There are several factors in this research effort which either match or differentiate problems of astronauts and ME/CFS patients. One strong similarity is orthostatic intolerance due to inactivity. Astronauts show this so strongly on return that some have needed to be carried when first back in a one-gee environment. Another is
reactivation of herpes viruses, though this stays below the threshold usually set for diagnosing active herpes infections, unless you go looking for evidence. A third similarity is the parallels between physical deterioration and cognitive impairment.
Differences: 1) all astronauts pass rigorous physical and psychological screening, and don't fly unless they are in excellent condition; 2) even low-Earth orbits below the Van Allen belts are subject to increased radiation exposure, which you do see in pilots and crew of jet aircraft, but not in patients; 3) nobody doubts that astronauts are motivated to return to good physical performance.
Even with all the normal explanations removed, it still takes something like a year to recover from prolonged spaceflight in microgravity ("zero gee"). A few weeks of graded exercise therapy would not do. There are also signs that immune system activation takes place both on entry into the space environment and on return to Earth surface environment. You might explain the first by low-level radiation exposure, which is known to increase immune activation in the short term, but this fails badly to explain activation on return.
What definitely does change is circulatory function, particularly venous return to the heart, which is mostly driven by contractions of leg muscles and tiny valves in veins. No matter how large arterial pressure changes may be, very little of this will make it through capillaries to move venous blood. In this sense people in microgravity environments resemble those in
the study by David Systrom's group who had measurable low ventricular filling pressures. Problems on return to Earth would be a natural result of atrophy of this function.
Now I'm going to go out on a limb and speculate on something that seems obvious from a physics perspective. Immune cells aren't very good at swimming. They depend on blood circulation to move them to distant parts of the body and back to communicate with other immune cells. The time to respond to an immune challenge and the efficiency with which a system produces the specific response needed, where it is needed, is obviously dependent on the rate of transport. If I were thinking in terms of a system of differential equations describing immune performance, when we know that specialized cells do quite a bit of communication with other specialized cells, not necessarily of the same type, I would expect circulatory function to be a major factor in immune health. In cases of heart failure this is matched by clinical observations.
ME/CFS patients regularly have cardiac output in the same range as patients with heart failure, but mainly when upright, which is seldom measured. This is not counted as heart failure because these patients can recover by lying down, which is not true of patients with true heart failure.
I'm postulating that this episodic impairment of circulatory function also affects immune function, which can lead to reactivated viral infections and misdirected immune responses.