Glucocorticoids (GCs), a class of corticosteroids, have emerged as one of the primary treatments for severe cases of COVID-19 due to their anti-inflammatory and immunosuppressant properties. Brazilian researchers have now discovered new ways in which these drugs impact the body’s inflammatory response during an infection: they raise levels of endocannabinoids (eCBs), which are molecules produced by the body itself and bind to the same receptor as cannabidiol, and lower blood levels of platelet-activating factor (PAF), a lipid mediator of inflammation and clotting.
The study, published in the journal Viruses, sought to investigate whether patients with mild symptoms of COVID-19 were more protected due to the natural production of these molecules and whether their levels were lower in severe cases leading to exacerbated inflammation and ICU care. The study received support from FAPESP (projects 22/07287-2 and 21/04590-3).
The research team found that levels of endocannabinoids were higher and blood levels of PAF lower in severe patients than mild ones, leaving them to conclude that these biomolecules’ modulation was not caused by the disease but by treatment with glucocorticoids. The researchers observed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression, which revealed that these drugs can alter the activity of enzymes involved in the metabolism of the lipidic mediators analyzed. Leukocytes are white blood cells and part of the immune system.
The novel findings open up opportunities for future treatments not only for COVID-19 but also for severe inflammatory and neurological diseases. They also suggest that cannabinoids, natural or artificial, could be harnessed for adjuvant therapy. Carlos Arterio Sorgi, a professor in the Department of Chemistry at the University of São Paulo’s Ribeirão Preto School of Philosophy, Sciences and Letters, stated that combining the effects of the two compounds would create the best possible scenario.
Future research plans include studying the effects of glucocorticoids on other viral diseases such as flu. The researchers also plan to understand if the organism maintains the same capacity to produce endocannabinoids after vaccination against COVID-19 and during convalescence from the disease. They are also interested in partnering with groups who work with cannabidiol for animal trials as they move into a different phase of COVID-19.
The researchers belong to the ImmunoCovid consortium, which besides the Chemistry Department at FFCLRP-USP also involves the Department of Clinical, Toxicological and Bromatological Analysis at FCFRP-USP, the Departments of Biochemistry and Immunology, Surgery, and Anatomy, and Clinical Medicine at the Ribeirão Preto Medical School (FMRP-USP), and the Department of General and Specialist Nursing at the Ribeirão Preto Nursing School (EERP-USP).
