An inter-correlated cytokine network identified at the center of cytokine storm predicted COVID-19 prognosis

Liu, Yili; Chen, Daihong; Hou, Junjie; Li, Haicong; Cao, Dan; Guo, Mingquan; Ling, Yun; Gao, Menglu; Zhou, Yi; Wan, Yanmin; Zhu, Zhaoqin

doi:10.1016/j.cyto.2020.155365

Cited by 40 publications

(46 citation statements)

References 20 publications

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“…Furthermore, COVID-19 patients have a larger number of activated monocytes that infiltrate the lungs and lead to damage [ 45 ]. IL-6 is secreted by monocytes and macrophages and might play a central role in SARS-CoV-2-induced cytokine storms [ 46 ]; this cytokine inhibits the Th1 response [ 47 ], which is observed in severe COVID-19 patients [ 48 ], and it attenuates cytotoxic CD8+ T cell activity [ 49 ] and promotes differentiation and Th17-dependent virus persistence and immunopathology ( Figure 5 ) [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

et al. 2021

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The pandemic of the new coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to the deaths of more than 1.5 million people worldwide. SARS-CoV-2 causes COVID-19, which exhibits wide variation in the course of disease in different people, ranging from asymptomatic and mild courses to very severe courses that can result in respiratory failure and death. Despite the rapid progression of knowledge, we still do not know how individual cells of the immune system interact with the virus or its components, or how immune homeostasis becomes disrupted, leading to the rapid deterioration of a patient’s condition. In the present work, we show that SARS-CoV-2 proteins induce the expression and secretion of IL-6 by human monocytes and macrophages, the first line cells of antiviral immune responses. IL-6 may play a negative role in the course of COVID-19 by inhibiting Th1-dependent immunity and stimulating Th17 lymphocytes, thus leading to an increased probability of a cytokine storm.

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Section: Discussionmentioning

confidence: 99%

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

et al. 2021

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“…The last phase is characterised by a further increase of IL-5 on days 16–20 and a relative slowdown of blood eosinophil count on days 16–20 ( Lucas et al, 2020 ). Finally, deceased patients had higher levels of IL-5 than patients with moderate or severe disease ( Liu et al, 2020 ).…”

Section: Th2 Immune Response In Severe Patientsmentioning

confidence: 99%

“…Nevertheless, eosinophils enrollment during the second phase may contribute to harm target tissues and progress the pathology. In the last phase of a severe course, the immune system undertakes a pathologic pathway characterized by a broad and uncontrolled cytokines storm, with a new pathological increase of IL-5 ( Lucas et al, 2020 ; Bouadma et al, 2020 ; Liu et al, 2020 ).…”

Section: Th2 Immune Response In Severe Patientsmentioning

confidence: 99%

Anti-IL5 Drugs in COVID-19 Patients: Role of Eosinophils in SARS-CoV-2-Induced Immunopathology

Pala

Pistis

2021

Front. Pharmacol.

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SARS-CoV-2 infection stimulates a complex activation of the immune system. Eosinophils belong to the host’s defense equipment against respiratory viruses. In the first phase of the infection, eosinophils contribution is probably appropriate and beneficial, as they facilitate the suppression of the viral replication. However, in severe COVID-19 patients, during the second and third phases of the disease, eosinophils may participate in a maladaptive immune response and directly contribute to immunopathology. In fact, in severe patients, the immune response is prevalently T helper 1 type, but T helper 2 is also present. Eosinophils’ expansion and activation are stimulated by Type 2 cytokines, especially IL-5. Moreover, bronchial asthma, in which eosinophils play a central role, seems not to be a major risk factor for severe COVID-19. Among possible explanations, asthmatic patients are often treated with corticosteroids, which have been demonstrated to reduce the progression to critical COVID-19 in hospitalized patients. In addition to steroids, severe asthmatic patients are currently treated with biological drugs that target Type 2 immune response. Because IL-5 is necessary for the growth, survival, and activation of eosinophils, IL-5 inhibitors, such as mepolizumab, decrease the peripheral blood count of eosinophils, but do not influence eosinophils activation in the airway. In severe COVID-19 patients, the blockade of eosinophils’ activation might contrast harmful immunity.

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“… 74 In severe COVID-19, IL-6 has been shown to be central among a network of 12 cytokines that are elevated in cases with poor prognoses. 75 …”

Section: Clinical Course and Inflammatory Pathology Of Sars-cov-2 Infmentioning

confidence: 99%

“…Based on the central role for IL-6 in the inflammatory pathology of COVID-19 75 and a consistent association between elevated levels of the cytokine and severe disease outcomes, 10 22 23 25 112 113 cytokine-modulatory therapies were proposed as a strategy to break the cycle of hyperinflammation. Reports from China 28 114 and Italy, 96 115 regions that were among the hardest-hit during the early months of 2020, seemed to demonstrate miraculous recoveries with anti-IL-6 therapies.…”

Section: Rationale For Targeting Il-6mentioning

confidence: 99%

IL-6 modulation for COVID-19: the right patients at the right time?

Ascierto

Wei

2021

J Immunother Cancer

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The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage—as defined clinically by C reactive protein levels higher than 75 mg/L.

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An inter-correlated cytokine network identified at the center of cytokine storm predicted COVID-19 prognosis

Cited by 40 publications

References 20 publications

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

Nucleocapsid and Spike Proteins of the Coronavirus SARS-CoV-2 Induce IL6 in Monocytes and Macrophages—Potential Implications for Cytokine Storm Syndrome

Anti-IL5 Drugs in COVID-19 Patients: Role of Eosinophils in SARS-CoV-2-Induced Immunopathology

IL-6 modulation for COVID-19: the right patients at the right time?

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