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In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy.
J Infect. 2021 04; 82(4):58-66.JI

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Clinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Clinical Division of Infectious Diseases, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy.Scientific Direction, National Institute for Infectious Disease "Lazzaro Spallanzani"-IRCCS, Rome, Italy.Rheumatology department, Azienda USL Toscana Centro, Hospital of Prato, Italy.Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy. Electronic address: delia.goletti@inmi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33639176

Citation

Petrone, Linda, et al. "In-vitro Evaluation of the Immunomodulatory Effects of Baricitinib: Implication for COVID-19 Therapy." The Journal of Infection, vol. 82, no. 4, 2021, pp. 58-66.
Petrone L, Petruccioli E, Alonzi T, et al. In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy. J Infect. 2021;82(4):58-66.
Petrone, L., Petruccioli, E., Alonzi, T., Vanini, V., Cuzzi, G., Najafi Fard, S., Castilletti, C., Palmieri, F., Gualano, G., Vittozzi, P., Nicastri, E., Lepore, L., Grifoni, A., Antinori, A., Vergori, A., Ippolito, G., Cantini, F., & Goletti, D. (2021). In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy. The Journal of Infection, 82(4), 58-66. https://doi.org/10.1016/j.jinf.2021.02.023
Petrone L, et al. In-vitro Evaluation of the Immunomodulatory Effects of Baricitinib: Implication for COVID-19 Therapy. J Infect. 2021;82(4):58-66. PubMed PMID: 33639176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In-vitro evaluation of the immunomodulatory effects of Baricitinib: Implication for COVID-19 therapy. AU - Petrone,Linda, AU - Petruccioli,Elisa, AU - Alonzi,Tonino, AU - Vanini,Valentina, AU - Cuzzi,Gilda, AU - Najafi Fard,Saeid, AU - Castilletti,Concetta, AU - Palmieri,Fabrizio, AU - Gualano,Gina, AU - Vittozzi,Pietro, AU - Nicastri,Emanuele, AU - Lepore,Luciana, AU - Grifoni,Alba, AU - Antinori,Andrea, AU - Vergori,Alessandra, AU - Ippolito,Giuseppe, AU - Cantini,Fabrizio, AU - Goletti,Delia, Y1 - 2021/02/25/ PY - 2020/12/12/received PY - 2021/02/09/revised PY - 2021/02/20/accepted PY - 2021/2/28/pubmed PY - 2021/4/10/medline PY - 2021/2/27/entrez KW - Baricitinib KW - COVID-19 KW - IGRA KW - SARS-CoV-2 KW - Specific immune-response SP - 58 EP - 66 JF - The Journal of infection JO - J Infect VL - 82 IS - 4 N2 - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1532-2742 UR - https://www.unboundmedicine.com/medline/citation/33639176/In_vitro_evaluation_of_the_immunomodulatory_effects_of_Baricitinib:_Implication_for_COVID_19_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-4453(21)00094-3 DB - PRIME DP - Unbound Medicine ER -