Baricitinib restrains the immune dysregulation in COVID-19 patients
clinical drug discovery/repurposing immunology/immunity inflammation therapeutics
Authors:Bronte et al.,
Journal/ Pre-Print: medrxiv
Tags: Clinical, Drug repurpose, Immunology/Immunity, Inflammation, Therapeutics.
Baricitinib treated patients had significantly lower mortality (5%) than clinically and demographically matched patients not treated with Baricitinib (45%).
Baricitinib treatment restores normal lymphocyte counts (e.g. of B cells, CD4+ T cells and CD8+ T cells), increased IgG levels specific for the SARS-CoV-2 spike protein, and decreased proinflammatory cytokine (e.g. IL-6, IL-1 β and TNF-α) levels in the blood compared to control patients.
Baricitinib treatment decreased the in vitro immune suppressive abilities of monocytes during the recovery phase.
This study reports on 20 severe COVID19 patients who were treated with Baricitinib, an FDA approved inhibitor of the Janus kinases (JAK1 and JAK2), which drive the response to proinflammatory cytokines (e.g. type I IFNs and IL-6). The authors surmised this could improve the disease course of COVID-19 patients by attenuating the cytokine storm thought to drive pathology of the disease. Indeed, the authors find (while adjusting for confounding factors) that Baricitinib significantly reduced mortality in treated (n=20, 5% mortality) patients compared to untreated patients (n=56, 45% mortality). However, Baricitinib treatment did not correlate with reduced disease duration or fever resolution, but Baricitinib treated patients had improved lung function as measured by oxygen uptake and reduced levels of C reactive protein, a prognostic marker of poor disease outcome.
Impact for SARS-CoV2/COVID19 research efforts
Treat of SARS-CoV2/COVID19 positive individuals
Using Baricitinib presents a promising strategy to treat patients with ongoing SARS-CoV2 infections in the absence of functional antiviral treatments or vaccines.
Clinical Cohort study (e.g. drug trials)
Patient Case study
Strengths and limitations of the paper
Novelty: Phase III clinical trials for treatment of SARS-CoV2 patients with Baricitinib are currently being conducted. Only one other paper discusses safety of Baricitinib treatment in mild cases of SARS-CoV2 in a small cohort (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177073/#!po=43.7500).
This study is novel in that it addresses the clinical outcome and efficacy of Baricitinib in COVID-19 patients. This study shows the impact of short-term treatment with Baricitinib in normalising the immune landscape in COVID-19 patients. Importantly, Baricitinib can be orally given to patients outside hospitals, which may have a significant impact in limiting the number of hospitalised COVID-19 patients during the pandemic, with potentially significant effects on the global health care system.
Standing in the field:The findings are in line with current literature and similar reports.
Viral model used:Patients with qPCR-positive SARS-CoV2 in intensive care.
Translatability:Yes, there is the potential to use the already FDA approved drug Baricitinib to treat SARS-CoV2 patients.
The Baricitinib-treated cohort appear to have higher initial IgG antibody titres specific to the spike protein. This could potentially explain why the treated group fared better over time.
This study was not double-blinded.
One of the main and interesting data, the ability of Baricitinib to modify the immune suppressive features of myeloid cells, was showed in only one patient.