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Long COVID / ME/CFS and Brain Fog

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Quick answer

Long COVID and ME/CFS can affect attention, memory and thinking speed. If physical or mental activity makes several symptoms worse later, tell your clinician about possible post-exertional malaise (PEM). Not everyone with Long COVID has PEM.

Evidence consensus

High - NICE NG188/NG206

NICE NG188 Long COVID (updated Jan 2024); NICE NG206 ME/CFS (2021, surveillance 2025)

Investigating: I think I have Long COVID or ME/CFS

Check what changed after the illness

Compare your daily abilities before and after the infection. Record symptoms during activity and any worsening later. These details help a clinician assess Long COVID, ME/CFS and other possible causes.

Quick Answer

What is usually happening here?

Long COVID and ME/CFS can cause trouble with attention, memory and thinking speed. Some people with Long COVID also have post-exertional malaise: symptoms worsen after physical or mental activity, often 12–48 hours later. PEM is required for an ME/CFS diagnosis, but not everyone with Long COVID has it.

PEM screen

Screen for symptoms after activity

Five DePaul Symptom Questionnaire items covering the past six months. Use the answers to discuss possible PEM with a clinician.

Symptom screening

Post-Exertional Malaise (PEM) Screen

These five DePaul Symptom Questionnaire items ask about symptoms after activity. They are the first step in assessing post-exertional malaise (PEM), not a diagnosis of PEM, ME/CFS or Long COVID.

Think about the past six months. Rate how severe each symptom has been and how often it has happened. If you have been ill for less than six months, tell your clinician; this questionnaire cannot cover its full recall period.

1. Dead, heavy feeling after starting to exercise

Severity

Frequency

2. Next-day soreness or fatigue after non-strenuous, everyday activities

Severity

Frequency

3. Mentally tired after the slightest effort

Severity

Frequency

4. Minimum exercise makes you physically tired

Severity

Frequency

5. Physically drained or sick after mild activity

Severity

Frequency

Cotler J, Holtzman C, Dudun C, Jason LA. Diagnostics. 2018;8(3):66. PMID 30208578.Read the questionnaire and scoring rules. Activity advice follows CDC guidance on Long COVID and PEM.

Clinical Evidence

The research at a glance

PEM changes the plan

If physical or mental activity causes delayed symptom flares, adapt activity and rest to your current limits. Tell your clinician about the delay so it is considered in testing and rehabilitation.

NICE NG188 Long COVID; NICE NG206 ME/CFS

Brain Imaging

Finding: A 2022 UK Biobank study found average imaging changes after COVID in adults aged 51–81. It doesn't show visible damage in every person with brain fog.

Douaud et al., Nature 2022. DOI 10.1038/s41586-022-04569-5

Cognitive Scores

Finding: A large 2024 community study found lower average cognitive scores in people with unresolved symptoms. Group differences do not measure an individual’s lost IQ.

Hampshire et al., NEJM 2024. PMID 38416429

Activity Guidance

Finding: NICE NG206 advises against fixed incremental exercise programs for ME/CFS and recommends individualized energy management.

NICE NG206, recommendations 1.11.2–1.11.14

Urgent Help

When to seek urgent medical attention

Get urgent care for a sudden severe headache unlike any before, new focal neurological symptoms (vision loss, one-sided weakness, trouble speaking), chest pain, high fever with confusion, or thinking that gets worse fast over days. These may mean stroke, encephalitis or another emergency, not typical post-viral illness.

Quick Win

One thing to do next

Write down one task that became harder after the illness, what happens when you try it, and how you feel later that day and the next. The activity plan and PEM screen below can help you prepare for an appointment.

CDC Long COVID clinical guidance; Cotler et al., Diagnostics 2018, PMID 30208578

Support Now

Immediate support actions

Body

Break up tasks that repeatedly cause delayed symptom flares and plan rest before and afterward. Use the amount of activity you can manage without a flare as a starting point.

Food

Use simple foods you can prepare or ask someone to bring: soup, eggs on toast, canned fish, rice or a sandwich. Enough food matters more than an elaborate diet. Ask for help if poor appetite or gut symptoms are causing weight loss.

Water

Drink regularly according to your needs and medical advice. If you have confirmed POTS, ask whether extra fluid or salt fits your health. Extra salt or fluid can be unsafe with some heart, kidney or blood-pressure conditions.

Environment

Reduce light, noise and interruptions when they worsen symptoms. Keep the sleeping space comfortable and discuss persistent insomnia, snoring or daytime sleepiness. No fixed room temperature or screen rule treats Long COVID.

