Assessment and Incidence Determination of [ME/CFS] Following a SARS-CoV-2 Infection in a Prospective Cohort, 2026, Tack et al

[Nightsong]

Background and Objectives: 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.

Materials and Methods: 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).

Results: 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).

Conclusions: 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.

Link | PDF (Medicina, March 2026, open access)

 

[DMissa]

Haven’t had time to dig into the methodology but this seems like it might be an important bit of work. CCC is a good sign

 

[SNT Gatchaman]

Small numbers but here are some summary quotes from results —

The clinical assessment and subsequent laboratory investigations did not reveal any alternative explanation for the reported symptoms in any participant. Accordingly, all assessed individuals (19/19) were classified as having PCS. Within the HALE-cohort, 36.8% (7/19) were classified as having PCS with a diagnosis of ME/CFS (PCS-ME/CFS) and the remaining 63.2% (12/19) were classified as having PCS without ME/CFS (PCS-nonME/CFS).

The overall Bell-score was a median of 60 (range 40–90) out of 100, for PCS-ME/CFS it was a median of 60 (IQR 10.0, range 40–80) and for PCS-non-ME/CFS a median of 65 (IQR 12.5, range 40–90). The CCC involved 38 questions; on average, 16.37 (SD 6.85) questions were answered positively, and the highest number for a participant was 33. Extrapolation for the large cohort (n = 221) shows that at least 3.2% (7/221, CI 95% 1.3–6.4) fulfill the CCC for a diagnosis of ME/CFS, based on a staged subset of participants: 26 participants with persistent fatigue, 19 who underwent further assessment including the CCC, and 7 who ultimately met the full criteria.

In the orthostatic test, 1 HE (1/19) was diagnosed with POTS and 21.0% (4/19) with OH. The mean score of 25.63 points in the MoCA tests was below normal (SD 2.97, range 20–30 points), with 42.1% (8/19) of HEs having results below the cut-off. HEs with ME/CFS had a lower mean value of 24.90 (SD 3.18) compared to those without (mean 26.10, SD 2.87).

In the SFN screening questionnaire, 26.3% (5/19) reported burning pain in extremities, 52.6% (10/19) reported sensory disorders, 36.8% (7/19) reported sleep disorders due to pain, 26.3% (5/19) reported pain increases at night, and 47.4% (9/19) reported hyperesthesia. All five items were negated by 36.8% (7/19). On average, 1.89 (SD 1.88) items were positive. Participants with ME/CFS had higher mean results, with 3.29 (SD 1.70), compared to those without (mean 1.08, SD 1.51). A total of 71.4% (5/7) of those with ME/CFS reported all items except burning pain in extremities.

Routine coagulation markers (Quick, International Normalized Ratio and thrombin time) showed no abnormalities, and Partial Thromboplastin Time was decreased in one HE. Determination of APR demonstrated increased fibrinogen in 16.7% (3/18), increased factor VIII in 16.7% (3/18), and decreased antithrombin in 11.1% (2/18). VWF was possibly increased in 33.3% (6/18), with increased activity or antigen in one BG category. Elevated VWF activity or antigen ( ≥ 1 increased value in each BG category) was seen in 22.2% (4/18).

Additionally, homocysteine concentration was 13.0 µ mol/L (reference value < 10, IQR 2.3) at median and thus increased in 77.8% (7/9) of HEs.

Blood samples were collected and frozen at −80°C for further determination of GPCR AABs. GPCR AABs were determined by IMD Institut für Medizinische Diagnostik BerlinPotsdam GbR laboratory (Berlin, Germany) with specific commercial sandwich ELISA kits (CellTrend GmbH (Luckenwalde, Germany)) for quantitative determination according to the manufacturer’s instructions.

AAB levels against M3R were increased in 88.9% (16/18) and those against ß2-adr-R increased in 66.7% (12/18). AABs against M4R and AT1R were each elevated in 22.2% (4/18). The results for all eight AABs combined for each HE were considered low-grade increased in 44.4% (8/18) and increased in 22.2% (4/18).

The serological status consistent with a possible EBV reactivation was determined based on ≥ 1 positive IgG or IgM antibodies against EA and IEA in 86.7% (13/15).