Severe <scp>COVID</scp>‐19 and interleukin‐6 receptor antagonist tocilizumab: Some notes of concern

Akinosoglou, Karolina; Gogos, Charalambos

doi:10.1111/resp.13939

Cited by 5 publications

(4 citation statements)

References 7 publications

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“… 93 , 94 The main concern is that some believe this agent can diminish short‐term mortality at the expense of increasing long‐term mortality. 95 Other adverse events that are likely following tocilizumab therapy include LFTs elevation, absolute neutrophil count (ANC) and a reduction of platelets, infusion‐related adverse reactions, anaphylaxis, acute hypertriglyceridemia, ‏increased risk of latent TB reactivation, hepatitis B virus (HBV) reactivation, complications of the hepatitis C virus (HCV), hypotension, gastrointestinal (GI) perforation, and dyspnoea. 96 , 97 , 98 , 99 , 100 , 101 Recently, medication‐related osteonecrosis of the jaw (MRONJ) was identified as a rare complication of tocilizumab therapy.…”

Section: Safety Issues To Be Considered During Tocilizumab Therapymentioning

confidence: 99%

“…The most concerning issue in applying tocilizumab has been the increased risk of bacterial and fungal superinfections, particularly in critically ill COVID‐19 patients in an ICU, due to its innate immunity weakening properties 93,94 . The main concern is that some believe this agent can diminish short‐term mortality at the expense of increasing long‐term mortality 95 . Other adverse events that are likely following tocilizumab therapy include LFTs elevation, absolute neutrophil count (ANC) and a reduction of platelets, infusion‐related adverse reactions, anaphylaxis, acute hypertriglyceridemia, ‏increased risk of latent TB reactivation, hepatitis B virus (HBV) reactivation, complications of the hepatitis C virus (HCV), hypotension, gastrointestinal (GI) perforation, and dyspnoea 96–101 .…”

Section: Safety Issues To Be Considered During Tocilizumab Therapymentioning

confidence: 99%

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The role of cytokines and their antagonists in the treatment of COVID‐19 patients

Afshar

Barary

Babazadeh

et al. 2022

Reviews in Medical Virology

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The coronavirus disease 2019 (COVID‐19) has various presentations, of which immune dysregulation or the so‐called cytokine storm syndrome (COVID‐CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID‐19 infections, caused by the excessive release of pro‐inflammatory cytokines, such as interleukin‐1 (IL‐1), IL‐6, IL‐8, tumour necrosis factor, granulocyte‐macrophage colony‐stimulating factor, and interferon‐gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin‐6 receptor blocker approved to treat severe COVID‐19 infections.

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Section: Safety Issues To Be Considered During Tocilizumab Therapymentioning

confidence: 99%

Section: Safety Issues To Be Considered During Tocilizumab Therapymentioning

confidence: 99%

The role of cytokines and their antagonists in the treatment of COVID‐19 patients

Afshar

Barary

Babazadeh

et al. 2022

Reviews in Medical Virology

View full text Add to dashboard Cite

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“…In the case of COVID-19 patients with severe pneumonia and ARDS, elevated serum levels of the inflammatory cytokine IL-6 were a marker for poor outcomes. Several clinical trials (NCT04317092, NCT04320615, and NCT04370834) are currently under evaluation in many countries (Italy, USA, and China) to evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of the IL-6 receptor-targeted mAb tocilizumab to dampen the inflammatory response in patients with severe COVID-19 [69][70][71][72][73]. Another potential target of COVID-19 immunomodulatory mAb therapy is the inflammatory cytokine IL-1β, which plays an essential role in the cytokine storm associated with SARS-CoV-2 infection [74].…”

Section: Sars-cov-2 Immunomodulatory Antibody-based Therapeuticsmentioning

confidence: 99%

Antibody-Based Immunotherapeutic Strategies for COVID-19

et al. 2020

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Global efforts to contain the coronavirus disease-2019 (COVID-19) include the development of novel preventive vaccines and effective therapeutics. Passive antibody therapies using convalescent plasma, SARS-CoV-2 (Severe-Acute-Respiratory-Syndrome-Corona-Virus-2)-specific neutralizing antibodies (NAbs), and the development of monoclonal antibodies (MAbs) are among the most promising strategies for prophylaxis and treatment of SARS-CoV-2 infections. In addition, several immunomodulatory antibodies acting via several mechanisms to boost the host immune defense against SARS-CoV-2 infection as well as to avoid the harmful overreaction of the immune system are currently under clinical trial. Our main objective is to present the current most up-to-date progress in some clinical trials registered at ClinicalTrials.gov. We highlight the pros and pitfalls of several SARS-CoV-2 antibody-based immunotherapeutics.

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“…[2,7] The use of immunosuppressive drugs such as systemic corticosteroids and antiinterleukin 6 receptor monoclonal antibodies further suppress the immunity. [8][9][10][11][12] Thus, patients with severe COVID-19 are likely to have a sustained immune-paralytic state after the initial pro-inflammatory state, similar to Gram-negative sepsis. [3] Interestingly, those who recover mount a Th1 predominant response than the historical controls with non-COVID infection.…”

Section: Introductionmentioning

confidence: 99%

A randomised trial of Mycobacterium w in critically ill patients with COVID-19: ARMY-1

et al. 2021

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PurposeWe investigate whether Mycobacterium w (Mw), an immunomodulator, would improve clinical outcomes in coronavirus infectious disease 19 (COVID-19).MethodsWe conducted an exploratory, randomised, double-blind, placebo-controlled trial of hospitalised subjects with severe COVID-19 (pulmonary infiltrates and oxygen saturation ≤94% on room air) conducted at four tertiary care centers in India. Patients were randomised 1:1 to receive either 0.3 mL·day−1 of Mw intradermally or a matching placebo for three consecutive days. The primary outcome of the study was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The co-primary outcome was a change in SOFA score on days 7 and 14 compared to the baseline. The secondary outcomes were 28-day mortality, time to clinical recovery, time to RT-PCR negativity, adverse events, and othersResultsWe included 42 subjects (22 Mw, 20 placebo). On days 14 (OR, 30.4; 95% CI, 3.3–276.4) and 21 (OR, 14.9; 95% CI, 1.8–128.4), subjects in the Mw arm had a better clinical status distribution than placebo. There was no difference in the SOFA score change on days 7 and 14 between the two groups. We did not find any difference in the mortality, or other secondary outcomes. We observed no adverse events related to the use of Mw.ConclusionsThe use of Mw results in better clinical status distribution on days 14 and 21 compared to placebo in critically ill patients with COVID-19.

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Severe COVID‐19 and interleukin‐6 receptor antagonist tocilizumab: Some notes of concern

Abstract: See related reply

Cited by 5 publications

References 7 publications

The role of cytokines and their antagonists in the treatment of COVID‐19 patients

The role of cytokines and their antagonists in the treatment of COVID‐19 patients

Antibody-Based Immunotherapeutic Strategies for COVID-19

A randomised trial of Mycobacterium w in critically ill patients with COVID-19: ARMY-1

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