Connection

Ask for one specific kind of help, such as a meal, grocery delivery or a ride to an appointment. Explain that long calls or busy visits may worsen symptoms, and suggest a manageable way to stay in touch.

Ask

Record activities and symptoms briefly, including delayed flares. A wearable may add information, but no heart-rate formula guarantees that an activity is safe.

Avoid

If you have PEM, avoid fixed exercise increases that ignore symptoms. Ask for an individualized plan. Treatment for coexisting stress, anxiety or depression can help those problems without replacing physical assessment.

Recognition

What it often feels like

Thinking problems after COVID can include poor concentration, slow thinking, trouble finding words or mental exhaustion. Some people also have delayed symptom flares after activity.

What changed after the illness, and what happens during and after ordinary activities?

Sleep problems, symptoms while upright and medicine effects may need assessment alongside the post-COVID symptoms.

  • Timing

    A normal errand or mental push can wipe me out at the time and later too.

  • Helped

    Rest helps a little, but it doesn't bring me back to my old baseline.

  • Trigger

    All of this started after a viral illness and never really went away.

  • Symptom

    When I crash, it's more than fatigue. My body, brain, and sensory tolerance all drop together.

  • Harmed

    Pushing through usually costs me later, even if I look fine while I am doing it.

Clinical Fit

How this cause is evaluated

History and symptoms to assess

For ME/CFS, assess whether physical or mental effort causes disproportionate symptom worsening, often delayed 12–48 hours. PEM is not required in every person with Long COVID.

For Long COVID, assess symptoms following SARS-CoV-2 infection. ME/CFS can follow other infections or have no clear infectious onset.

Symptoms to discuss

Waking unrefreshed regardless of sleep duration

Word-finding difficulty, memory problems, confusion

Symptoms worse standing, better lying down

Unpredictable good and bad days

Delayed crashes that last days after overdoing it

Reasons to assess further

Some activity is tolerated or helpful: this does not by itself exclude Long COVID or ME/CFS.

Sudden weakness, new trouble speaking or other focal neurological symptoms require urgent assessment.

Symptoms that predate COVID need assessment in their own right; a new post-COVID problem may coexist.

Differential

How to tell this apart from nearby causes

Do ordinary physical or mental activities repeatedly leave several symptoms worse later?

If yes: Discuss PEM as well as mood. Depression and a post-infectious illness can coexist.

If no: A lack of delayed flares doesn't prove depression or rule out Long COVID. Review mood, sleep and the symptom timeline.

Do you snore loudly, wake gasping or have witnessed breathing pauses during sleep?

If yes: Ask about sleep apnea assessment. Sleep apnea can occur alongside Long COVID.

If no: These symptoms are clues, not a rule-out test. Persistent unrefreshing sleep or daytime sleepiness still deserves review.

Have you also developed cold intolerance, constipation or an unexplained weight change?

If yes: Ask whether thyroid testing is appropriate.

If no: A thyroid disorder can occur without all these symptoms. Review whether testing is indicated rather than choosing a cause from this question.

Do episodes occur with thirst, frequent urination, shakiness or a clear relation to meals?

If yes: Describe the episodes and ask whether glucose testing would help.

If no: This answer does not establish a post-viral cause. Consider the wider history and any indicated tests.

Key Takeaways

Long COVID, ME/CFS and brain fog in brief

  • Long COVID and ME/CFS can both cause thinking problems, but they are not interchangeable diagnoses. PEM is required for ME/CFS; it occurs in some, not all, people with Long COVID.
  • When activity causes delayed symptom flares, plan rest and adjust activity to your current limits. NICE advises against fixed increases in exercise for ME/CFS.
  • No single laboratory test confirms either illness. Tests can identify other causes and treatable problems such as anemia, thyroid disease, sleep apnea or POTS.
  • Recovery varies. Some people improve, while others remain substantially limited for years. Continuing symptoms do not mean that someone has failed at pacing.
  • Bring a record of symptoms, daily function and delayed effects of activity. A normal routine test or a brief good performance does not explain everything a person can sustain at home.
  • Treatments should have a specific purpose and a way to judge benefit and harm. Low-dose naltrexone and several other proposed medicines remain off-label and uncertain; they should not be treated as established cures.
Patient Language

How people describe it

People describe several kinds of thinking problems. One person may lose words during a conversation; another can think clearly for a few minutes but becomes exhausted by reading or a meeting. Some also feel worse later that day or the next.

my brain never came back after covidpost-exertional crashlong hauler brain fogi read a paragraph and nothing sticksmy batteries drain fast and refill slowly

  • Some people report delayed flares after physical, mental or social activity. This is important to assess, but not everyone with Long COVID has PEM.

