2022
DOI: 10.3389/fimmu.2022.795315
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Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling

Abstract: Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study… Show more

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Cited by 51 publications
(51 citation statements)
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References 128 publications
(305 reference statements)
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“…The authors suggested that the level of CD3+CD4+ T cells could have a predictive value for the early detection of severe COVID-19 forms and the selection of patients requiring rapid aggressive treatment with corticosteroids or IL-6 inhibitors. However, IL-6 blockade may not be effective in some severe COVID-19 [ 83 ], and largely depended on many factors including baseline IL-6 levels, PaO 2 /FIO 2 , requirement of HFO or NIV, levels of CRP, ferritin, D-dimer, and LDH [ 84 , 85 ].…”
Section: Cd4 T Cells and Their Subsets In Covid-19mentioning
confidence: 99%
“…The authors suggested that the level of CD3+CD4+ T cells could have a predictive value for the early detection of severe COVID-19 forms and the selection of patients requiring rapid aggressive treatment with corticosteroids or IL-6 inhibitors. However, IL-6 blockade may not be effective in some severe COVID-19 [ 83 ], and largely depended on many factors including baseline IL-6 levels, PaO 2 /FIO 2 , requirement of HFO or NIV, levels of CRP, ferritin, D-dimer, and LDH [ 84 , 85 ].…”
Section: Cd4 T Cells and Their Subsets In Covid-19mentioning
confidence: 99%
“…Critical and severe COVID-19 forms, constituting 2–5% and 15% of cases, respectively, are assumed to occur from SARS-CoV-2-induced autoinflammatory syndrome, both at systemic and pulmonary levels, in which a dysregulated immune response, due to overflowing cytokine production and release, leads to widespread tissue and vascular damages [ 30 ]. Viral infections and autoimmune pathologies are known to be correlated to an abnormal immune response known as a “cytokine storm”, characterized by an excessive release of pro-inflammatory cytokines [ 31 , 32 ].…”
Section: Cytokine Storm and Rationale For Il-6 Inhibitor Administrati...mentioning
confidence: 99%
“…In conclusion, therapeutic blockade of IL-6 pathways should not be performed in critically ill patients, in whom IL-6 cis-signaling is predominant with favorable homeostatic roles, nor in the early (viral) phase of SARS-CoV-2 infection, in which IL-6 signaling may be useful to block viral replication and dissemination [ 30 ]. The proven benefits of anti-IL-6 treatment in COVID-19 patients could be achieved by disrupting only pro-inflammatory IL-6 trans-presentation and trans-signaling, prevalent and pathogenic in severe disease, by acting no later than the second week of symptom onset (or within seven days of hospitalization) [ 30 ].…”
Section: Cytokine Storm and Rationale For Il-6 Inhibitor Administrati...mentioning
confidence: 99%
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