One-Year Follow-up of Young People with ME/CFS Following Infectious Mononucleosis by Epstein-Barr Virus

Abstract

Background: Infectious mononucleosis, caused by the Epstein-Barr Virus (EBV-IM), has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Our study presents the first cohort of young individuals in Germany who were diagnosed with ME/CFS following EBV-IM. Methods: We conducted a one-year follow-up of 25 young people diagnosed with ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise and with documented EBV-IM as the triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed at first visit as well as 6 and 12 months later at follow-up visits. Results: The physical functioning and HRQoL of the cohort were significantly impaired, with young adults displaying more severe symptoms, as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, we found that 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS, indicating partial remission, while all young adults continued to fulfill the Canadian consensus criteria. Improvement in children was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults had little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1-34.9) months. Conclusions: ME/CFS following EBV-IM in young people is a severely debilitating disease with diagnoses protracted longer than one year in many patients and only limited responses to conventional symptom-oriented medical care. Although younger children may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed for this very young age group to better manage their medical condition and pave the way to recovery.

The German Multicenter Registry for ME/CFS (MECFS-R)

“…The physical and social functioning of MECFS-R participants was severely reduced as indicated by low Bell and SF-36 scores, while higher scores were found for emotional role functioning and psychological well-being [70,71]. This aligns with earlier reports indicating that the HRQoL of patients with ME/CFS compared to other chronic diseases is severely compromised, mainly due to physical impairment [55,56,68,72] Moreover, in support of published results [73], MECFS-R participants suffered from significant autonomic dysfunction as indicated by high COMPASS-31 scores. We recommend the Bell score, SF-36, and COMPASS-31 as standard measures for clinical phenotyping to facilitate both local medical care as well as future studies with secondary use of MECFS-R data.…”

“…Accordingly, a predominance of SARS-CoV-2 was identified in adults (59.5%) and EBV in pediatric patients (26%) in our first cohort. Non-infectious triggers are most likely underrepresented since both recruiting centers are focusing on post-infectious ME/CFS as immunological departments [55,56,68]. However, the registry allows a very precise documentation of triggering events including clinical and laboratory data from the time of initial symptoms, and therefore facilitates a stratification of study participants along confirmed versus probable and selfreported triggers.…”