The role of IL-6 and IL-6 blockade in COVID-19

Anti-IL6 treatment of serious COVID-19 disease

(2021) Laura Castelnovo et al.   MEDICINE

Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia

(2021) Rogan A. Grant et al.   NATURE

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial

(2021) Viviane C Veiga et al.   BMJ-British Medical Journal

Clinical course of severe patients with COVID-19 treated with tocilizumab: report from a cohort study in Spain

(2021) Esther Chamorro-de-Vega et al.   Expert Review of Clinical Pharmacology

The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials

(2021) Chia Siang Kow et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID‐19 patients treated with tocilizumab

(2021) Rania M Sarhan et al.   INTERNATIONAL JOURNAL OF CLINICAL PRACTICE

Tocilizumab in COVID‐19 interstitial pneumonia

(2021) G. Pomponio et al.   JOURNAL OF INTERNAL MEDICINE

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

(2020) Qiurong Ruan et al.   INTENSIVE CARE MEDICINE

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

(2020) Chaolin Huang et al.   LANCET

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

(2020) Zhe Xu et al.   Lancet Respiratory Medicine

Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients

(2020) Pierre Bost et al.   CELL

Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

(2020) Evangelos J. Giamarellos-Bourboulis et al.   Cell Host & Microbe

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

(2020) Xiaohua Chen et al.   CLINICAL INFECTIOUS DISEASES

Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China

(2020) Chuan Qin et al.   CLINICAL INFECTIOUS DISEASES

IL-6: Relevance for immunopathology of SARS-CoV-2

(2020) E.O. Gubernatorova et al.   CYTOKINE & GROWTH FACTOR REVIEWS

The role of interleukin‐6 in monitoring severe case of coronavirus disease 2019

(2020) Tao Liu et al.   EMBO Molecular Medicine

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

(2020) Ruggero Capra et al.   European Journal of Internal Medicine

Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study

(2020) Corrado Campochiaro et al.   European Journal of Internal Medicine

Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

(2020) Tobias Herold et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Clinical and immunological features of severe and moderate coronavirus disease 2019

(2020) Guang Chen et al.   JOURNAL OF CLINICAL INVESTIGATION

SARS-CoV-2: a storm is raging

(2020) Savannah F. Pedersen et al.   JOURNAL OF CLINICAL INVESTIGATION

Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care

(2020) Luca Quartuccio et al.   JOURNAL OF CLINICAL VIROLOGY

Historical overview of the interleukin-6 family cytokine

(2020) Sujin Kang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal

(2020) Hasan K. Siddiqi et al.   JOURNAL OF HEART AND LUNG TRANSPLANTATION

COVID‐19 pneumonia treated with Sarilumab: a clinical series of eight patients

(2020) Maurizio Benucci et al.   JOURNAL OF MEDICAL VIROLOGY

Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis

(2020) Jieyun Zhu et al.   JOURNAL OF MEDICAL VIROLOGY

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

(2020) Matthew J Cummings et al.   LANCET

Endothelial cell infection and endotheliitis in COVID-19

(2020) Zsuzsanna Varga et al.   LANCET

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

(2020) Fei Zhou et al.   LANCET

COVID-19: consider cytokine storm syndromes and immunosuppression

(2020) Puja Mehta et al.   LANCET

Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19

(2020) Mingfeng Liao et al.   NATURE MEDICINE

Translating IL-6 biology into effective treatments

(2020) Ernest H. Choy et al.   Nature Reviews Rheumatology

Effective treatment of severe COVID-19 patients with tocilizumab

(2020) Xiaoling Xu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

(2020) Bo Diao et al.   Frontiers in Immunology

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

(2020) Jing Liu et al.   EBioMedicine

Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study

(2020) Emanuel Della-Torre et al.   ANNALS OF THE RHEUMATIC DISEASES

Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case–control study

(2020) Nicola Potere et al.   ANNALS OF THE RHEUMATIC DISEASES

The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications

(2020) James D. McFadyen et al.   CIRCULATION RESEARCH

Early administration of Interleukin-6 inhibitors for patients with severe Covid-19 disease is associated with decreased intubation, reduced mortality, and increased discharge

