Assessment and Incidence Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees

<i>Background and Objectives</i>: Post-COVID-19 syndrome (PCS), characterized by persistent fatigue, can develop after a SARS-CoV-2 infection. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, post-infectious condition marked by severe fatigue and post-exertional malaise. This study aimed to determine the incidence and characteristics of PCS and ME/CFS in a cohort of hospital employees (HEs) with SARS-CoV-2 infections. <i>Materials and Methods</i>: All HEs who tested SARS-CoV-2-positive between March 2020 and May 2021 who later reported persistent fatigue were invited for an assessment from July to December 2022. Canadian Consensus Criteria were used for the diagnosis of ME/CFS. Assessments included the Montreal Cognitive Assessment (MoCA), and determination of coagulation factors, Epstein-Barr virus (EBV) antibodies and autoantibodies (AABs) against G-protein-coupled receptors (GPCRs). <i>Results</i>: Of the 221 HEs, 11.8% (95% confidence interval (CI95%) 7.8-16.8, 26/221) still reported persistent fatigue and 3.2% (CI95% 1.3-6.4, 7/221) were diagnosed with ME/CFS. In total, 19 HEs (median age 51.0 years, 89.4% female, 63.1% possible or confirmed nosocomial infection) participated in our assessment. In 42.1% (8/19) MoCA results were below normal. Laboratory values showed increased GPCR AABs in 66.6% (12/18), possible EBV reactivation in 86.7% (13/15) and coagulation parameters suggesting inflammatory processes in 38.9% (7/18). <i>Conclusions</i>: Our study was able to determine lower-bound incidences of PCS with fatigue and ME/CFS and demonstrated a diagnostic pathway for HEs following SARS-CoV-2 infections. Possible EBV reactivation, increased GPCR AABs and potential coagulation cascade activation may play a pathogenic role.