Mednotes

L2 Early Professional Experience Insights into ME_ CFS and long COVID

Properties2
tagsearlyprofessionalexperience, lecture, mecfs, longcovid
aliasesInsights into ME/CFS and long COVID

18 min read

Overview

A lecture by Emeritus Professor Warren Tate (Department of Pathology, University of Otago) on the two post-viral/stressor syndromes ME/CFS and Long COVID, and on how doctors should manage the patients who have them. It moves through four linked parts: what a post-viral syndrome is and why there are now two of them (epidemiology, history, naming); what the illness looks like lived from the inside (a 35-year family case history, symptoms, disease course); what a decade of multi-omic and genetic research says about the underlying pathophysiology; and finally what patients report they need from clinicians, which treatments patients say help, and a proposed integrated view of overlapping complex chronic conditions. The through-line is that ME/CFS and LC are largely the same illness arriving by different routes, and that the main deficit patients face is not just biology but disbelief and poor clinical knowledge.

Aims of the session

  • A: develop an understanding of the complexities of the post-viral fatigue syndromes ME/CFS and Long COVID, and of the relationship between them.
  • B: appreciate how you, as emerging doctors, could ensure better patient care and medical management for affected patients and their families.

Key points the lecture addresses:

  1. What a post-viral/stressor syndrome is, and why there are two of them (ME/CFS and LC). Illustrated by a 35-year case study of the presenter’s daughter (used with her permission) and by a very severe case currently in Dunedin hospital.
  2. What the pandemic-related LC experience has taught us about better managing long-term ME/CFS patients.
  3. How these and other complex chronic syndromes can best be managed medically and socially today.

Post-viral syndromes in context: who gets them and how many

Outcomes after a viral infection or a major stressor split by susceptibility:

  • The susceptible 5 to 10%. Viral infection or major stress leads to a post-viral syndrome; the majority of those go on to a lifelong ongoing illness, ME/CFS. Around 30,000 people in NZ.
  • The rest of the population. About 70% recover within 0 to 2 weeks; the other 30% recover over up to a few months.

After the COVID pandemic (SARS-CoV-2):

  • More than 800 million cases worldwide.
  • An estimated more than 100 million cases of Long COVID currently.
  • NZ LC numbers are not known; possibly up to 150,000 based on global incidence.

Population prevalence of these major lifelong debilitating illnesses is given as 0.4 to 2% of the population.

What ME/CFS is, and where the names come from

A debilitating fatigue illness described as far back as the 18th century BC by a Mesopotamian philosopher; Florence Nightingale (19th century AD) and Charles Darwin were likely affected.

Over the last 100 years, in susceptible people, it:

  • arose from “boutique” infectious disease outbreaks of a few thousand cases;
  • was drip-fed from endemic viral infections such as glandular fever and influenza;
  • attracted little global attention or research investment.

The condition has been given many names. The composite name ME/CFS settled in around 2016:

  • ME from the London outbreak of 1955.
  • CFS from the Nevada outbreak of 1984 (Incline Village, Crystal Bay, on the Nevada/California border).

Other causes. ME/CFS can develop from causes other than viral infection: other infectious agents, agricultural chemicals, surgery, and chronic severe stress. These account for roughly 20% of cases.

NZ’s own boutique outbreak was “Tapanui flu” in 1984 (lower South Island), 28 cases, now in medical folklore.

The presenter’s first exposure was the dramatic onset in 1990 of pervasive fatigue in his 14-year-old daughter, a few months after an attack of glandular fever. Medical practitioners in Dunedin at the time seemed to know nothing of the disease, and the default view freely given was that it was likely a psychological “perception” disorder.

Long COVID: naming, definition and heterogeneity

Long COVID first appeared in 2020 as the SARS-CoV-2 post-viral syndrome; “Long COVID” is the generally accepted populist name. Other names:

  • Post-acute Sequelae of SARS-CoV-2 infection (PASC), the clinical name
  • Post-COVID condition (WHO)
  • Post-acute COVID
  • Long haul COVID

Case definition. In October 2021 the WHO ran an iterative process with 250 contributors, including patients, to derive a clinical case definition for LC.

