Research Digest is a periodic installment that recognizes the world-class clinical research performed right here at UNMC ID. Today, we review three articles covering clinical trials that evaluate new drugs for the treatment of COVID-19, using three different approaches. As always, check out the linked full articles for more details.
In the first article, published in the journal Infection and co-authored by the late Dr. Diana Florescu, the authors examine the data from a phase 3 randomized and placebo-controlled trial of the antiviral medication molnupiravir specifically in immunocompromised patients. This medication works by inhibiting the ability of the virus to replicate and infect other cells. The study found a large reduction in hospitalization, death, and adverse events in immunocompromized patients who recieved treatment with molnupiravir, along with enhanced clearance of infectious virus. The authors conclude that, while this study had a small sample size, this evidence suggests that molnupiravir is a safe and efficacious treatment for mild-to-moderate COVID-19 in non-hospitalized immunocompromized patients.
The second article, co-authored by Dr. Andre Kalil, takes a different approach by targeting the immune response to SARS-CoV-2 infection instead. Severe COVID-19 pneumonia can cause elevated production of a human protein called IL-33 by the immune system. While meant to enhance immune function, this exaggerated response instead causes excessive damage to the body during severe infection, contributing to the development of Acute Respiratory Distress Syndrome (ARDS). This study examined the efficacy and safety of new drugs aimed at interfering with the IL-33 pathway, among other approaches. While these new medications were not associated with safety concerns, the authors report that there was no improvement in time-to-recovery in patients with severe COVID-19 pneumonia.
The last article, published in The Lancet: Respiratory Medicine also co-authored by Dr. Kalil along with LuAnn Larson, RN, and Dr. Angela Hewlitt, explores the efficacy of adjunct therapy with baricitinib or dexamethasone in addition to a standard COVID-19 medication, remdesivir. Both baricitinib and dexamethasone calm an overactive immune response, though through different means, and have evidence supporting their use during COVID-19. However, a study comparing their efficacy in conjunction with antiviral therapy has not previously been performed. To explore this regimen, the authors conducted a randomized, double-blind, double placebo-controlled trial with patients enrolled at 67 trial sites across the globe. The study found that the addition of baricitinib or dexamethasone to remdesivir resulted in similar rates of mechanical ventilation-free survival by the end of the study period. However, patients administered dexamethasone experienced significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events than those taking baricitinib. The authors conclude, “a more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered”.