A glance into the Pathology of Covid-19, Its Current and Possible Treatments; Interleukin Antagonists as an Effective Option; A review.
School of Medicine Students' Journal,
Vol. 3 No. 2 (2021),
The outbreak of the novel SARS-COV-2 and its following complications has caused an almost unprecedented chaos throughout the world in recent years. Although a series of vaccines have been proposed recently in order to reduce the risk of mortality and morbidity of this disease, an ultimate and reliable cure has yet to be discovered. One of the major complications of Covid-19 is the outburst of a series of inflammatory responses in the respiratory system of the patients, which eventually causes a hypoxemic pneumonitis and accounts for most of the Covid-19 patients’ mortality. It is suggested that a group of inflammatory cytokines such as different interleukins are responsible for this complication, therefore drugs which can influence this system may be useful in reducing this exaggerated inflammatory response which is dubbed the ‘cytokine storm’. In this article we review potential treatment options for reducing the inflammatory response and discuss some clinical trials and case reports related to the drugs interfering with responsible interleukins in order to quench the cytokine storm.
- cytokine release syndrome
How to Cite
Organization WH.COVID-19 weekly epidemiological update, edition 45, 22 June 2021. available :https://apps.who.int/iris/bitstream/handle/10665/342009/CoV-weekly-sitrep22Jun21-eng.pdf?sequence=1accessed 30.6.2021 2021.
Tregoning JS, Brown ES, Cheeseman HM, Flight KE, Higham SL, Lemm NM, et al.Vaccines for COVID‐19.Clinical & Experimental Immunology.2020;202(2):162-92.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The lancet.2020;395(10223):497-506.
Polidoro RB, Hagan RS, de Santis Santiago R and Schmidt NW.Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19.Frontiers in Immunology.2020;11:1626.
Ruan Q, Yang K, Wang W, Jiang L and Song J.Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.Intensive care medicine.2020;46(5):846-48.
Antony SJ, Davis MA, Davis MG, Almaghlouth NK, Guevara R, Omar F, et al.Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management.Journal of Medical Virology.2020.
Antwi‐Amoabeng D, Kanji Z, Ford B, Beutler BD, Riddle MS and Siddiqui F.Clinical Outcomes in COVID‐19 Patients Treated with Tocilizumab: An Individual Patient Data Systematic Review.Journal of Medical Virology.2020.
Biran N, Ip A, Ahn J, Go RC, Wang S, Mathura S, et al.Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.The Lancet Rheumatology.2020.
Canziani LM, Trovati S, Brunetta E, Testa A, De Santis M, Bombardieri E, et al.Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.Journal of autoimmunity.2020:102511.
Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, et al.Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.The Lancet Rheumatology.2020.
Snijder E, Decroly E and Ziebuhr J.The nonstructural proteins directing coronavirus RNA synthesis and processing.Advances in virus research.2016;96:59-126.
Hu B, Huang S and Yin L.The cytokine storm and COVID‐19.Journal of medical virology.2020.
Ahmed SF, Quadeer AA and McKay MR.Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies.Viruses.2020;12(3):254.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al.Pathological findings of COVID-19 associated with acute respiratory distress syndrome.The Lancet respiratory medicine.2020;8(4):420-22.
Zhang H, Zhou P, Wei Y, Yue H, Wang Y, Hu M, et al.Histopathologic changes and SARS-CoV-2 immunostaining in the lung of a patient with COVID-19.Annals of internal medicine.2020;172(9):629-32.
Arastehfar A, Carvalho A, van de Veerdonk FL, Jenks JD, Koehler P, Krause R, et al.COVID-19 associated pulmonary aspergillosis (CAPA)—from immunology to treatment.Journal of Fungi.2020;6(2):91.
Butler DJ, Mozsary C, Meydan C, Danko D, Foox J, Rosiene J, et al.Shotgun transcriptome and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.bioRxiv.2020.
Glowacka I, Bertram S, Herzog P, Pfefferle S, Steffen I, Muench MO, et al.Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63.Journal of virology.2010;84(2):1198-205.
