Research Commentaries

Predictors for Severe ME/CFS

Predictors for Developing Severe ME/CFS Following Mononucleosis

New research, co-authored by Doctors with M.E. honorary fellow Professor Leonard Jason, attempts to identify why some patients develop severe ME/CFS following Infectious Mononucleosis (IM, Epstein Barr or Glandular Fever) by seeking out possible predisposing risk-factors.

Additional gastrointestinal symptoms and abnormal immune markers prior to IM infection appear predispose patients towards developing severe ME/CFS.

“The identification of predisposing risk factors could significantly alter the therapeutic strategies in IM and other triggers of ME/CFS in adults and adolescents. In addition, it may lead to a reappraisal of the ME/CFS diagnostic criteria to include objective GI and/or autonomic criteria for diagnosis.”


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness affecting over a million people in the US. About 9-12% of individuals develop this syndrome six months following Infectious Mononucleosis (IM); those who meet > 1 set of criteria for ME/CFS are termed severe ME/CFS. We sought to determine why some individuals develop ME/CFS following IM while most recover.

Methods: Our study was a prospective cohort study conducted at Northwestern University. We recruited a cohort of college students before, during, and after being infected with IM. Those who developed IM were followed-up with at six months to determine whether they recovered or met criteria for ME/CFS. We explored baseline levels and severity at follow-up of IM variables for those who recovered from IM and those who developed severe ME/CFS 6 months following IM.

Findings: Pre-illness variables that differentiated these groups included baseline gastrointestinal symptoms and certain cytokines. At onset of IM, gastrointestinal symptoms differentiated the two groups.

Interpretation: The differences that emerged predicted the onset of severe ME/CFS following IM. Our research has thus uncovered risk factors predisposing to non-recovery following IM so that preventative and treatment strategies for ME/CFS may now be devised and studied.


Jason, LA., Cotler, J., Islam, MF., Furst, J., Katz, BZ. Predictors for Developing Severe ME/CFS Following Mononucleosis. The Lancet. Published online April 7, 2021.

Prof. Leonard Jason

Honorary Fellow

Professor of Psychology, DePaul University, Chicago, Director, Center for Community Research Director, DePaul University Chronic Fatigue Syndrome Project