Long COVID, ME/CFS, PEM & POTS — explained clearly

Introduction & Summary

This knowledge base pulls together the current, evidence-based state of knowledge on Long COVID / post-COVID, ME/CFS, post-exertional malaise (PEM) and POTS/dysautonomia in plain language. It is aimed at affected people, their relatives and interested professionals who use the mypacing platform — a tool to support energy management (pacing). Important up front: mypacing is not a medical device and replaces neither medical diagnosis nor treatment. These texts inform you; every treatment decision belongs in the hands of a doctor.

The common thread is the interplay of four conditions that overlap strongly in the clinic. Chapters 1–3 lead from the virological basics of SARS-CoV-2 through the definitions of Long COVID (WHO: post-COVID-19 condition; NICE cut-off from week 4 or 12) to the pathophysiology hypotheses discussed today, which probably reinforce one another (viral persistence, immune dysregulation, autoimmunity, endothelial and mitochondrial disturbances). Chapters 4–7 cover ME/CFS with its core symptom PEM, the POTS spectrum of orthostatic intolerance, as well as brain fog and further accompanying symptoms, ordered by pragmatic — not formally validated — subtypes.

The connecting hallmark symptom is PEM: an often time-delayed, disproportionate worsening after physical, mental or emotional exertion, with a prolonged recovery time. It is the central reason why pacing is at the heart of everything. Chapter 8 translates this into non-drug practice (crash triggers, pacing strategies). Chapters 9–10 place the medication options in context — all of them symptom-oriented, mostly off-label and with no curative claim. Chapter 11 makes clear that diagnoses are so far made clinically: there is no routinely available, validated biomarker. Chapter 12 points to guidelines and care structures in Germany and the EU. Chapter 13 looks at MCAS (mast cell activation syndrome), a frequent, often overlooked co-diagnosis that noticeably often occurs alongside POTS, Long COVID and ME/CFS. Chapter 14 turns to the gut-brain axis and the disputed SIBO diagnostics — a young, partly contradictory field of research whose findings need careful framing.

Two messages run through all the chapters. First: none of these conditions can be cured at the root; the focus is on avoiding overexertion. Second: the state of knowledge is incomplete and in active development. This knowledge base therefore strives to be honest about what is established, what is plausible and what remains open — and so provides the basis for using mypacing in an informed and realistic way.

What this means for pacing & mypacing

One clear practical consequence follows from the whole state of knowledge: the most effective known way of dealing with PEM is to avoid it. Pacing means dosing activity so that your individual exertion limit is, as far as possible, not exceeded — not slowly "training yourself up". mypacing supports exactly this energy management, but it does not replace medical care and is not a medical device.

Heart rate as a guide. Many affected people use an individual upper heart-rate limit as a workable approximation, to stay in the "aerobic" range and thereby have fewer crashes. Such limits (often derived from simple rules of thumb) are aids to orientation, not validated medical thresholds. They do not replace listening to early warning signs and should ideally be accompanied by a doctor — especially because in POTS/dysautonomia heart rate alone (e.g. the orthostatic rise) can give a distorted picture.

Recognising and respecting PEM. Because the worsening often only sets in after 24–48 hours and can last for days to weeks, the link between activity and crash is not always immediately visible. Symptom and activity logs help you to find your own limit ("energy budget") and to stay below it.

Keeping triggers and environment in mind. Crashes do not arise only from physical effort. Cognitive load (screen time, conversations), emotional stress, orthostasis (long standing), lack of sleep, infections, pain, as well as sensory stimuli (light, noise) count as possible, partly modifiable PEM triggers. In POTS, simple measures can make everyday life easier: enough fluids and salt (after discussing with a doctor), compression, standing up slowly, avoiding heat. These ease circulatory symptoms but do not replace pacing.

What pacing is not. Pacing is not a cure and not a guarantee against crashes — it lowers their frequency and severity and protects against worsening from overexertion. Medications (chapters 9–10) act symptomatically, mostly off-label, and do not replace energy management.

Basic stance. mypacing provides structure, data and reminders for self-management. Decisions about limits, medication and exertion are made by the affected person together with their treatment team — not by the app.

Limits & open questions

This knowledge base describes a field in active development, and being honest about uncertainties is part of what it stands for.

Causes unclear. For Long COVID, ME/CFS and POTS there is no single, proven cause. The mechanisms discussed (viral persistence, immune dysregulation, autoimmunity, endothelial/mitochondrial disturbances) are plausible and in part well evidenced, but none is established as the sole explanation.

No biomarkers, clinical diagnosis. There is no routinely available, validated diagnostic test. Diagnoses rest on symptom criteria plus exclusion of other causes — which carries the risk of wrong and late diagnoses and makes it harder to tell overlapping pictures apart.

Thin medication evidence. The available studies, especially for POTS, are mostly small (often 11–54 people), short, cross-over in design and rarely carried out specifically in people with Long COVID or ME/CFS. No substance is approved for POTS in Germany; use is off-label. Supplements too lack proof of efficacy; none of it is curative.

Explicit warning about GET. Activating, escalating exercise therapy (graded exercise therapy, GET) is explicitly not recommended as a cure by the NICE guideline NG206 and can lead to worsening in PEM. "Push through" approaches are risky.

Be wary of promises of a cure. There is currently no cure. Offers that promise quick or complete recovery, "reprogramming" of the nervous system or expensive miracle cures should be judged critically — especially when they present pacing as unnecessary or push towards increasing exertion.

Open research questions. Subtyping, reliable exertion limits (including for heart-rate-based pacing), long-term courses, prognosis and causal therapies all remain unresolved. Recommendations may change with new evidence. This knowledge base is a snapshot and does not replace individual medical advice.

The chapters in detail

Sources

1. AWMF S1 guideline "Long/Post-COVID" (020-027), lead DGP, as of 08/2025 — register.awmf.org/de/leitlinien/detail/020-027
2. NICE Guideline NG206 "Myalgic encephalomyelitis/chronic fatigue syndrome: diagnosis and management" (2021) — nice.org.uk/guidance/ng206
3. Deutsche Gesellschaft für ME/CFS e.V. – "ME/CFS-Versorgungswüste" — mecfs.de/versorgungswueste
4. Charité Fatigue Centrum (CFC), Charité – Universitätsmedizin Berlin — cfc.charite.de
5. Münchner Chronische Fatigue Centrum (MCFC), TU München/Klinikum rechts der Isar — mcfc.mri.tum.de
6. Fatigatio e.V. – Bundesverband ME/CFS — fatigatio.de
7. Long COVID Deutschland — longcoviddeutschland.org
8. #MEAction – Pacing & Management Guides — meaction.net/pacing-and-management-guides
9. REHADAT-Wissen: Long COVID (disability, GdB, participation) — rehadat-wissen.de/ausgaben/12-long-covid
10. Long COVID-Plattform: Sozialgericht Speyer recognises GdB 50 for post-COVID syndrome — long-covid-plattform.de
11. Deutsche Rentenversicherung – reduced-earning-capacity pension — deutsche-rentenversicherung.de
12. ZEFQ (2024): experiences of affected people with inpatient rehabilitation in Long/Post-COVID — zefq-journal.com … S1865-9217(24)00092-8
13. PoTSDys e.V. – "PoTS und andere Dysautonomien e.V.", Bochum — pots-dysautonomia.net
14. Royal College of Anaesthetists – "ME/CFS and anaesthesia" (2024) — rcoa.ac.uk/.../me-cfs-anaesthesia
15. Swiss Society for ME & CFS (SGME) – patient materials, incl. emergency anaesthesia card — sgme.ch/infomaterial