SARS-CoV-2 induced hypercytokinemia and inflammation are critically associated with COVID19 disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor, is currently being investigated in COVID-19 clinical trials.
In this paper published on Cell, are investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection.
Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type-I IFN antiviral responses and SARS-CoV-2-specific T-cell responses remained similar between the two groups.
Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology.
Importantly, baricitinib treated animals had a rapid and remarkably potent suppression of lung macrophages production of cytokines and chemokines responsible for inflammation and neutrophil recruitment.
These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection.
Emory University and Eli Lilly have developed a strategy for studying the safety and efficacy of an anti-inflammatory drug baricitinib as a potential treatment for patients hospitalized with COVID-19. The National Institute of Allergy and Infectious Diseases (NIAID) has agreed to evaluate a treatment regimen of the investigational antiviral remdesivir, plus the anti-inflammatory baricitinib, as part of the international Adaptive COVID-19 Treatment Trial (ACTT). Investigators currently anticipate enrolling more than 1,000 participants involving 100 US and international sites.
NIAID, part of the National Institutes of Health, said the randomized, controlled clinical trial to evaluate the safety and efficacy of the treatment regimen had begun and is now enrolling hospitalized patients with COVID-19 in the United States.
Baricitinib, typically used to treat rheumatoid arthritis, is a readily available oral treatment sold under the brand name Olumiant. Remdesivir is the antiviral recently described by Anthony Fauci, the director of NIAID, as the new standard of care in treating patients hospitalized with COVID-19 after preliminary data showed people with advanced coronavirus infection and lung involvement recovered faster than similar people who received placebo.
With the pandemic continuing across the globe, a group of Emory scientists, faculty and nurses have worked tirelessly to search for treatments that could help COVID-19 patients. Based on initial data, they believed the anti-inflammatory traits of the Lilly drug could prove useful in COVID-19 treatment.
As a result, Emory is taking part in the ongoing NIH-sponsored ACTT to evaluate the safety and efficacy of a treatment regimen of remdesivir, plus baricitinib, in patients hospitalized with COVID-19. All participants in this trial, called ACTT 2, will receive remdesivir or remdesivir with baricitinib.
“There is an urgent need for new strategies to help hospitalized COVID-19 patients, many of whom will progress to respiratory failure,” says Vincent C. Marconi, MD, professor of medicine and global health in Emory University School of Medicine and Emory’s Rollins School of Public Health. “This NIAID study presents an important opportunity to test whether baricitinib can help these patients who are desperate for effective therapies.”
Raymond F. Schinazi, PhD, DSc, the Frances Winship Walters Professor of Pediatrics and one of the lead virologists in the study, says he “was pleased Emory and other centers were chosen to work with Lilly and NIH in determining the value in treating SARS-CoV2 infections with baricitinib.”
“The inflammatory response in the lung,” he says, “is causing mayhem in infected people and the hope is for baracitinib to wipe out this powerful cytokine storm, which sometimes becomes a hurricane.”
“We are pleased to have produced at Emory and the Atlanta VA Medical Center important data to support these studies in humans in a controlled and scientifically robust way,” Schinazi says. “We are highly motivated to use our expertise in infectious diseases and clinical medicine to find effective cures for COVID-19 to save as many lives as possible as rapidly as possible.”
For the past eight years, Schinazi, Marconi and Christina Gavegnano, PhD, assistant professor of pediatrics at Emory, have been exploring the role of baricitinib and other Jak inhibitors as a treatment for patients with HIV based on in-vitro studies by Gavegnano and Schinazi.
COVID-19 starts as an upper respiratory tract infection, often indistinguishable from other more common respiratory tract infections. First detected in Wuhan, China, the novel coronavirus has spread rapidly around the globe.
The NIAID ACCT trial is also supported by multiple networks including NIAID’s Infectious Diseases Research Consortium composed of the nations’ Vaccine and Treatment Evaluation Units Treatment and Evaluation Units (VTEUs).
The ACTT trial is found on ClinicalTrials.gov and search identifier NCT04280705.
Leave a Reply