  • Some can think clearly for a short time but cannot sustain reading, work or conversation. Others struggle with memory or word finding from the start.

  • Describe the task, how long you can manage it and what happens afterward, rather than relying only on the phrase brain fog.

Common Confusions

How this differs from conditions it gets mistaken for

Sleep Apnea

Both can involve poor concentration, unrefreshing sleep and daytime fatigue. Snoring, breathing pauses and sleepiness suggest checking for apnea. Delayed flares after activity suggest assessing PEM. Both conditions can coexist.

Key question: Do you have snoring or breathing pauses, delayed flares after activity, or both?

Open comparison

Sleep

Poor sleep can worsen thinking whether or not Long COVID is present. Improvement after better sleep does not rule out Long COVID, and persistent symptoms do not identify one cause.

Key question: Which symptoms change when sleep improves, and which remain?

Open comparison

POTS

POTS and other causes of symptoms while upright can occur alongside Long COVID. Dizziness, palpitations or worse thinking while standing need assessment.

Key question: Do standing or sitting upright worsen symptoms, and does lying down help?

Open comparison

EBV

EBV can cause an acute illness and remains in the body afterward. Evidence of past EBV infection is common and doesn't show that EBV is causing current Long COVID symptoms.

Key question: Is there evidence of a current EBV-related illness, or only antibodies from a past infection?

Open comparison

Hypoperfusion

Reduced brain blood flow is being studied in some patients, especially during upright testing. It is a possible contributor, not a separate diagnosis that can be chosen from a symptom list.

Key question: Are symptoms related to being upright, and would supervised circulation testing change care?

Open comparison

Medication Side Effects

Medicines used for sleep, allergies, pain or heart rate can add sleepiness or thinking problems. Medicine effects and post-viral symptoms may occur together.

Key question: What changed after each medicine or dose change, and what was already happening before it?

Open comparison

Burnout

Work stress, poor sleep and Long COVID can all reduce concentration. Delayed flares after ordinary activity warrant assessment for PEM, but improvement on vacation or a difficult workday cannot by itself separate the causes.

Key question: What happens after small amounts of activity on workdays and days off, and when did the change begin?

Open comparison

Controversies

Where the evidence is contested

It's just anxiety or depression

Anxiety and depression can occur alongside Long COVID and deserve treatment. They do not explain every case of persistent cognitive symptoms. Studies have found group differences in cognitive performance and brain imaging after COVID, but neither finding identifies the cause of one person’s symptoms. Assess physical symptoms, sleep and mental health together rather than using one diagnosis to dismiss the others.

Hampshire et al., NEJM 2024; Douaud et al., Nature 2022

Graded Exercise Therapy (GET) will help you recover

NICE advises against exercise programs for ME/CFS that increase activity by fixed amounts regardless of symptoms. Physical and mental effort can trigger PEM, sometimes after a delay. Activity plans need to account for this response and change during a flare or relapse. Pacing aims to reduce worsening; it does not promise recovery.

NICE NG206 2021 (GET removal); ME/CFS Clinician Coalition

Your tests are normal, so nothing is wrong

There is no single laboratory test for Long COVID or ME/CFS. Routine tests can help find other conditions, and normal results do not rule out either illness. Symptoms may justify a sleep assessment, a medication review or measurements while lying and standing. Research tests of immune proteins, microclots or gut bacteria are not established diagnostic panels.

CDC Long COVID Clinical Guidance; NICE NG188; NICE NG206

You should be better by now

Long COVID can last months or years, with improvement, relapse or continuing symptoms. There is no deadline after which persistent illness means someone has failed to recover properly. Support should address current needs: daily activities, work or school, sleep, symptoms while upright and access to care. Follow-up matters even when the recovery timeline is uncertain.

Institute of Medicine (US) Committee on the Diagnostic Criteria for ME/CFS 2015 report (NCBI NBK274235); NICE NG206 ME/CFS 2021; NICE NG188 Long COVID 2024

There is a single clinical diagnostic test for Long COVID

No single test can diagnose Long COVID. A clinician considers the illness history, symptoms and other possible causes. The 2024 RECOVER-Adult Research Index, developed using 13,647 participants, classifies people for research; it is not a clinical diagnostic test. A positive test from the original infection is not required for a clinical diagnosis.

RECOVER-Adult 2024 Long COVID Research Index, JAMA 2024 (PMID 39693079); WHO Post COVID-19 condition clinical case definition 2021; NICE NG188 Long COVID 2024

There's no treatment - just wait it out

There is no established treatment that cures Long COVID, but there are symptoms and related conditions worth treating. Examples include sleep apnea, migraine and orthostatic intolerance. Pacing may reduce PEM. Small observational studies suggest possible benefit from low-dose naltrexone, but controlled evidence is still lacking. Rehabilitation should match the person’s difficulties and avoid worsening symptoms.