Core symptoms, remarkably similar to those of ME/CFS: fatigue, post-exertional malaise, brain fog (cognitive dysfunction), unrefreshing sleep, pain, breathlessness.

Long COVID as understood in 2026. The name is given to anyone who has not recovered within 3 months of COVID, but the patient group is heterogeneous and includes people with organ damage as well as people with an ME/CFS-like syndrome. Gentilotti et al 2023 (eClinicalMedicine) classify LC into four patient groups:

GroupShare
ME/CFS-like syndrome42%
Respiratory syndrome from lung damage23%
Pain syndrome21%
Neurosensory syndrome (loss of taste, smell)11%

Relationship between the two conditions. Both ME/CFS and LC patients report more than 200 symptoms, of which 95% overlap. Each patient has the 5 core symptoms plus a number of others but not all of them, which produces extensive patient heterogeneity and makes diagnosis difficult for clinicians.

Symptoms and course of ME/CFS

Symptoms:

  • Debilitating fatigue
  • Brain fog (cognitive dysfunction)
  • Post-exertional malaise, meaning relapse after physical, mental or emotional activity
  • Unrefreshing sleep
  • Irritable bowel, GI upsets, food allergies
  • Hyper-sensory perception (light, sound)
  • Pain
  • Poor brain regulation of body physiology, and dysautonomia

Disease course:

  • For the presenter’s daughter, as for the 95% affected, it is a lifelong illness (35 years to date).
  • 25% are housebound.
  • 75% move to a chronic phase in which they can have limited interaction in their communities, suffer frequent relapses, and the vast majority cannot work.

The case history section poses the questions of how the illness has affected the daughter’s life over 35 years and how she and the family have interacted with the medical system, compared briefly with a very severely debilitated currently hospitalised patient.

Pathophysiology: the multi-omic model

Ten years of multi-omic research (research team 2013 to 2022: Tina Edgar, Dr Eiren Sweetman, Alex Noble, Dr Angus Mackay; current team 2024 to present: Sayan Sharma, Dr Katie Peppercorn), published in Frontiers in Neurology in 2022, found defects across different molecular classes in:

  1. Immune/inflammatory pathways
  2. Energy production/mitochondrial function
  3. Metabolism (low)
  4. Oxidative stress
  5. Neural function
  6. Circadian molecular clock

The published model runs as follows:

  1. A trigger, one of micro-organism, toxic chemical, stress, virus, or surgery, causes an initial event.
  2. The initial event produces a peripheral immune/inflammatory response.
  3. From that response, three branches lead onward: the inflammatory reflex, an increase in blood-brain barrier permeability (BBBP), and the gateway reflex. Three further consequences run alongside: chronic serotonin release, chronic HPA axis dysfunction, and disturbed homeostasis.
  4. The three branches, together with PVN dysfunction, converge on fluctuating neuroinflammation, which is the chronic ME/CFS / Long COVID state.
  5. Fluctuating neuroinflammation produces the symptoms: fatigue, brain fog, pain, unrefreshing sleep, post-exertional malaise.
  6. An external life stressor feeds back into the peripheral immune/inflammatory response as a relapse arrow.

The presenter’s own trajectory maps onto this work in three phases: Phase I as an ME/CFS parent (1990 onwards), Phase II as a biomedical researcher (2012 to present), Phase III as a COVID-era patient “counsellor” (2020 to present), running 1990 (daughter’s illness) to 2012 (started research) to 2022 (a holistic model).

Genetics and current research

Current work (2026): epigenetic DNA methylome changes as the basis for an early diagnostic test, and a genetic risk signature for families. Researchers named: Galina Mandich (now 5th year medical student) and Sayan Sharma (PhD student).

A genetic link for susceptibility to ME/CFS. Das et al, Journal of Translational Medicine (2022), with Precision Life, Oxford, reported:

  • SNPs falling into 15 clusters of 3 to 5 SNPs each
  • 14 associated genes
  • 91% predictive ability on ME/CFS samples tested from the UK Biobank

Summer students Bryn Griffiths and Galina Mandich (2024 to 2026) worked on this; Galina Mandich worked over the summer on samples from a single family to derive a family risk signature. The family sequencing data shown (primer 6, rs58264436) had two unaffected family members homozygous A at the variant position (TACAAATATC) while the two affected members carried a heterozygous A/G call (TACAA/GATATC).

