Abstract
To identify ICD-10-GM codes recorded in the year preceding a Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) diagnosis, we conducted a 1:5 matched case–control study using statutory health insurance data of 6–27-year-olds with ME/CFS (ICD-10-GM: G93.3, 2020–2022). Cases (n = 6,077) were matched 1:5 to controls by birth year, sex, and postal code. ICD-10-GM codes from the preceding year were analyzed using multivariable conditional logistic regression, reporting odds ratios (OR) and 95% confidence intervals. Most cases were female and aged 18–27 years. Forty-four ICD-10-GM code classes were associated with increased and four with decreased odds, spanning 13 diagnostic chapters. Most associations were in chapters F (mental/behavioral disorders), R (respiratory diseases), and M (musculoskeletal disorders). Frequent conditions included fatigue, depression, pain disorders, and somatoform disorders (≥ 10% in cases; ORs 1.11–2.19. Rare diagnoses (≤ 1% prevalence), such as fibromyalgia (OR 2.08, 95% CI: 1.20–3.59) and mild cognitive impairment (2.93, 1.21–7.10), were strongly associated. Four COVID-19 or vaccination-related code classes were identified, with post-COVID-19 condition showing the highest OR (3.84, 2.97–4.98). Several ICD-10-GM codes, including COVID-19 related codes, were associated with later ME/CFS diagnoses. Prospective studies should clarify timing relative to ME/CFS onset, and distinguish between pre-existing conditions, comorbidities, early manifestations, or misdiagnoses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-40848-1.