CDC Long COVID Clinical Guidance; NICE NG206; Byambasuren et al., BMJ Open 2026 (PMID 42463201)

Long COVID is the same as ME/CFS

Some people with Long COVID meet the criteria for ME/CFS, but many do not. PEM is a required part of ME/CFS and occurs in a subset of people with Long COVID. Long COVID can also involve lung, heart and other problems. Assessing the actual symptoms matters more than assuming that one label describes every person.

Komaroff & Lipkin, Lancet 2023; Davis et al., Nat Rev Microbiol 2023

Compare

Long COVID Brain Fog vs Depression

Similar symptoms can have more than one cause. These clues guide assessment; none diagnoses or excludes Long COVID by itself.

vs Depression

Depression can affect concentration, energy, sleep and interest in activities. A delayed flare of several symptoms after small amounts of physical or mental activity raises a separate question about PEM. Neither motivation nor a response to exercise can diagnose the cause. Depression and Long COVID can coexist and each deserves care.

vs Sleep Apnea

Snoring, witnessed breathing pauses and daytime sleepiness suggest checking for sleep apnea. Long COVID can include delayed worsening after activity and symptoms while standing. Timing alone can't separate them, and both can occur together. Treating sleep apnea may help even when some Long COVID symptoms remain.

vs Thyroid

Thyroid disease can cause fatigue and slow thinking, sometimes with constipation, cold intolerance or weight changes. Blood tests can check thyroid function. A thyroid problem and Long COVID can occur together.

Timing

When brain fog tends to show up

Sketch of when brain fog usually worsens, not measured data.

Worse after exertion

With PEM, symptoms often worsen 12–48 hours after effort, though they can start sooner. Other Long COVID symptoms can occur without that delay.

Unpredictable episodes

Persistent through the day

Worse in the morning

Evidence

What people often miss

Research is beginning to explain some post-COVID symptoms, but it has not found one cause or treatment for everyone. These studies show what is known, what remains uncertain and which findings may be useful at an appointment.

Brain-scan changes have been found after COVID. In the UK Biobank study, 785 adults aged 51–81 had scans before and after the pandemic; 401 had COVID between scans and 384 were controls. The COVID group had greater average loss of gray-matter thickness in some regions and greater reduction in total brain size. Findings remained after hospitalized cases were excluded. This was a group comparison, not proof that every person with brain fog has visible brain damage or that the changes are permanent.

Douaud et al., Nature 2022

[DOI]

Two-day cardiopulmonary exercise testing (CPET) measures how the body responds to a second exercise test 24 hours after the first. Some ME/CFS studies find lower oxygen use or work capacity on day two, including at the ventilatory threshold. The size of the change varies; there is no universal 30% drop that diagnoses PEM. Testing can provoke a substantial symptom flare. It is not needed for routine diagnosis and should be considered only for a clear purpose with informed consent and specialist supervision.

Stevens S et al., Front Pediatr 2018;6:242. PMID 30234078

A 2024 NIH study examined 17 people with post-infectious ME/CFS and 21 healthy volunteers using neurological, immune, autonomic and exercise tests. On a task offering choices of effort for reward, the ME/CFS group chose fewer difficult tasks. The authors proposed a role for brain circuits involved in effort. That interpretation has been disputed, including in published correspondence. The small, selected study doesn't show that unwillingness to try causes ME/CFS.

Walitt B et al., Nat Commun 2024 (PMID 38383456)

Joint hypermobility, POTS, ME/CFS and Long COVID can overlap. A 2024 perspective summarized selected studies reporting hypermobility in about 30% of Long COVID patients, 49% of ME/CFS patients and 57% of POTS patients. These are different study populations, not estimates that apply to every clinic. Mast-cell and connective-tissue mechanisms remain proposed explanations. Recurrent joint instability, pain, dizziness while standing or allergy-like episodes can guide an assessment for a coexisting condition.

Ganesh R et al., Front Neurol 2024 (PMID 39301475)

Sleep apnea can be a treatable contributor after COVID. A study of 34 patients referred with new fatigue and sleepiness found obstructive sleep apnea in 35%. Six patients who continued treatment reported that their daytime symptoms resolved. This small, selected group does not show how common apnea is in everyone with Long COVID. Snoring, witnessed breathing pauses or persistent daytime sleepiness are reasons to ask about sleep testing; a Long COVID diagnosis does not replace that assessment.

