Long COVID, generally defined as clinical symptoms persisting for 3 months or longer following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, affects multiple organs and systems. At least 400 million people globally are living with long COVID, with symptoms including persistent fatigue and brain fog. Currently, long COVID care mainly consists of symptomatic management and supportive approaches, with no validated effective treatments available that address the underlying inflammation. Stem Cell Educator (SCE) therapy is a treatment developed to modulate immune responses. This protocol describes SCE therapy and its application in patients with long COVID to evaluate safety, clinical outcomes, and immunological changes. During SCE therapy, a patient's peripheral blood mononuclear cells (PBMC) are collected by leukapheresis and co-cultured with adherent cord-blood-derived multipotent stem cells (CB-SC) in vitro, after which the "educated" PBMC are returned to the patient's circulation via infusion. SCE therapy has previously been evaluated in clinical studies for type 1 diabetes and other autoimmune diseases. Twenty-five patients with long COVID (15 males and 10 females) received SCE therapy. Five patients experienced mild adverse effects during apheresis, and one patient reported itching during infusion. Brain fog and fatigue disappeared in 21 of 25 patients following treatment, and most participants reported feeling refreshed, energized, and mentally clear. Flow cytometry demonstrated reductions in inflammatory markers, including interleukin-1 beta (IL-1β)-positive cells and C-X-C motif chemokine ligand 16 (CXCL16)-positive cells. These findings demonstrate the application of SCE therapy in patients with long COVID and provide preliminary clinical and immunological observations supporting further evaluation of this approach.
