadsorption therapy: a literature review. Blood Purif. 46, 337–349. (10.1159/000492379)
    1. Shum HP, Yan WW, Chan TM. 2016. Extracorporeal blood purification for sepsis. Hong Kong Med. J. 22, 478–485. (10.12809/hkmj164876)
    1. Damiani M, Gandini L, Landi F, Fabretti F, Gritti G, Riva I. 2020. Extracorporeal cytokine hemadsorption in severe COVID-19 respiratory failure. medRxiv. 2020.2006.2028.20133561 (10.1101/2020.06.28.20133561)
    1. Liu B, Li M, Zhou Z, Guan X, Xiang Y. 2020. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J. Autoimmun. 111, 102452 (10.1016/j.jaut.2020.102452)
    1. Coomes EA, Haghbayan H. 2020. Interleukin-6 in COVID-19: a systematic review and meta-analysis. medRxiv. 2020.2003.2030.20048058 (10.1101/2020.03.30.20048058)
    1. Zhang Y, Zhong Y, Pan L, Dong J. 2020. Treat 2019 novel coronavirus (COVID-19) with IL-6 inhibitor: are we already that far? Drug Disc. Therapeut. 14, 100–102. (10.5582/ddt.2020.03006)
    1. Feldmann M, Maini RN, Woody JN, Holgate ST, Winter G, Rowland M, Richards D, Hussell T. 2020. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet. 395, 1407–1409. (10.1016/s0140-6736(20)30858-8)
    1. Duret P-M, Sebbag E, Mallick A, Gravier S, Spielmann L, Messer L. 2020. Recovery from COVID-19 in a patient with spondyloarthritis treated with TNF-alpha inhibitor etanercept. Ann. Rheum. Dis. annrheumdis-2020–217362 (10.1136/annrheumdis-2020-217362)

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다