Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan. — CFSMEATLAS
Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan.
Morita, Satoru, Tokumasu, Kazuki, Otsuka, Yuki et al. · PloS one · 2024 · DOI
Quick Summary
This study looked at 739 patients with long COVID to understand how many developed ME/CFS and what factors were involved. Researchers found that ME/CFS affected about 8% of long COVID patients, but the rate varied depending on which COVID variant caused the initial infection—it was much higher (24%) in early COVID but dropped significantly (3%) during the Omicron wave. Brain fog complaints increased over time, even as strict ME/CFS diagnoses became less common.
Why It Matters
Understanding variant-dependent patterns in long COVID-related ME/CFS is crucial for clinicians to recognize and diagnose the condition accurately, particularly as dominant variants change. This research highlights that subjective symptoms like brain fog may persist or even increase even when formal ME/CFS criteria are met less frequently, suggesting evolving phenotypes that warrant continued clinical attention and research.
Observed Findings
ME/CFS prevalence among long COVID patients declined from 23.9% (pre-Delta) to 13.7% (Delta) to 3.3% (Omicron phase)
Patients with ME/CFS had lower vaccination rates overall and higher rates of severe initial illness, smoking, and alcohol use
Fatigue and headache were the most common complaints in ME/CFS patients across all periods
Serum ferritin levels were significantly elevated in female ME/CFS patients infected during the pre-Delta period
Inferred Conclusions
COVID variant type influences both the frequency of ME/CFS diagnosis and the symptom profile of long COVID patients
Brain fog and subjective cognitive complaints are increasingly prominent features of long COVID across variants, even when strict ME/CFS criteria are less frequently met
Vaccination status and severity of acute infection are associated with reduced ME/CFS risk in long COVID
ME/CFS related to long COVID shows variant-dependent epidemiological and clinical trends requiring attention to evolving phenotypes
Remaining Questions
What mechanistic differences between variants explain the declining prevalence of ME/CFS despite persistent or worsening brain fog symptoms?
What This Study Does Not Prove
This study does not prove that COVID variants cause ME/CFS through different mechanisms, nor does it establish causation for the identified risk factors (smoking, alcohol, vaccination status). The retrospective design cannot eliminate confounding from changes in diagnostic awareness, variant-specific disease biology, or population differences over the study period. Cross-sectional data cannot track individual symptom progression or recovery patterns.
Do the subjective cognitive symptoms in Omicron cases represent true ME/CFS that does not meet formal criteria, or a distinct post-COVID syndrome?
How do vaccination timing, type, and dosing specifically relate to ME/CFS development in long COVID?
What is the long-term trajectory of patients with long COVID brain fog who do not meet formal ME/CFS criteria—do they recover, develop chronic conditions, or progress to ME/CFS?