(2020) Pranay Sinha et al.   INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Mild versus severe COVID-19: Laboratory markers

(2020) Thirumalaisamy P. Velavan et al.   INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Low-Dose Subcutaneous Tocilizumab to Prevent Disease Progression in Patients with Moderate COVID-19 Pneumonia and Hyperinflammation

(2020) Nicola Potere et al.   INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

(2020) W. Joost Wiersinga et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

IL-6–based mortality risk model for hospitalized patients with COVID-19

(2020) Rocio Laguna-Goya et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness

(2020) Fenghe Du et al.   JOURNAL OF THROMBOSIS AND THROMBOLYSIS

Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial

(2020) Bastiaan Maes et al.   Trials

Is a “Cytokine Storm” Relevant to COVID-19?

(2020) Pratik Sinha et al.   JAMA Internal Medicine

Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies

(2020) Aldo Bonaventura et al.   Frontiers in Immunology

Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

(2020) Rafael B. Polidoro et al.   Frontiers in Immunology

Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies

(2020) Meng Zhao et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Inflammasome formation in the lungs of patients with fatal COVID-19

(2020) Stefano Toldo et al.   INFLAMMATION RESEARCH

Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions

(2020) Matthijs Kox et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection

(2020) Ana Copaescu et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

IL‐18 and infections: Is there a role for targeted therapies?

(2020) Alessandra Vecchié et al.   JOURNAL OF CELLULAR PHYSIOLOGY

The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics

(2020) Mitra Abbasifard et al.   LIFE SCIENCES

Characteristics of SARS-CoV-2 and COVID-19

(2020) Ben Hu et al.   NATURE REVIEWS MICROBIOLOGY

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

(2020) John H. Stone et al.   NEW ENGLAND JOURNAL OF MEDICINE

Interleukin‐6 in Covid‐19: A systematic review and meta‐analysis

(2020) Eric A. Coomes et al.   REVIEWS IN MEDICAL VIROLOGY

Observational study on off-label use of tocilizumab in patients with severe COVID-19

(2020) Laetitia Albertini et al.   European Journal of Hospital Pharmacy-Science and Practice

Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes

(2020) Daniel E Leisman et al.   Lancet Respiratory Medicine

Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study

(2020) Mar Masiá et al.   EBioMedicine

Interleukin-6 receptor blockade with subcutaneous tocilizumab improves coagulation activity in patients with COVID-19

(2020) Marcello Di Nisio et al.   European Journal of Internal Medicine

Coronavirus disease 2019: investigational therapies in the prevention and treatment of hyperinflammation

(2020) Isabelle Amigues et al.   Expert Review of Clinical Immunology

Natural history of COVID-19 and therapeutic options

(2020) Philippe Gautret et al.   Expert Review of Clinical Immunology

Defining IL‐6 levels in healthy individuals: A meta‐analysis

(2020) Elias A. Said et al.   JOURNAL OF MEDICAL VIROLOGY

Association of elevated inflammatory markers and severe COVID-19

(2020) Pan Ji et al.   MEDICINE

Cytokine Storm

(2020) David C. Fajgenbaum et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

(2020) Carlos Salama et al.   NEW ENGLAND JOURNAL OF MEDICINE

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome

(2020) Laura Pandolfi et al.   BMC Pulmonary Medicine

SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells

(2020) Tapas Patra et al.   PLoS Pathogens

Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation: A Comprehensive Review of Available and Emerging Evidence at the Peak of the Pandemic

(2020) Giulio Cavalli et al.   Frontiers in Pharmacology

International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

(2020) Frits van Rhee et al.   Blood Advances

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

(2020) Varvara A. Ryabkova et al.   CLINICAL IMMUNOLOGY

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

(2020) Imad M. Tleyjeh et al.   CLINICAL MICROBIOLOGY AND INFECTION

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

(2019) Stephanie Finzel et al.   ANNALS OF THE RHEUMATIC DISEASES

Treatment and outcome of Unicentric Castleman Disease: a retrospective analysis of 71 cases