Menzler K et al., Eur J Neurol 2024 (PMID 37987095)

ME/CFS diagnostic criteria share important symptoms but are not identical. NICE, the 2015 IOM/NAM criteria, the Canadian Consensus Criteria and the International Consensus Criteria all include post-exertional symptoms. Their required symptom combinations, duration and severity differ. For example, the IOM criteria require more than six months of reduced function, PEM, unrefreshing sleep, and either thinking problems or orthostatic intolerance. Ask which criteria the clinician is using and which requirements you meet. No questionnaire score alone establishes the diagnosis.

Carruthers BM et al., J Intern Med 2011 (PMID 21777306) - ICC; Carruthers BM et al., J Chronic Fatigue Syndr 2003;11(1):7-115 - CCC; IOM/NAM 2015 Beyond ME/CFS report (NCBI Bookshelf NBK284898); NICE NG206 2021

A large UK study found lower average cognitive scores after COVID. Of 112,964 adults completing online testing, those with unresolved persistent symptoms had an average deficit equivalent to about six IQ points compared with the reference group; smaller differences, roughly three points, were seen after symptoms had resolved. Larger differences were seen after intensive care. These are comparisons between groups, not before-and-after IQ losses measured in each person. They cannot tell you how many points you personally lost or whether you will recover.

Hampshire A et al., NEJM 2024 (PMID 38416429)

[DOI]

A 2025 UK Biobank study followed adults aged 50 and older for more than two years. New dementia diagnoses, especially vascular dementia, were more frequent after COVID than in uninfected controls. The risk was not higher than after other respiratory illnesses. This observational result cannot predict an individual outcome, and brain fog is not itself a dementia diagnosis. A continuing loss of everyday skills needs assessment rather than an assumption that it is ordinary Long COVID.

Shan D et al., npj Dementia 2025;1:28

[DOI]

EBV reactivation is one research question, not an explanation for every case of Long COVID. In a small 2021 study, 20 of 30 participants with persistent symptoms had selected EBV antibody markers, compared with 2 of 20 controls: 66.7% versus 10%. The study found an association. It did not establish that EBV caused the symptoms or test whether antivirals improved them.

Gold et al., Pathogens 2021

[DOI]

Researchers have studied how cells make and use energy in ME/CFS. A 2009 study of 71 patients and 53 controls found an association between illness severity and measures of ATP production in blood cells. ATP is a molecule cells use for energy. The study proposed a mechanism; it did not establish that a four-day ATP replacement process explains the timing of every PEM episode, or validate a treatment for Long COVID.

Myhill et al., Int J Clin Exp Med 2009

Mental activity can trigger PEM as well as physical activity. Reading, work, conversation and screens may need to be included in activity planning. Resting physically while doing demanding mental work may therefore not provide the break you need. Which activities are tiring, and how much you can tolerate, varies between people.

NICE NG206 ME/CFS guideline 2021

Dizziness, a racing heart or worse thinking while upright are reasons to ask for standing measurements. A clinician can record heart rate, blood pressure and symptoms while lying down and standing, sometimes for up to ten minutes. POTS requires more than one high pulse reading: symptoms, duration, blood-pressure behavior and other causes matter. Do not stand through faintness or severe symptoms to complete a home test.

Blitshteyn & Whitelaw, Immunol Res 2021

[DOI]

The DePaul Symptom Questionnaire records symptoms used in ME/CFS research and assessment. The five-item PEM screen on this page asks about the past six months. At least one symptom rated moderate or worse and occurring at least half the time meets its first-step threshold. A clinician must then assess the history, duration and other possible causes.

Cotler J et al., Diagnostics 2018;8(3):66

The Daily activity plan lists what you intend to do. It does not convert an energy rating into a safe activity allowance. Keep a brief separate record of what you actually did and whether symptoms worsened later. Comparing manageable days with flare days may help you and your clinician adjust the plan.

NICE NG188 Long COVID guideline; NICE NG206 ME/CFS guideline

NICE recommends a validated screening tool when someone reports new cognitive symptoms after COVID. A clinician may use a tool such as the MoCA, but a brief result does not capture every problem with mental endurance or daily tasks. Bring examples of what goes wrong, how long you can concentrate and what happens after effort, even if a screening score is normal.

NICE NG188 Long COVID guideline 2024

EBV antibody results need clinical interpretation. Most adults have evidence of past EBV infection, and some antibodies can remain positive without explaining current symptoms. A small association study is not a reason for everyone with Long COVID to request an EBV panel or start antivirals. Ask what question testing would answer and how the result would change care.

