Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context

Letter Virology

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

Jieyun Zhu et al.

JOURNAL OF MEDICAL VIROLOGY (2021)

Article Medicine, General & Internal

Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

Shruti Gupta et al.

Summary: A multicenter cohort study found that early treatment with tocilizumab may reduce mortality among critically ill patients with COVID-19. Further research from randomized clinical trials is needed to confirm these findings.

JAMA INTERNAL MEDICINE (2021)

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Article Medicine, General & Internal

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia A Randomized Clinical Trial

Olivier Hermine et al.

Summary: In this clinical trial of COVID-19 patients with pneumonia requiring oxygen support but not in the ICU, tocilizumab did not reduce WHO-CPS scores below 5 by day 4 but may have reduced the risk of needing noninvasive ventilation, mechanical ventilation, or death by day 14. There was no difference in mortality by day 28. Further studies are needed to confirm these preliminary results.

JAMA INTERNAL MEDICINE (2021)

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Article Medicine, General & Internal

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia A Randomized Clinical Trial

Carlo Salvarani et al.

Summary: This study evaluated the use of tocilizumab in hospitalized COVID-19 pneumonia patients and found no significant benefit compared to standard care. Further randomized clinical trials with blinded, placebo-controlled methods are needed to confirm these results and explore potential applications of tocilizumab in different stages of the disease.

JAMA INTERNAL MEDICINE (2021)

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Editorial Material Medicine, General & Internal

Time to Reassess Tocilizumab's Role in COVID-19 Pneumonia

Jonathan B. Parr

JAMA INTERNAL MEDICINE (2021)

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Article Critical Care Medicine

Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation A Meta-analysis

Zheng Jie Lim et al.

Summary: The study indicates that the case fatality rate of COVID-19 patients receiving invasive mechanical ventilation is around 45%, but varying reporting methods result in a wide range of fatality rates across studies. Fatality rates are higher in older patients and in early pandemic epicenters.

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2021)

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Article Medicine, General & Internal

Anti-IL6 treatment of serious COVID-19 disease A monocentric retrospective experience

Laura Castelnovo et al.

Summary: Tocilizumab and sarilumab may be effective in treating COVID-19 pneumonia, reducing mortality rates. Anti-IL6 drugs can decrease inflammation levels, shorten hospitalization times, and reduce the risk of death from multi-organ failure. However, further research is needed to determine the optimal treatment timing.

MEDICINE (2021)

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Article Medicine, General & Internal

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

Carlos Salama et al.

Summary: Among hospitalized patients with Covid-19 pneumonia not on mechanical ventilation, tocilizumab reduced the risk of progression to mechanical ventilation or death, but did not improve overall survival. There were no new safety concerns identified.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Medicine, General & Internal

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

Viviane C. Veiga et al.

Summary: The study found that in patients with severe or critical COVID-19, tocilizumab in combination with standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.

BMJ-BRITISH MEDICAL JOURNAL (2021)

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Article Critical Care Medicine

Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study

Lionel Piroth et al.

Summary: Patients hospitalized for COVID-19 and influenza in France showed significant differences in terms of hospitalization requirements, clinical characteristics, and outcomes, with COVID-19 patients more likely to develop severe complications and have higher mortality rates. In children, while hospitalization rate for COVID-19 appeared lower than for influenza, in-hospital mortality was higher, although limited by low patient numbers. These findings emphasize the need for appropriate preventive measures, specific vaccines, and treatments for COVID-19.

LANCET RESPIRATORY MEDICINE (2021)

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Article Medicine, General & Internal

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

I. O. Rosas et al.

Summary: In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Medicine, General & Internal

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Anthony C. Gordon et al.

Summary: Interleukin-6 receptor antagonists tocilizumab and sarilumab were found to improve outcomes, including survival, in critically ill patients with Covid-19 receiving organ support in ICUs according to an ongoing international trial. The efficacy of these treatments has been confirmed, with patients benefiting from the therapy.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Critical Care Medicine

Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making?

Christopher J. Yarnell et al.

Summary: Recent Bayesian reanalyses of prominent trials in critical illness have generated controversy by contradicting the initial conclusions based on conventional frequentist analyses. In most cases, Bayesian and frequentist analyses agreed, but Bayesian analysis identified interventions where benefit was probable despite the absence of statistical significance. Bayesian analysis in critical care medicine can help to distinguish harm from uncertainty and establish the probability of clinically important benefit for clinicians, policy makers, and patients.

LANCET RESPIRATORY MEDICINE (2021)

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Editorial Material Critical Care Medicine

IL-6 blockade for COVID-19: a global scientific call to arms

Srinivas Murthy et al.

LANCET RESPIRATORY MEDICINE (2021)

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Article Critical Care Medicine

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Francois-Xavier Lescure et al.

Summary: This study aimed to evaluate the safety and efficacy of sarilumab in patients with severe or critical COVID-19, but found no significant efficacy in patients admitted to the hospital receiving supplemental oxygen. Future adequately powered trials of targeted immunomodulatory therapies with survival as a primary endpoint are suggested for patients with critical COVID-19.

