One of the problems in targeting treatment is that underlying pathophysiology is not understood. What is now called ME/CSF was first described in the 1930s when poliomyelitis was a suggested cause. In 2020, causes and/or triggers of ME/CSF can still only be theorised; the NHS Health A to Z lists viral infections (eg glandular fever), bacterial infections (eg pneumonia), immunological disorders, hormonal imbalance, mental health problems, or genetics.12,20

One theory is that long COVID symptoms may actually be due to different syndromes, such as post-intensive care syndrome, post-viral fatigue syndrome and long-term COVID syndrome. Some people may also experience more than one syndrome at a time.27

Another possible mechanism is that SARS-CoV-2 triggers autoimmune responses, with some people genetically predisposed to producing autoantibodies blocking the action of type 1 interferon molecules and/or B cells.28

NICE recognises that long COVID is a dynamic area; NG188 will be reviewed continuously and updated as new evidence emerges.4