In-vitro evaluation of the immunomodulatory effects of Baricitinib : Implication for COVID-19 therapy
Copyright © 2021. Published by Elsevier Ltd..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:82 |
|---|---|
| Enthalten in: |
The Journal of infection - 82(2021), 4 vom: 01. Apr., Seite 58-66 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Petrone, Linda [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Azetidines |
|---|
| Anmerkungen: |
Date Completed 09.04.2021 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jinf.2021.02.023 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM321970802 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM321970802 | ||
| 003 | DE-627 | ||
| 005 | 20231225181033.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jinf.2021.02.023 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1073.xml |
| 035 | |a (DE-627)NLM321970802 | ||
| 035 | |a (NLM)33639176 | ||
| 035 | |a (PII)S0163-4453(21)00094-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Petrone, Linda |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In-vitro evaluation of the immunomodulatory effects of Baricitinib |b Implication for COVID-19 therapy |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.04.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021. Published by Elsevier Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Baricitinib | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a IGRA | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Specific immune-response | |
| 650 | 7 | |a Azetidines |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Purines |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a baricitinib |2 NLM | |
| 650 | 7 | |a ISP4442I3Y |2 NLM | |
| 700 | 1 | |a Petruccioli, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Alonzi, Tonino |e verfasserin |4 aut | |
| 700 | 1 | |a Vanini, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Cuzzi, Gilda |e verfasserin |4 aut | |
| 700 | 1 | |a Najafi Fard, Saeid |e verfasserin |4 aut | |
| 700 | 1 | |a Castilletti, Concetta |e verfasserin |4 aut | |
| 700 | 1 | |a Palmieri, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Gualano, Gina |e verfasserin |4 aut | |
| 700 | 1 | |a Vittozzi, Pietro |e verfasserin |4 aut | |
| 700 | 1 | |a Nicastri, Emanuele |e verfasserin |4 aut | |
| 700 | 1 | |a Lepore, Luciana |e verfasserin |4 aut | |
| 700 | 1 | |a Grifoni, Alba |e verfasserin |4 aut | |
| 700 | 1 | |a Antinori, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Vergori, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Ippolito, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Cantini, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Goletti, Delia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of infection |d 1982 |g 82(2021), 4 vom: 01. Apr., Seite 58-66 |w (DE-627)NLM012791822 |x 1532-2742 |7 nnns |
| 773 | 1 | 8 | |g volume:82 |g year:2021 |g number:4 |g day:01 |g month:04 |g pages:58-66 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jinf.2021.02.023 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 82 |j 2021 |e 4 |b 01 |c 04 |h 58-66 | ||