Transcript flags on this slide: one bullet reads only "4th year medical student ov" and is cut off/incomplete as printed, and the network plot of clusters 1 to 15 is unlabelled beyond the cluster numbers, so the identity of individual nodes is not given.

The plight of a patient today

  • Still a lack of knowledge and understanding of both ME/CFS and Long COVID among many health professionals, exemplified by a patient in hospital currently.
  • Major lifelong debilitating illnesses affecting a lot of people (0.4 to 2% of the population).
  • Still an equivocal attitude from family, friends and even health practitioners as to whether this is a “real illness”; this has gradually decreased with time but sadly is still present.
  • ME/CFS is classified as a chronic illness, which does not allow good access to social services and financial services, despite patients being seriously debilitated from day 1.

What treatments are available, and what patients report

The tools available are drugs, nutraceutical supplements, and behavioural or relaxation therapies. The evidence shown comes from the TreatME survey (Open Medicine Foundation, July 2025) of 4,000 ME/CFS and LC patients across 150 mainly drugs and supplements. Each treatment is reported as (n | statistical value | percentage of patient responses):

Treatmentnvalue%
Fluids/electrolytes30531.0e-17168.6
Pacing8037.1e-12275.2
Compression stockings9526.3e-7762
Antihistamines29821.3e-6751.6
Nattokinase/Lumbrokinase9059.9e-3849.9
Low-Dose Naltrexone9512.2e-3749.4
Beta blockers or ivabradine11292.5e-3447.1
Melatonin9872.3e-2343.3
Other select MCAS treatments11311.8e-1739.7
Intravenous/subcutaneous immunoglobulin916.5e-1358.2
Vitamin B-1215051.5e-1236
Manual lymphatic drainage976.1e-1255.7
Rx anticoagulants and/or antiplatelets2702.3e-1143.7
ADHD stimulants (Rx)3271.0e-1041.6
Maraviroc581.3e-0856.9
Mestinon2511.3e-0841
Coenzyme Q1017791.7e-0833
Vagal nerve stimulation1324.7e-0845.5
Palmitoylethanolamide1714.9e-0741.5
Curcumin6107.6e-0734.4
Vitamin C (oral, NOT liposomal), boxed on the slide14540.523824.1
Graded exercise therapy, set apart below the chart2991.0000-72.2

Pacing has the highest percentage of patient responses (75.2%), and fluids/electrolytes the largest sample (n = 3053). Graded exercise therapy is shown separately, with a negative value of -72.2%, and its bar sits at the opposite end of the scale from every treatment above it; the slide singles it out with the label “GRADED exercise therapy”.

Transcript flag: the chart's colour legend is not shown on the slide, so the meaning of each colour band (for example degree of benefit versus harm) is not stated. The negative value for graded exercise therapy is recorded as printed, without interpretation.

What patients are asking of you

From excerpts of the report to the Ministry of Health, “Impacts of COVID-19 in Aotearoa” (Health Services Research Centre, VUW, January 2023), Long COVID patient survey. Patient comments:

  • Lack of understanding by health professionals.
  • Lack of information, and being misinformed, which contributed to patient burden.
  • A desire for their doctors to be more pro-active.
  • About 50% said that as affected patients they had inadequate health or social care.
  • They needed clear clinical pathways, better communication, and better informed doctors with a path to their improvement.
  • They wanted to be heard, and to be believed.

What you could do for an ME/CFS or LC patient

  • Affirm their illness, even if you do not understand it, and recognise ME/CFS or LC as a possibility; this develops patient/clinician trust.
  • Listen to the patients. They know a lot about how the condition affects their lives and their families, and they are gracious if shown empathy.
  • Appreciate the stress on the family and realise the family will need support. There are now social media groups for the conditions and a small number of highly functioning support groups throughout the country.
  • Know the management strategies available that might best help your patient, for example a “Concise Review for Clinicians”.