Tolouian R, Vahed SZ, Ghiyasvand S, Tolouian A and Ardalan M.COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment.Journal of Renal Injury Prevention.2020;9(2):e19-e19.
Roshanravan N, Seif F, Ostadrahimi A, Pouraghaei M and Ghaffari S.Targeting cytokine storm to manage patients with COVID-19: a mini-review.Archives of Medical Research.2020.
Sun X, Wang T, Cai D, Hu Z, Liao H, Zhi L, et al.Cytokine storm intervention in the early stages of COVID-19 pneumonia.Cytokine & Growth Factor Reviews.2020 ;53:38-42.
Liu Z, Li J, Chen D, Gao R, Zeng W, Chen S, et al.Dynamic Interleukin-6 Level Changes as a Prognostic Indicator in Patients With COVID-19.Frontiers in Pharmacology.2020;11:1093.
Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al.The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China.Clinical Immunology.2020:108393.
Prete M, Favoino E, Catacchio G, Racanelli V and Perosa F.SARS-CoV-2 infection complicated by inflammatory syndrome. Could high-dose human immunoglobulin for intravenous use (IVIG) be beneficial?Autoimmunity Reviews.2020 ;19(7):102559.
Quartuccio L, Semerano L, Benucci M, Boissier M-C and De Vita S.Urgent avenues in the treatment of COVID-19: Targeting downstream inflammation to prevent catastrophic syndrome.Joint Bone Spine.2020;87(3):191.
Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y and Forthal DN.Pharmaco-immunomodulatory therapy in COVID-19.Drugs.2020:1-26.
Robertson CE.Could CGRP antagonists be helpful in the fight against COVID‐19?Headache: The Journal of Head and Face Pain.2020.
Rodrigues‐Diez RR, Tejera‐Muñoz A, Marquez‐Exposito L, Rayego‐Mateos S, Santos Sanchez L, Marchant V, et al.Statins: Could an old friend help in the fight against COVID‐19?British Journal of Pharmacology.2020 ;177(21):4873-86.
He Y, Hara H and Núñez G.Mechanism and regulation of NLRP3 inflammasome activation.Trends in biochemical sciences.2016;41(12):1012-21.
Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, et al.Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.Critical care medicine.2005;33(1):226-29.
Tulgar S, Ahıskalıoğlu A, Kök A and Thomas DT.Possible Old Drugs for Repositioning in COVID-19 Treatment: Combating Cytokine Storms from Haloperidol to Anti-interleukin Agents.Turk J Anaesthesiol Reanim.2020;48(3):256-57.
Mendoza VMM.Interleukin-17: a potential therapeutic target in COVID-19.Journal of Infection.2020.
KURZROCK R and Kato S.Repurposing Interleukin-6 Inhibitors to Combat COVID-19.2020.
Liu B, Li M, Zhou Z, Guan X and Xiang Y.Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?Journal of Autoimmunity.2020:102452.
Bulat V, Situm M, Azdajic MD and Likic R.Potential role of IL‐17 blocking agents in the treatment of severe COVID‐19?British Journal of Clinical Pharmacology.2020.
Luo W, Li Y-X, Jiang L-J, Chen Q, Wang T and Ye D-W.Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19.Trends in Pharmacological Sciences.2020 ;41(8):531-43.
Kato S and Kurzrock R.Repurposing Interleukin-6 Inhibitors to Combat COVID-19.Journal of Immunotherapy and Precision Oncology.2020;3(2):52-55.
Franzetti M, Pozzetti U, Carugati M, Pandolfo A, Molteni C, Faccioli P, et al.Interleukin-1 receptor antagonist anakinra in association with remdesivir in severe Coronavirus disease 2019: A case report.International Journal of Infectious Diseases.2020.
Sheng CC, Sahoo D, Dugar S, Prada RA, Wang TKM, Abou Hassan OK, et al.Canakinumab to reduce deterioration of cardiac and respiratory function in SARS‐CoV‐2 associated myocardial injury with heightened inflammation (canakinumab in Covid‐19 cardiac injury: The three C study).Clinical cardiology.2020 ;43(10):1055-63.
