Episode 108 Part 2
Immunomodulatory treatments
Guido Vanham
5-6 Feb 2021
Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation
Giulio Cavalli Front Pharmacol Dec 2020
6/02/2021 2
Main pathways and treatment targets in SARS-CoV-2–induced immune response In the early stage of SARS-CoV-2 infection, infected cells and resident macrophages release signaling molecules that recruit host immune cells into the alveolar space. These cells, mainly neutrophils, T-lymphocytes and monocytes, produce and release high levels of inflammatory cytokines, leading to an uncontrolled inflammatory response (GM-CSF, granulocyte-monocyte colony-stimulating factor; IL, interleukin; JAK, Janus kinase; TNF, tumor necrosis factor).
Immunopathogenesis and treatment of cytokine storm in COVID-19
Seok Kim Theranostics Jan 2021
6/02/2021 3
Pathophysiology and treatment of cytokine storm in COVID-19. Type-1 IFNs play a major role in inhibiting the early stage of COVID-19 infection. Dendritic cells and mononuclear macrophages that recognize viral antigens induce an acute phase response through pro-inflammatory cytokines such as IL-6, IL-1, and TNF-α.
Among them, IL-6 stimulates T-cells to activate adaptive immunity. Activated T cells also stimulate macrophage and NK cells through IFN-γ to promote
virus removal. Failure of the initial immune response by type-1 IFNs increases excessively the activity of immune system leading to cytokine storm. Aerosolized type-1 IFNs promotes an initial immune response to remove virus, corticosteroids and novel cytokine blockades inhibits immune responses to prevent cytokine storm.
ACE2: angiotensin converting enzyme-2; COVID-19: coronavirus disease 2019; IFN: interferon; IL: interleukin; JAK/STAT; Janus kinase-signal transducer and activator of transcription; NK: natural killer; RLR: retinoic acid-inducible gene-1-like receptor; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TCR: T cell receptor; TCZ: tocilizumab; TLR: toll-like receptor; TNF-α: tumor necrosis factor-alpha.
The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review
Kaye AG PeerJ 8:e10322 Nov 2020
The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review
Kaye AG PeerJ 8:e10322 Nov 2020
The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review
Kaye AG PeerJ 8:e10322 Nov 2020
The efficacy of IL-6 inhibitor Tocilizumab in reducing severe COVID-19 mortality: a systematic review
Kaye AG PeerJ 8:e10322 Nov 2020
Efficacy and safety of tocilizumab in COVID-19 patients
Tleyjeh Clin Microbiol Infect Nov 2020
6/02/2021 8
A. 28-30 days mortality risk
Efficacy and safety of tocilizumab in COVID-19 patients
Tleyjeh Clin Microbiol Infect Nov 2020
6/02/2021 9
Risk for infection
Efficacy and safety of tocilizumab in COVID-19 patients
Tleyjeh Clin Microbiol Infect Nov 2020
6/02/2021 10
Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation
Della Torre Ann Rheum Dis 2020;79
Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19
Ruiz-Antoran Infect Dis Ther Dec 2020
Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19
Ruiz-Antoran Infect Dis Ther Dec 2020
6/02/2021 14
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
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Preliminary report
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
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Preliminary report
REMAP-CAP medRxiv 7 Jan 2021
6/02/2021 16
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
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Preliminary report
6/02/2021 17
Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical COVID-19
6/02/2021 18
Efficacy of canakinumab in mild or severe COVID‐19 pneumonia
6/02/2021 19
Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study
Generali IJID Dec 2020
Table 2: Changes in PaO2/FiO2 ratio and lung damage evaluated by chest CT (%) in cohort 1 (I) on Canakinimab and cohort 2 (II) on standard care during the same time period before treatment with canakinumab and at 7-10 days after the second administration;
Correlation between PaO2:FiO2 ratio and lung damage at chest CT (III).
6/02/2021 20
Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study
Generali IJID Dec 2020
6/02/2021 21
Canakinumab as treatment for COVID-19-related pneumonia: a prospective case-control study
Generali IJID Dec 2020
6/02/2021 22
Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe
COVID-19 pneumonia and moderate hyperinflammation.
6/02/2021 23
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
A.C. Kalil NEJM 5 Jan 2021
706 patients with moderate disease (ordinal score of 4 or 5 [not receiving ventilation])
6/02/2021 24
Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia:
6/02/2021 25