CDC: Laboratory testing for Epstein-Barr virus; Gold et al., Pathogens 2021

[DOI]

Describe symptoms during standing, not just the pulse reading. Note whether dizziness, blurred vision, palpitations or thinking problems improve when you sit or lie down. The clinician can choose an active stand, NASA Lean Test or tilt-table test and check other causes such as dehydration, anemia and medicine effects.

Blitshteyn & Whitelaw, Immunol Res 2021

[DOI]

In 2021, NICE advised against fixed increases in exercise for ME/CFS, including the approach it calls graded exercise therapy. That does not forbid every form of movement or rehabilitation. A person who chooses an activity program should have an individualized plan that can be reduced or adjusted when symptoms worsen, with specialist support where available.

NICE NG206 2021

Repeatedly exceeding your current limits can worsen symptoms and lead to prolonged setbacks when you have PEM. Plan necessary activities with breaks and practical help, and review a plan that keeps causing flares. Pacing aims to reduce those flares; it cannot guarantee that symptoms will stop or that the illness will recover.

ME/CFS Clinician Coalition clinical management guidance

Long COVID and ME/CFS can last for years, but improvement is still possible. Address treatable symptoms, adjust daily tasks and protect time for rest when activity causes PEM. Do not use a better day as proof that you can safely return to your old schedule. Changes in activity should reflect what remains manageable afterward.

NICE NG188 Long COVID guideline; NICE NG206 ME/CFS guideline

If symptoms are new, start with the assessment, PEM screen and appointment preparation. If you already know the diagnosis and pacing basics, the What helps guide compares practical support, symptom treatments and current trial results. Neither illness duration nor familiarity with research determines which treatment will work for you.

Researchers are investigating blood flow, immune changes and cell energy, but these findings do not yet form one proven explanation. In a 2020 tilt-table study, brain blood flow fell by an average of 26% in 429 ME/CFS patients compared with 7% in 44 controls; 90% of the patient group crossed the study’s abnormal threshold. These were selected patients, and the result does not diagnose an individual without testing. Separately, Greene and colleagues found blood-brain barrier differences in a small Long COVID study. Receptor autoantibodies and impaired energy production remain mechanisms to investigate, not proof that everyone needs immune treatment.

Wirth K, Scheibenbogen C, Autoimmun Rev 2020 (PMID 32247028); van Campen CLMC, Verheugt FWA, Rowe PC, Visser FC, Clin Neurophysiol Pract 2020 (PMID 32140630); Greene C et al., Nat Neurosci 2024 (PMID 38388736)

Small-fiber neuropathy can cause burning pain, tingling, altered sweating and other autonomic symptoms. In a selected series of 17 people referred for prolonged Long COVID, 59% had at least one test confirming neuropathy, and 63% of the skin biopsies were abnormal. Those figures do not show its prevalence in all Long COVID. An examination can guide whether nerve testing or a skin biopsy is useful. Reports of improvement with immune treatment are not enough to make IVIG routine treatment for Long COVID or unexplained brain fog.

Oaklander AL, Mills AJ, Kelley M, Toran LS, Smith B, Dalakas MC, Nath A, Neurol Neuroimmunol Neuroinflamm 2022 (PMID 35232750)

The Patient-Led Research Collaborative documented symptoms that were easy to miss in routine appointments. Its peer-reviewed 2021 survey included 3,762 people from 56 countries and asked about 203 symptoms across 10 organ systems. More than 85% reported relapses; fatigue, post-exertional malaise and cognitive problems were prominent at six months. Participants came mainly through online support groups, so this was not a population prevalence survey. Its lasting contribution was to document the range, duration and daily impact of symptoms, including trouble working, in patients’ own reports.

Davis HE, Assaf GS, McCorkell L, Wei H, Low RJ, Re'em Y, Redfield S, Austin JP, Akrami A. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact. eClinicalMedicine 2021;38:101019 (PMID 34308300)

[DOI]

A New York study examined health records for 62,339 patients with COVID-19. During days 31–180 after infection, hospitalized Black patients had about twice the adjusted odds of a diabetes diagnosis and 1.5 times the odds of a headache diagnosis compared with hospitalized white patients. Hospitalized Hispanic patients also had higher odds of headaches. These are differences in recorded diagnoses. They don't prove one biological or social cause. The authors called for research into the reasons. At an appointment, ask how your symptoms are being assessed and what follow-up is planned. A normal routine test does not explain away continuing symptoms.