Conti P, Caraffa A, Gallenga C, Ross R, Kritas S, Frydas I, et al.IL-1 induces throboxane-A2 (TxA2) in COVID-19 causing inflammation and micro-thrombi: inhibitory effect of the IL-1 receptor antagonist (IL-1Ra).Journal of biological regulators and homeostatic agents.2020;34(4).
Rohilla S.Designing therapeutic strategies to combat severe acute respiratory syndrome coronavirus‐2 disease: COVID‐19.Drug Development Research.2020 ;82(1):12-26.
Sinha P, Mostaghim A, Bielick CG, McLaughlin A, Hamer DH, Wetzler LM, et al.Early administration of Interleukin-6 inhibitors for patients with severe Covid-19 disease is associated with decreased intubation, reduced mortality, and increased discharge.International Journal of Infectious Diseases.2020;99:28-33.
Rossotti R, Travi G, Ughi N, Corradin M, Baiguera C, Fumagalli R, et al.Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: a comparative analysis.Journal of Infection.2020;81(4):e11-e17.
Klopfenstein T, Zayet S, Lohse A, Balblanc J-C, Badie J, Royer P-Y, et al.Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients.Médecine et Maladies Infectieuses.2020 ;50(5):397-400.
Maeda T, Obata R, Rizk DO D and Kuno T.The Association of Interleukin‐6 value, Interleukin inhibitors and Outcomes of Patients with COVID‐19 in New York City.Journal of medical virology.2020.
Dastan F, Saffaei A, Haseli S, Marjani M, Moniri A, Abtahian Z, et al.Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.International immunopharmacology.2020;88:106869.
Conrozier T, Lohse A, Balblanc J-C, Dussert P, Royer P-Y, Bossert M, et al.Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.Clin Exp Rheumatol.2020;38:742-47.
Luo P, Liu Y, Qiu L, Liu X, Liu D and Li J.Tocilizumab treatment in COVID‐19: A single center experience.Journal of medical virology.2020;92(7):814-18.
Radbel J, Narayanan N and Bhatt PJ.Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report.Chest.2020.
Aouba A, Baldolli A, Geffray L, Verdon R, Bergot E, Martin-Silva N, et al.Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series.Annals of the Rheumatic Diseases.2020 ;79(10):1381-82.
Navarro‐Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH and Crow MK.Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID‐19: A Case Series.Arthritis & Rheumatology.2020.
Villegas C, Poza M, Talayero P, Teller JMC, Zafra D, Garcia C, et al.IL-1R blockade is not effective in patients with hematological malignancies and severe SARS-CoV-2 infection.Annals of hematology.2020:1-4.
González-García A, García-Sánchez I, Lopes V, Moreno-Arrones OM, Tortosa-Cabañas M, Elías-Sáenz I, et al.Successful treatment of severe COVID-19 with subcutaneous anakinra as a sole treatment.Rheumatology.2020;59(8):2171-73.
Karadeniz H, Yamak BA, Özger HS, Sezenöz B, Tufan A and Emmi G.Anakinra for the Treatment of COVID-19-Associated Pericarditis: A Case Report.Cardiovascular Drugs and Therapy.2020:1-3.
Landi L, Ravaglia C, Russo E, Cataleta P, Fusari M, Boschi A, et al.Blockage of interleukin-1β with canakinumab in patients with Covid-19.Scientific reports.2020;10(1):1-9.
Generali D, Bosio G, Malberti F, Cuzzoli A, Testa S, Romanini L, et al.Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study.International Journal of Infectious Diseases.2021;104:433-40.
Katia F, Myriam DP, Ucciferri C, Auricchio A, Di Nicola M, Marchioni M, et al.Efficacy of canakinumab in mild or severe COVID‐19 pneumonia.Immunity, Inflammation and Disease.2021 ;9(2):399-405.
Ucciferri C, Auricchio A, Di Nicola M, Potere N, Abbate A, Cipollone F, et al.Canakinumab in a subgroup of patients with COVID-19.The Lancet Rheumatology.2020.
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