The single most requested thing from patients is to be heard and believed. Affirming the illness and recognising ME/CFS or LC as a possibility costs nothing and is the foundation of the therapeutic relationship, even where you cannot explain the biology.

References given for management:

  • Grach et al 2023, Diagnosis and management of ME/CFS, Mayo Clinic Proceedings 98:1544-1551.
  • Kujawski et al 2026, International Expert Consensus on Objective Measures for Diagnosing ME/CFS and Long COVID, submitted to Lancet Neurology.

Resources and expertise named in the lecture: NZ’s clinical expert GP for ME/CFS, Dr Ros Vallings (now retired), author of “Chronic Fatigue Syndrome M.E.: Symptoms, Diagnosis, Management” (fully revised and updated) and “Managing ME/CFS: A guide for young people”; and “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Methods and Protocols” edited by Warren P. Tate and Katie Peppercorn (Springer Protocols, Methods in Molecular Biology 2920, Humana Press), published May 2025.

A vision for the future: integrated management of overlapping chronic conditions

The proposal is that all complex chronic conditions with significant overlap in symptoms and similar co-morbidities be regarded in an integrated manner.

Conditions grouped around a shared core of common symptoms:

Co-morbidities named:

The common symptoms shared across the five conditions: cognitive impairment, unrefreshing sleep, digestive issues, dysautonomia, extreme fatigue, muscle pain, depression, headaches, joint pain, anxiety.

Reference: Tate et al 2025, Managing chronic fatigue conditions with overlapping symptoms and the health policies and social services supporting those affected, Medical Research Archives of the European Society of Medicine 13(11).

Self-test

  1. Describe what happens to the population after a viral infection or major stressor, giving the proportions for each outcome group.
  2. State the estimated number of people with ME/CFS in NZ, and the estimated worldwide number of Long COVID cases.
  3. Explain where the two halves of the name “ME/CFS” come from, and when the composite name settled.
  4. List the causes of ME/CFS other than a viral trigger, and give the proportion of cases they account for.
  5. Define Long COVID as the term is used in 2026, and list its other names.
  6. List the four patient groups into which Long COVID is now classified, with the share of patients in each.
  7. Explain why Long COVID and ME/CFS are considered remarkably similar, using the symptom data given.
  8. Explain why patient heterogeneity makes diagnosis difficult for clinicians, given that every patient has the core symptoms.
  9. List the core symptoms of ME/CFS.
  10. Define post-exertional malaise.
  11. Describe the disease course of ME/CFS in terms of the proportions housebound, in the chronic phase, and recovering.
  12. List the six molecular classes in which defects were found by the multi-omic research.
  13. Describe, in order, the steps of the 2022 pathophysiological model from trigger to symptoms.
  14. Explain how an external life stressor is accommodated in that model.
  15. State the three findings of the Das et al 2022 SNP study.
  16. Explain what the family sequencing data for rs58264436 showed about the affected versus unaffected family members.
  17. List four features of the plight of a patient developing ME/CFS or LC today.
  18. Explain why classification as a chronic illness disadvantages ME/CFS patients.
  19. Name the two treatments with the highest reported percentage of patient responses in the TreatME survey, and state how graded exercise therapy was reported.
  20. List what Long COVID patients said they needed from the health system in the VUW report.
  21. Describe the four things a clinician could do for an ME/CFS or LC patient.
  22. List the five conditions proposed for integrated management, and the two named co-morbidities.
  23. A 15-year-old presents with pervasive fatigue that began a few months after glandular fever, with unrefreshing sleep, brain fog and relapse after mild exertion. Explain what is happening in terms of the model taught in this lecture, and predict the likely long-term course.
  24. A patient recovering from COVID is still unwell at 4 months with fatigue, post-exertional malaise and brain fog, and normal lung imaging. Explain which Long COVID subgroup this fits and what it implies for management.
  25. Integrative: explain how the pandemic-related Long COVID experience could improve the management of long-term ME/CFS patients, drawing on the epidemiology, the pathophysiology and the patient-reported material.

Answers

Graph View

Backlinks