Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know So Far?

Plocque, Alexia; Mitri, Christie; Lefèvre, Charlène; Tabary, Olivier; Touqui, Lhousseine; Philippart, François

doi:10.1007/s40265-022-01803-2

Cited by 7 publications

(6 citation statements)

References 178 publications

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“…The narrative review reported by Plocque and colleagues [ 1 ] elegantly discussed if interleukin-6 (IL-6) receptor inhibitors should be used in the management of coronavirus disease 2019 (COVID-19). Undeniably, as discussed by the authors, the interruption of the IL-6 pathway by administering IL-6 receptor inhibitors, especially tocilizumab, could reduce the risk of mortality in patients with COVID-19 who are high-flow oxygen-dependent as well as patients with COVID-19 who have recently been admitted to the intensive care unit.…”

mentioning

confidence: 99%

“…Nevertheless, despite their mortality benefits, the potential risks associated with IL-6 receptor inhibitors during the management of COVID-19 are still unclear. In their review, the authors have discussed the potential increased risk of nosocomial infections [ 1 ]. We intend to complement their discussion by raising another perspective that should be considered while using IL-6 receptor inhibitors in patients with COVID-19.…”

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confidence: 99%

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Comment on: ‘Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know?’

Kow

Ramachandram

Hasan

2023

Drugs

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confidence: 99%

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confidence: 99%

Comment on: ‘Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know?’

Kow

Ramachandram

Hasan

2023

Drugs

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“…This underlined the assumption that COVID-19 was comparable to sepsis and led to the idea that these biomarker levels were the cause for organ failure and, thus, needed to be suppressed [16][17][18][19][20][21]. Therefore, several clinical trials started using anti-inflammatory therapies to try to reduce the cytokine plasma levels [22][23][24] (Table 2). These clinical trials have not been successful so far and, in some cases, have even worsened patient outcomes [25,26].…”

Section: Covid-19-induced Sepsis Immunotherapies and Antiviral Treatm...mentioning

confidence: 99%

A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis

Brandenburg,

Ferrer-Espada,

Martinez-de-Tejada

et al. 2023

IJMS

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Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels.

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“…High IL-6 levels exert pleiotropic effects on the immune system through cis-signaling, resulting in cytokine release syndrome (CRS) [ 24 ]. IL-6 inhibitor has been shown to be effective in patients with severe COVID-19 and have become one of the standard treatments against COVID-19, but the best beneficiary group needs to be evaluated [ 25 ].…”

Section: Covid-19 Immunologymentioning

confidence: 99%

SARS-CoV-2 infection and COVID-19 vaccination in cancer patients undergoing immune checkpoint inhibitors

Yang

2023

Cell Death Dis

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Cancer patients are susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Different antitumor treatments have attracted wide attention in the context of coronavirus disease 2019 (COVID-19), especially immune checkpoint inhibitors (ICIs) that have revolutionized oncology changes. It may also have protective and therapeutic roles in viral infections. In this article, we collected 26 cases of SARS-CoV-2 infection during ICIs therapy and 13 related to COVID-19 vaccination from Pubmed, EMBASE, and Wed of Science. Of these 26 cases, 19 (73.1%) presented mild cases and 7 (26.9%) were severe cases. Melanoma (47.4%) was a common cancer type in mild cases and lung cancer (71.4%) in severe cases (P = 0.016). The results showed that their clinical outcomes varied widely. Although there are similarities between the immune checkpoint pathway and COVID-19 immunogenicity, ICIs therapy overactivated T cells, which often leads to immune-related adverse events. In fact, the COVID-19 vaccine has been shown to be safe and effective in patients treated with ICIs. In this review, we report the vital clinical observations of SARS-CoV-2 infection or vaccination in cancer patients treated with ICIs and explore the potential interaction between them.

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Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know So Far?

Cited by 7 publications

References 178 publications

Comment on: ‘Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know?’

Comment on: ‘Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know?’

A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis

SARS-CoV-2 infection and COVID-19 vaccination in cancer patients undergoing immune checkpoint inhibitors

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