Virology and Post-Infectious Mechanisms
1 Herpesvirus Reactivation and Anti-dUTPase Antibodies
Principal Investigator:: Mar{'}a Palomo and collaborators
Institution:: Multi-centre (Spain / USA)
Contact/URL:: https://doi.org/10.1002/jmv.70769
Funder:: Institutional
Status:: Published 2026
Phase:: Observational (case-control)
Cohort:: ME/CFS patients + healthy controls
Mechanism/Focus:: Measured antibodies to EBV, HHV-6, and VZV, plus anti-dUTPase IgG (a marker of active herpesvirus replication). 72.5% of ME/CFS patients simultaneously co-expressed antibodies to multiple herpesviruses versus 31% of controls. Heightened herpesvirus antibody levels clustered with moderate-to-severe fatigue.
Primary Outcomes:: Multi-herpesvirus co-reactivation as hallmark of post-infectious ME/CFS; anti-dUTPase IgG as fatigue-associated marker
Estimated Completion:: Published
Publication Medium:: Journal of Medical Virology
Document Relevance:: Ch. 7 (immune dysfunction), Ch. 9 (infection and triggers), Ch. 20 (biomarker research)
The simultaneous co-reactivation of three herpesviruses in over 70% of patients suggests systemic immune surveillance failure rather than reactivation of a single pathogen (Palomo et al. 2026). The anti-dUTPase antibody is mechanistically interesting because dUTPase is an enzyme conserved across herpesviruses that can directly activate innate immune signalling. If validated as a stratification marker, it could identify a “viral reactivation” subtype amenable to antiviral or immunomodulatory therapy.
2 Post-IM Longitudinal Cohort: Seven-Year Follow-Up
Principal Investigator:: Ben Z. Katz, MD
Institution:: Northwestern University / multi-site (USA)
Contact/URL:: https://doi.org/10.3389/fmed.2026.1676628
Funder:: NIH
Status:: Published 2026
Phase:: Observational, prospective longitudinal cohort
Cohort:: 4,501 college students enrolled before developing infectious mononucleosis (IM); followed for 7 years
Mechanism/Focus:: Uniquely prospective design: baseline data collected at least 6 weeks before IM onset. Tracks natural history from pre-infection through ME/CFS development, enabling identification of pre-existing risk factors.
Primary Outcomes:: ME/CFS incidence: 13% at 6 months, declining to \(\sim\) 4% at 24 months post-IM. Risk factor identification at 7-year endpoint
Estimated Completion:: Published
Publication Medium:: Frontiers in Medicine
Document Relevance:: Ch. 9 (infection and triggers), Ch. 23 (epidemiology), Ch. 14 Speculative Cross-Disease Connections (post-viral overlap)
This is one of the few truly prospective studies in ME/CFS, with pre-infection baseline data that enables causal inference about risk factors—a design strength shared with the DecodeME genetic study (Section Genomics and Epigenetics). The declining incidence from 13% to 4% over two years suggests spontaneous recovery in most post-IM ME/CFS cases, but the persistent 4% represents a “locked-in” subset of particular clinical and research interest (Katz et al. 2026).
3 RECOVER ME/CFS Incidence Study
Principal Investigator:: RECOVER Consortium
Institution:: NIH multi-site (USA)
Contact/URL:: https://doi.org/10.1007/s11606-024-09290-9
Funder:: NIH RECOVER Initiative
Status:: Published 2025
Phase:: Observational (adult cohort)
Cohort:: Large-scale RECOVER-Adult observational study
Mechanism/Focus:: Determined incidence and prevalence of ME/CFS following SARS-CoV-2 infection. Applies established diagnostic criteria to the largest prospective post-COVID cohort.
Primary Outcomes:: Confirmed that ME/CFS incidence increases following SARS-CoV-2 infection; provides population-level estimates
Estimated Completion:: Published
Publication Medium:: Journal of General Internal Medicine
Document Relevance:: Ch. 9 (infection and triggers), Ch. 23 (epidemiology), Ch. 14 Speculative Cross-Disease Connections
This study provides the strongest epidemiological evidence to date that SARS-CoV-2 infection increases ME/CFS incidence, confirming a pattern previously observed with EBV, Ross River virus, and Coxiella burnetii (Jason et al. 2025). The RECOVER infrastructure’s scale enables subgroup analyses by demographics, infection severity, and vaccination status that smaller cohorts cannot support.