The heightened inflammatory response observed in COVID-19 patients suggests that omega-3 fatty acids (O3FA) may confer anti-inflammatory benefits. This randomized, double-blind, single-center clinical trial aimed to evaluate the effect of O3FA supplementation in parenteral nutrition (PN) on inflammatory markers in COVID-19 patients admitted to the intensive care unit (ICU). A total of 69 patients were randomized into three groups: one received standard lipid emulsion, and two received O3FA (Omegaven^®) at doses of 0.1 g/kg/day and 0.2 g/kg/day, respectively, in addition to Smoflipid^®. The primary outcomes measured were serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) on days 1, 5, and 10 of PN initiation. Secondary outcomes included additional inflammatory markers (TNF-α, IFN-γ, IL-1Ra, CXCL10), hepatic function, triglyceride levels, and clinical outcomes such as mortality and length of ICU and hospital stay. Results indicated a significant reduction in CRP, IL-6, and CXCL10 levels in the group receiving 0.1 g/kg/day O3FA compared to the control. Additionally, the higher O3FA dose was associated with a shorter ICU and hospital stay. These findings suggest that O3FA supplementation in PN may reduce inflammation and improve clinical outcomes in critically ill COVID-19 patients.

Expanded CD4+CD28^null T lymphocytes are found in the tissues and peripheral blood of patients with many autoimmune diseases, such as rheumatoid arthritis (RA). These highly differentiated cells present potent inflammatory activity and capability to induce tissue destruction, which has been suggested to predispose to the development of more aggressive disease. In fact, preferential migration to inflammatory sites has been proposed to be a contributing factor in the progression of autoimmune and cardiovascular diseases frequently found in these patients. The functional activity of CD4+CD28^null T lymphocytes is largely dependent on interleukin 15 (IL-15), and this cytokine may also act as a selective attractor of these cells to local inflammatory infiltrates in damaged tissues. We have analysed, in RA patients, the migratory properties and transcriptional motility profile of CD4+CD28^null T lymphocytes compared to their counterparts CD28+ T lymphocytes and the enhancing role of IL-15. Identification of the pathways involved in this process will allow us to design strategies directed to block effector functions that CD4+CD28^null T lymphocytes have in the target tissue, which may represent therapeutic approaches in this immune disorder.