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.

The role of phytochemicals as potential prodrugs or therapeutic substances against tumors has come in the spotlight in the very recent years, thanks to the huge mass of encouraging and promising results of the in vitro activity of many phenolic compounds from plant raw extracts against many cancer cell lines. Little but important evidence can be retrieved from the clinical and nutritional scientific literature, where flavonoids are investigated as major pro-apoptotic and anti-metastatic compounds. However, the actual role of these compounds in cancer is still far to be fully elucidated. Many of these phytochemicals act in a pleiotropic and poorly specific manner, but, more importantly, they are able to tune the reactive oxygen species (ROS) signaling to activate a survival or a pro-autophagic and pro-apoptosis mechanism, depending on the oxidative stress-responsive endowment of the targeted cell. This review will try to focus on this issue.

Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions.

Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.