Rethinking interleukin-6 blockade for treatment of COVID-19

Scherger, Sias; Henao‐Martínez, Andrés F.; Franco‐Paredes, Carlos; Shapiro, Leland

doi:10.1016/j.mehy.2020.110053

Cited by 35 publications

(25 citation statements)

References 38 publications

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“…Nevertheless, IL-6-blocking substances must not be seen as the final key treatments to combat COVID-19, as IL-6 is not solely responsible for the cytokine storm in COVID-19 because it still remains unclear whether elevated IL-6 in viral infections, and SARS-CoV-2 in particular, represents a therapeutic target or part of a functioning adaptive immune response. Indeed, studies have shown that intravenous administration of monoclonal IL-6 in healthy volunteers, at levels significantly exceeding the concentrations found in COVID-19, did not result in pulmonary adverse events, which further questions the importance of IL-6 in COVID-19 [ 109 , 110 ]. Moreover, patients with severe COVID-19 who have been administered anti–IL-6 treatments have reported having higher numbers of secondary infections [ 111 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

Pum

Ennemoser

Adage³

et al. 2021

Biomolecules

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The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.

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Section: Discussionmentioning

confidence: 99%

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

Pum

Ennemoser

Adage³

et al. 2021

Biomolecules

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“…Despite the undoubted efficacy of IL-6 inhibitors in patients with severe COVID-19, the role of these drugs and IL-6 in the pathogenesis of CSS should be further investigated [ [111] , [112] , [113] ]. In patients with severe COVID-19, the average concentration of IL-6 in the blood serum is significantly lower (in the range from 7 to 627 mg/ml, on average 132.32 ± 278.54 pkg/ml) [ 26 , [114] , [115] , [116] , [117] ] than in patients with ARDS caused by other viral infections (578-1618 pg/ml) [ [118] , [119] , [120] ].…”

Section: Future Perspectivesmentioning

confidence: 99%

The role of Interleukin 6 inhibitors in therapy of severe COVID-19

Насонов

Samsonov

2020

Biomedicine & Pharmacotherapy

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Graphical abstract The role of interleukin 6 inhibitors in therapy of severe COVID-19 Nassonov E, Samsonov M. RM, Resident macrophages; INF, interferons; NK, natural killers; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor, TNFα, tumor necrosis factor alpha; IP-10, interferon (IFN)γ-induced protein 10; MIP1α, macrophage inflammatory protein; CCL2, CCL7, CXCL9, CXCL10, chemokines.

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“…Although some studies found considerable clinical improvements resulting from treatment with IL-6 blockers (236-239), others do not report any significant difference between the clinical features of groups treated with anti-IL6/ IL-6R mAbs and their respective controls (without anti-IL-6/IL-6R) (240)(241)(242)(243). These controversial results can be explained by the pleiotropic function of IL-6, which also play an important anti-inflammatory role, questioning the use of IL-6 blockade to suppress inflammation-induced tissue damage (244). Additionally, severe side effects have been associated with the use of IL-6 blockers, including enhanced hepatic enzymes, thrombocytopenia, severe bacterial and fungal infections, and sepsis (241,245).…”

Section: Antibody-based Therapymentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.

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Rethinking interleukin-6 blockade for treatment of COVID-19

Cited by 35 publications

References 38 publications

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

The role of Interleukin 6 inhibitors in therapy of severe COVID-19

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

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