Evidence supporting the use of rintatolimod is deemed low to moderate. The US FDA has denied commercial approval, called a new drug application, citing several deficiencies and gaps in safety data in the trials, and concluded that the available evidence is insufficient to demonstrate its safety or efficacy in CFS. Rintatolimod has been approved for marketing and treatment for persons with CFS in Argentina, and in 2019, FDA regulatory requirements were met for exportation of rintatolimod to the country. Rintatolimod is currently in an experimental trial in the USA to treat both ME/CFS and Long Covid. Prognosis
Information on the prognosis of CFS is limited, and the course of the illness is variable. According to the NICE guideliene, CFS "varies in long-term outlook from person to person." Complete recovery, partial improvement, and worsening are all possible. Symptoms generally fluctuate over days, weeks, or longer periods, and some people may experience periods of remission. Overall, "many will need to adapt to living with ME/CFS." Some people who improve need to manage their activities in order to stay improved. Children and teenagers are more likely to recover or improve than adults.A 2005 systematic review found that for untreated CFS, "the median full recovery rate was 5% (range 0–31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8–63%)," and that 8 to 30% of patients were able to return to work. Age at onset, a longer duration of follow-up, less fatigue severity at baseline, and other factors were occasionally, but non consistently, related to outcome.
Increased levels of cytokines have been proposed to account for the decreased ATP production and increased lactate during exercise; however, the elevations of cytokine levels are inconsistent in specific cytokine, albeit frequently found. Similarities have been drawn between cancer and CFS with regard to abnormal intracellular immunological signaling. Abnormalities observed include hyperactivity of Ribonuclease L, a protein activated by IFN, and hyperactivity of NF-κB. Endocrine
Evidence points to abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) in some, but not all, persons with CFS, which may include slightly low cortisol levels, a decrease in the variation of cortisol levels throughout the day, decreased responsiveness of the HPA axis, and a high serotonergic state, which can be considered to be a "HPA axis phenotype" that is also present in some other conditions, including post-traumatic stress disorder  and some autoimmune conditions. It is unclear whether or not decreased cortisol levels of the HPA axis plays a primary role as a cause of CFS, or has a secondary role in the continuation or worsening of symptoms later in the illness. In most healthy adults, the cortisol awakening response shows an increase in cortisol levels averaging 50% in the first half-hour after waking. In people with CFS, this increase apparently is significantly less, but methods of measuring cortisol levels vary, so this is not certain. Autoimmunity
Autoimmunity has been proposed to be a factor in CFS, but there are only a  few relevant findings so far.