Khullar D et al., Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program, J Gen Intern Med 2023 (PMID 36795327, n=62,339)

In an Italian prospective study of 377 patients, being female was associated with Long COVID after researchers accounted for other measured factors. A 2022 review also found higher odds among women. These studies support a difference in risk; they do not show that a fixed 65–80% of all people with Long COVID are women, or explain every individual’s illness. Immune and hormonal explanations remain under study. Sex should not determine whether someone’s post-COVID symptoms receive a careful assessment.

Bai F et al., Clin Microbiol Infect 2022 (PMID 34763058, prospective cohort n=377); Sylvester SV et al., Curr Med Res Opin 2022 (PMID 35726132, systematic review)

Researchers have described persistent symptoms beginning after COVID-19 vaccination, sometimes called post-acute COVID-19 vaccination syndrome (PACVS). A 2024 registry study included 191 selected patients and reported fatigue, nerve symptoms, cardiovascular symptoms and cognitive problems. More than 80% had elevated IL-6 and IL-8 or low free T3; these findings were not tied to specific symptoms and are not a validated diagnostic panel. The authors assigned 131 of 191 participants to an ME/CFS-like group using their study method. This registry can't show how often the syndrome happens among vaccinated people. A separate NIH-led report described 23 patients with new nerve symptoms within a month of vaccination. It remains a preprint. Seven of 12 steroid-treated patients had complete or near-complete improvement after two weeks, and three later received IVIG with reported improvement. Treatment wasn't randomized, so these observations don't prove it works or justify self-treatment. Record the timing, symptoms and any infections for a medical assessment; timing alone can't prove the cause.

Safavi F et al., Neuropathic symptoms with SARS-CoV-2 vaccination, medRxiv preprint 2022 (PMID 35611338; not peer reviewed); Mundorf AK et al., Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome, Vaccines 2024 (PMID 39066428). Further reading: Platschek B and Boege F, Vaccines 2024 (PMID 39772040); Scholkmann F and May CA, Pathology Research and Practice 2023 (PMID 37192595).

History

Key Research Milestones in Long COVID / ME/CFS and Brain Fog

Research has identified group differences and tested several treatments. These milestones also show why a proposed mechanism is not yet a diagnostic test or a proven treatment.

2009

Myhill and colleagues study cell energy in CFS

A study of 71 patients and 53 controls linked measures of ATP production in blood cells with illness severity. It proposed a mitochondrial explanation but did not establish the cause or timing of PEM in every patient.

2015

IOM publishes ME/CFS diagnostic criteria

The criteria include a substantial loss of function lasting more than six months, fatigue, PEM, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance.

2021

NICE changes its ME/CFS activity guidance

The guideline advises against programs with fixed increases in exercise. Energy management and any chosen activity program should be individualized and adjusted when symptoms change.

2021

Gold and colleagues examine EBV markers

A small study found EBV reactivation markers more often in participants with Long COVID. It did not show that EBV caused their symptoms or that antiviral treatment would help.

2022

Douaud and colleagues compare brain scans before and after COVID

The UK Biobank study found average imaging changes in people who had COVID compared with controls. It did not show that every infected person developed brain damage or explain every case of brain fog.

2024

Hampshire and colleagues measure cognition after COVID

In a large community study, people with unresolved symptoms had lower average cognitive scores. These between-group differences are not an individual measurement of lost IQ.

2024

Greene and colleagues investigate the blood-brain barrier

A small study found differences in the blood-brain barrier in participants with Long COVID brain fog. This supports further vascular and immune research; it does not establish a single cause or routine diagnostic scan.

2025

RECOVER-NEURO tests three cognitive treatments

RECOVER-NEURO trial (328 participants, JAMA Neurology): cognitive rehab, brain training (BrainHQ), and brain stimulation (tDCS) didn't outperform active control for long COVID brain fog. All groups improved over time, but no intervention was superior.

2025

Researchers test a five-item brain fog questionnaire

Researchers tested the five-item Brief Brain Fog Scale in an online survey of 844 people: 686 reporting post-COVID brain fog and 158 controls. It measures reported symptoms.

2025

A review proposes a role for brain waste clearance

A 2025 review proposed that impaired glymphatic clearance, the removal of waste products from the brain, might contribute to ME/CFS. It called for investigation rather than establishing this mechanism in patients.

Doctor Prep

How to bring this to a clinician

Opening script

Since [infection and date], I have had [thinking problems] and can no longer manage [specific tasks] as before. I want to discuss Long COVID, whether I meet ME/CFS criteria, and other treatable causes. I have noticed [describe any worsening after activity, its timing and duration, or say that you have not noticed this].