LANCET RESPIRATORY MEDICINE (2021)

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Article Critical Care Medicine

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open- label, multicentre, randomised, controlled, phase 3 trial

Arvinder S. Soin et al.

Summary: The study recruited 180 patients and found that tocilizumab did not reduce disease progression in patients with moderate to severe COVID-19, but may have some effect in severe cases.

LANCET RESPIRATORY MEDICINE (2021)

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Review Critical Care Medicine

Interleukin-6: obstacles to targeting a complex cytokine in critical illness

Oliver J. McElvaney et al.

Summary: IL-6 is a pleiotropic cytokine that plays a dual role in both inflammation and anti-inflammatory functions. Understanding the complex signaling processes of IL-6 is crucial for accurately interpreting its concentrations in blood or lungs, utilizing it as a critical care biomarker, and designing effective anti-IL-6 strategies.

LANCET RESPIRATORY MEDICINE (2021)

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Article Hematology

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Ning Tang et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2020)

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Article Medicine, General & Internal

A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Allergy

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

Tobias Herold et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2020)

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Article Hematology

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

Jecko Thachil et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2020)

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Article Medicine, General & Internal

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

Fei Zhou et al.

LANCET (2020)

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Article Rheumatology

Translating IL-6 biology into effective treatments

Ernest H. Choy et al.

NATURE REVIEWS RHEUMATOLOGY (2020)

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Article Medicine, General & Internal

Remdesivir for the Treatment of Covid-19-Final Report

John H. Beigel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Medicine, General & Internal

Mild or Moderate Covid-19

Rajesh T. Gandhi et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Critical Care Medicine

Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019 Survival and Clinical Outcomes

Christina C. Price et al.

CHEST (2020)

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Article Critical Care Medicine

COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?

Eddy Fan et al.

LANCET RESPIRATORY MEDICINE (2020)

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Review Medicine, General & Internal

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

W. Joost Wiersinga et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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Review Medicine, General & Internal

COVID-19 length of hospital stay: a systematic review and data synthesis

Eleanor M. Rees et al.

BMC MEDICINE (2020)

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Article Biochemistry & Molecular Biology

An inflammatory cytokine signature predicts COVID-19 severity and survival

Diane Marie Del Valle et al.

NATURE MEDICINE (2020)

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Article Biochemistry & Molecular Biology

A dynamic COVID-19 immune signature includes associations with poor prognosis

Adam G. Laing et al.

NATURE MEDICINE (2020)

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Article Medicine, General & Internal

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

John H. Stone et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Multidisciplinary Sciences

Preemptive interleukin-6 blockade in patients with COVID-19

Lucia Guillen et al.

SCIENTIFIC REPORTS (2020)

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Review Critical Care Medicine

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

Daniel E. Leisman et al.

LANCET RESPIRATORY MEDICINE (2020)

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Article Biochemistry & Molecular Biology

High serum IL-6 values increase the risk of mortality and the severity of pneumonia in patients diagnosed with COVID-19

Jose J. Guirao et al.

MOLECULAR IMMUNOLOGY (2020)

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Review Medicine, General & Internal

Cytokine Storm

David C. Fajgenbaum et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Ethics

Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature

Clarissa F. D. Carneiro et al.

RESEARCH INTEGRITY AND PEER REVIEW (2020)

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Article Pharmacology & Pharmacy

The effect of tocilizumab on cytokine release syndrome in COVID-19 patients

Carmen de Caceres et al.

PHARMACOLOGICAL REPORTS (2020)

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Article Rheumatology

COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study

Jessica J. Manson et al.

LANCET RHEUMATOLOGY (2020)

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Article Rheumatology

Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study

Noa Biran et al.

LANCET RHEUMATOLOGY (2020)

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Article Mathematical & Computational Biology

Randomised trials with provision for early stopping for benefit (or harm): The impact on the estimated treatment effect

S. D. Walter et al.

STATISTICS IN MEDICINE (2019)

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Review Critical Care Medicine

Defining standard of practice: pros and cons of the usual care arm

Federico Angriman et al.

CURRENT OPINION IN CRITICAL CARE (2019)

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Review Biotechnology & Applied Microbiology

Interleukin-6: designing specific therapeutics for a complex cytokine

Christoph Garbers et al.

NATURE REVIEWS DRUG DISCOVERY (2018)

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Article Health Care Sciences & Services

Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses

Miguel A. Hernan et al.

JOURNAL OF CLINICAL EPIDEMIOLOGY (2016)

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Review Medicine, General & Internal

Rheumatoid arthritis

Josef S. Smolen et al.

LANCET (2016)

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Review Medicine, General & Internal

Adaptive Designs for Clinical Trials

Deepak L. Bhatt et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

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Review Rheumatology

Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement

Monika M. Schoels et al.

ANNALS OF THE RHEUMATIC DISEASES (2013)

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Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context

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