Baricitinib restrains the immune dysregulation in patients with severe COVID-19
| Autor: | Veronica Batani, Manuela Iezzi, Daniela Righetti, Stefano Ugel, Simone Caligola, Enrico Polati, Pier Giuseppe Pelicci, Walter Mosaner, Claudio Lunardi, Katia Donadello, Francesco De Sanctis, Alessandra Fiore, Varvara Petrova, Simonetta Friso, Federica Facciotti, Lorena Torroni, Andrea Claudio Comel, Paolo Bazzoni, Laura Pinton, Francesca Pizzolo, Mariaelisa Rampudda, Francesca Hofer, Elisa Tinazzi, Rosalinda Trovato, Vincenzo Bronte, Antonio Vella, Stefania Canè, Oliviero Olivieri, Chiara Musiu, Roza Maria Barouni |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Myeloid T-Lymphocytes medicine.medical_treatment medicine.disease_cause Severity of Illness Index 03 medical and health sciences 0302 clinical medicine Immune system Fraction of inspired oxygen Oxygen therapy medicine Humans Longitudinal Studies B cell Aged Aged 80 and over B-Lymphocytes Sulfonamides biology SARS-CoV-2 business.industry COVID-19 Off-Label Use General Medicine Middle Aged Immune dysregulation COVID-19 Drug Treatment 030104 developmental biology medicine.anatomical_structure Cytokine Purines 030220 oncology & carcinogenesis Immunology Commentary biology.protein Azetidines Cytokines Pyrazoles Female Antibody business |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci141772 |
| Popis: | BACKGROUNDPatients with coronavirus disease 2019 (COVID-19) develop pneumonia generally associated with lymphopenia and a severe inflammatory response due to uncontrolled cytokine release. These mediators are transcriptionally regulated by the JAK/STAT signaling pathways, which can be disabled by small molecules.METHODSWe treated a group of patients (n = 20) with baricitinib according to an off-label use of the drug. The study was designed as an observational, longitudinal trial and approved by the local ethics committee. The patients were treated with 4 mg baricitinib twice daily for 2 days, followed by 4 mg per day for the remaining 7 days. Changes in the immune phenotype and expression of phosphorylated STAT3 (p-STAT3) in blood cells were evaluated and correlated with serum-derived cytokine levels and antibodies against severe acute respiratory syndrome-coronavirus 2 (anti-SARS-CoV-2). In a single treated patient, we also evaluated the alteration of myeloid cell functional activity.RESULTSWe provide evidence that patients treated with baricitinib had a marked reduction in serum levels of IL-6, IL-1β, and TNF-α, a rapid recovery of circulating T and B cell frequencies, and increased antibody production against the SARS-CoV-2 spike protein, all of which were clinically associated with a reduction in the need for oxygen therapy and a progressive increase in the P/F (PaO2, oxygen partial pressure/FiO2, fraction of inspired oxygen) ratio.CONCLUSIONThese data suggest that baricitinib prevented the progression to a severe, extreme form of the viral disease by modulating the patients' immune landscape and that these changes were associated with a safer, more favorable clinical outcome for patients with COVID-19 pneumonia.TRIAL REGISTRATIONClinicalTrials.gov NCT04438629.FUNDINGThis work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM. |
| Databáze: | OpenAIRE |
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