BACKGROUND Patients 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.METHODS We 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.RESULTS We 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.CONCLUSION These 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 REGISTRATION ClinicalTrials.gov NCT04438629.FUNDING This work was supported by the Fondazione Cariverona (ENACT Project) and the Fondazione TIM.
Vincenzo Bronte, Stefano Ugel, Elisa Tinazzi, Antonio Vella, Francesco De Sanctis, Stefania Canè, Veronica Batani, Rosalinda Trovato, Alessandra Fiore, Varvara Petrova, Francesca Hofer, Roza Maria Barouni, Chiara Musiu, Simone Caligola, Laura Pinton, Lorena Torroni, Enrico Polati, Katia Donadello, Simonetta Friso, Francesca Pizzolo, Manuela Iezzi, Federica Facciotti, Pier Giuseppe Pelicci, Daniela Righetti, Paolo Bazzoni, Mariaelisa Rampudda, Andrea Comel, Walter Mosaner, Claudio Lunardi, Oliviero Olivieri