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

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 × 10 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.

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Copyright © 2021. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr Emanuele Nicastri reported consultancies from Gilead under $10,000 and outside the present work. Dr Alba Grifoni is listed as inventor on a provisional patent application on the diagnostic and therapeutic use of the MPs and peptides thereof filed on February 12, 2020. Dr Andrea Antinori reported consultancies, speaking fees and honoraria from Gilead Sciences, Janssen Cilag, Merk, VIIVHealthcare, Theratechnologies, all under $10,000 and outside the present work. Dr Alessandra Vergori received institutional grants from Gilead, travel grants and speaker's fees from Janssen and speaker's fee from MSD, all under $10,000 and outside the present work. Dr Delia Goletti reported consultancies from Quidel and Biomeriuex and speaking fees from Diasorin and Janssen, all under $10,000 and outside the present work.All the other authors have declared that no conflict of interest and/or financial disclosures exists.