(2019) David Boutboul et al.   BRITISH JOURNAL OF HAEMATOLOGY

Sarilumab: Review of a Second IL-6 Receptor Antagonist Indicated for the Treatment of Rheumatoid Arthritis

(2018) Eric G. Boyce et al.   ANNALS OF PHARMACOTHERAPY

Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study

(2018) Peter C Taylor et al.   ANNALS OF THE RHEUMATIC DISEASES

IL-6 family cytokines: Key inflammatory mediators as biomarkers and potential therapeutic targets

(2018) Nese Unver et al.   CYTOKINE & GROWTH FACTOR REVIEWS

FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell‐Induced Severe or Life‐Threatening Cytokine Release Syndrome

(2018) Robert Q. Le et al.   ONCOLOGIST

Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab

(2018) Joel M. Kremer et al.   Arthritis & Rheumatology

Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

(2018) Yuko Kaneko et al.   ANNALS OF THE RHEUMATIC DISEASES

Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study

(2017) Daniel Aletaha et al.   LANCET

Trial of Tocilizumab in Giant-Cell Arteritis

(2017) John H. Stone et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tocilizumab (Actemra)

(2017) Martin Sheppard et al.   Human Vaccines & Immunotherapeutics

Sarilumab and Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors

(2017) Roy Fleischmann et al.   Arthritis & Rheumatology

Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update

(2017) Hua Su et al.   Frontiers in Immunology

Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

(2016) Gerd R Burmester et al.   ANNALS OF THE RHEUMATIC DISEASES

Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial

(2016) Daniel J Wallace et al.   ANNALS OF THE RHEUMATIC DISEASES

Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Methotrexate- and Biologic-naive or Free of Methotrexate for 6 Months: the AMBITION Study

(2016) Graeme Jones et al.   JOURNAL OF RHEUMATOLOGY

Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

(2016) Peter M Villiger et al.   LANCET

Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial

(2016) Dinesh Khanna et al.   LANCET

The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis

(2016) Philip J. Mease et al.   Arthritis & Rheumatology

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis

(2016) Brad H. Rovin et al.   Arthritis & Rheumatology

Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial

(2015) Tsutomu Takeuchi et al.   Modern Rheumatology

Catch-Up Growth During Tocilizumab Therapy for Systemic Juvenile Idiopathic Arthritis: Results From a Phase III Trial

(2015) Fabrizio De Benedetti et al.   Arthritis & Rheumatology

Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study

(2014) Mark C Genovese et al.   ANNALS OF THE RHEUMATIC DISEASES

Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)

(2014) Joachim Sieper et al.   ANNALS OF THE RHEUMATIC DISEASES

Regulation of IL-6-type cytokine responses by MAPKs: Figure 1

(2014) Ana P. Costa-Pereira   BIOCHEMICAL SOCIETY TRANSACTIONS

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma

(2014) J. San-Miguel et al.   BLOOD

Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial

(2014) Frits van Rhee et al.   LANCET ONCOLOGY

IL-6 in Inflammation, Immunity, and Disease

(2014) T. Tanaka et al.   Cold Spring Harbor Perspectives in Biology

Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials

(2013) Joachim Sieper et al.   ANNALS OF THE RHEUMATIC DISEASES

Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis

(2013) José Ramón Lamas et al.   CYTOKINE

Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial

(2013) Cem Gabay et al.   LANCET

Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus

(2012) Yuko Shirota et al.   ANNALS OF THE RHEUMATIC DISEASES

B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1

(2012) Alex Karnowski et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Into the Eye of the Cytokine Storm

(2012) J. R. Tisoncik et al.   MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS

Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients--REACTION 52-week study

(2011) T. Takeuchi et al.   RHEUMATOLOGY

Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: Results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structu

(2010) Joel M. Kremer et al.   ARTHRITIS AND RHEUMATISM

Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study

(2009) G. Jones et al.   ANNALS OF THE RHEUMATIC DISEASES

IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial

(2008) P. Emery et al.   ANNALS OF THE RHEUMATIC DISEASES

Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study

(2008) Mark C. Genovese et al.   ARTHRITIS AND RHEUMATISM

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial

(2008) Josef S Smolen et al.   LANCET

Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial

(2008) Shumpei Yokota et al.   LANCET