Baricitinib: the first immunomodulatory treatment to reduce COVID-19 mortality in a placebo-controlled trial

Antibacterial, antifungal, antiviral, and antiparasitic treatments developed in the past century have improved survival outcomes, even in high-mortality conditions such as sepsis, a condition that is mostly caused by bacteria but can also be due to other infections. In the 21st century, of all therapies that have improved the outcomes of patients with sepsis, the appropriate and early administration of antibiotics has been shown to be the most effective therapy to save lives.1 However, despite highly effective antibiotics that can kill microorganisms causing sepsis, and cultures showing eradication of these organisms, overall mortality from the condition remains high. In part, this high mortality might be explained by dysregulated immune responses arising from redundant pathways in the human immune system, which have developed—along with the array of defensive mechanisms involving the innate and adaptive responses, inflammation, and coagulation—as a result of the selective pressure of thousands of years of exposure to infections, zoonoses, and resulting epidemics and pandemics. This dysregulated immune response can be as harmful as, or more harmful than, the pathogens themselves.2 Accordingly, two original studies showed significant reduction in mortality due to sepsis among solid organ transplant recipients compared with patients without transplants.3, 4 This finding suggests that immunosuppressive drugs, required lifelong to avoid transplant graft rejection, might have been protective by decreasing dysfunctional responses to sepsis. These lessons learned from bacterial sepsis are highly relevant in the context of COVID-19...