In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy

•Baricitinib has been suggested as a promising therapy for COVID-19.•Baricitinib modulates in vitro SARS-CoV-2-specific-response in a whole blood platform.•Baricitinib decreases viral-specific-response mainly in mild/moderate COVID-19. Baricitinib seems a promising therapy for COVID-19. To fully-inv...

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Published in:The Journal of infection Vol. 82; no. 4; pp. 58 - 66
Main Authors: Petrone, Linda, Petruccioli, Elisa, Alonzi, Tonino, Vanini, Valentina, Cuzzi, Gilda, Najafi Fard, Saeid, Castilletti, Concetta, Palmieri, Fabrizio, Gualano, Gina, Vittozzi, Pietro, Nicastri, Emanuele, Lepore, Luciana, Grifoni, Alba, Antinori, Andrea, Vergori, Alessandra, Ippolito, Giuseppe, Cantini, Fabrizio, Goletti, Delia
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.04.2021
The Authors. Published by Elsevier Ltd on behalf of The British Infection Association
Subjects:
Azetidines
Baricitinib
COVID-19
COVID-19 Drug Treatment
Cytokines
Humans
IGRA
Purines
Pyrazoles
SARS-CoV-2
Specific immune-response
Sulfonamides
COVID-19
SARS-CoV-2
Specific immune-response
Baricitinib
IGRA
ISSN:0163-4453, 1532-2742, 1532-2742
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Summary:•Baricitinib has been suggested as a promising therapy for COVID-19.•Baricitinib modulates in vitro SARS-CoV-2-specific-response in a whole blood platform.•Baricitinib decreases viral-specific-response mainly in mild/moderate COVID-19. Baricitinib seems a promising therapy for COVID-19. To fully-investigate its effects, we in-vitro evaluated the impact of baricitinib on the SARS-CoV-2-specific-response using the whole-blood platform. We evaluated baricitinib effect on the IFN-γ-release and on a panel of soluble factors by multiplex-technology after stimulating whole-blood from 39 COVID-19 patients with SARS-CoV-2 antigens. Staphylococcal Enterotoxin B (SEB) antigen was used as a positive control. In-vitro exogenous addition of baricitinib significantly decreased IFN-γ response to spike- (median: 0.21, IQR: 0.01–1; spike+baricitinib 1000 nM median: 0.05, IQR: 0–0.18; p < 0.0001) and to the remainder-antigens (median: 0.08 IQR: 0–0.55; remainder-antigens+baricitinib 1000 nM median: 0.03, IQR: 0–0.14; p = 0.0013). Moreover, baricitinib significantly decreased SEB-induced response (median: 12.52, IQR: 9.7–15.2; SEB+baricitinib 1000 nM median: 8, IQR: 1.44–12.16; p < 0.0001). Baricitinib did modulate other soluble factors besides IFN-γ, significantly decreasing the spike-specific-response mediated by IL-17, IL-1β, IL-6, TNF-α, IL-4, IL-13, IL-1ra, IL-10, GM-CSF, FGF, IP-10, MCP-1, MIP-1β (p ≤ 0.0156). The baricitinib-decreased SARS-CoV-2-specific-response was observed mainly in mild/moderate COVID-19 and in those with lymphocyte count ≥1 × 103/µl. Exogenous addition of baricitinib decreases the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. These results are the first to show the effects of this therapy on the immune-specific viral response. [Display omitted]
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ISSN:0163-4453
1532-2742
1532-2742
DOI:10.1016/j.jinf.2021.02.023