Tests to discuss

  • CBC and CMP when symptoms or history warrant blood counts and metabolic checks
  • TSH, B12 and ferritin when symptoms or history suggest a thyroid problem or deficiency
  • HbA1c when blood sugar assessment is indicated
  • Lying and standing vital signs or an active stand test for symptoms while upright
  • Sleep study when symptoms suggest sleep apnea or another sleep disorder
  • Cognitive assessment to document thinking difficulties
  • Medication review for possible effects on thinking, sleep or fatigue

Points to raise

  • Long COVID can cause symptoms in several body systems. Symptoms can stay, go away and return, or begin after the first illness seemed to end. A positive COVID test is helpful but is not required by CDC guidance.
  • Post-exertional malaise means that activity causes an unusually large worsening of symptoms. Walking, showering, reading, talking, concentrating, stress, or social time can bring it on. Symptoms often worsen 12–48 hours later, but can begin sooner and last for days or longer.
  • Under the US Institute of Medicine criteria, ME/CFS requires a major drop in previous activity for more than six months, post-exertional malaise, and unrefreshing sleep. The person must also have thinking problems or symptoms that become worse while upright.
  • NICE uses a three-month symptom duration for an ME/CFS diagnosis in the UK. Long COVID and ME/CFS overlap, but a person with Long COVID does not automatically have ME/CFS.
  • No post-exertional malaise makes ME/CFS less likely. It does not rule out Long COVID, because not everyone with Long COVID has post-exertional malaise.
  • Anemia, thyroid disease, vitamin B12 deficiency, diabetes, sleep apnea, migraine, and medicine effects can cause similar symptoms. Depression, anxiety, heart or lung disease, and an abnormal response to standing may also need checking.

What to bring

  • Bring a dated list of suspected or confirmed COVID infections and other infections. Include positive tests if you have them, but do not worry if testing was unavailable or negative.
  • Write what you could do before the illness and what you can do now. Use real examples from work, school, reading, driving, shopping, showering, cooking, childcare, exercise, and social time.
  • If you can, keep brief notes on demanding activities and how you feel later that day and over the next two days. Bring the notes you have; do not delay an appointment or cause a crash to complete a diary.
  • List the symptoms that become worse together, such as brain fog, heavy fatigue, pain, sore throat, headache, poor sleep, dizziness, racing heart, breathlessness, or sound and light sensitivity.
  • Bring prior blood tests, heart or lung tests, scans, sleep results, and visit notes from before and after the infection. Dates matter.
  • Bring every prescription, over-the-counter medicine, supplement, inhaler, stimulant, sleep aid, antihistamine, and pain medicine. Include timing and what changed after starting it.
  • If you already measure heart rate, blood pressure, oxygen, temperature, sleep, or steps, bring a short dated summary. Skip repeated testing or exercise done just to produce data.
  • Bring forms or a short list of the work, school, driving, mobility, or care tasks that now need an adjustment.

Screening tools

  • Long COVID is diagnosed from the infection and symptom history, examination, and tests chosen for the symptoms. CDC says a positive COVID test is not required and there is no laboratory test that can rule Long COVID in or out.
  • The US Institute of Medicine criteria check for more than six months of reduced function, post-exertional malaise, unrefreshing sleep, and either thinking problems or symptoms that become worse while upright.
  • NICE allows an ME/CFS diagnosis after three months when the required symptoms persist and another condition does not explain them. Ask which criteria the clinician is using.
  • A short activity and symptom diary can show whether several symptoms get worse after physical, mental, emotional, or social activity. Record ordinary life only and skip any planned exercise challenge.
  • Heart rate and blood pressure while lying and standing can identify an abnormal response to being upright. A clinician may use an active stand or tilt table test when the symptoms give a reason. A pulse number alone can't confirm the diagnosis; blood pressure, symptoms and medical history matter too.
  • A brief thinking test can record attention, memory, language, or processing problems. Describe everyday difficulties even if the test score is normal.
  • A sleep study can identify sleep apnea or another sleep disorder. Unrefreshing sleep can also occur in ME/CFS even when a sleep study does not find apnea.
Doctor Scripts

When concerns are dismissed

  • Treatment Not Working

    Activity makes my symptoms worse after [delay]. How will the plan account for possible PEM? I understand NICE advises against fixed increases in exercise for ME/CFS.

NICE NG206 2021; NICE NG188 2024; Institute of Medicine diagnostic criteria 2015

  • Test Results

    I understand normal tests do not rule out Long COVID. Could we document the effect on daily life and agree what needs assessment or treatment next?

NICE NG206 2021; NICE NG188 2024; Institute of Medicine diagnostic criteria 2015

  • Second Opinion

    I am open to assessing depression. Could we also assess my physical symptoms, thinking problems and any worsening after activity, rather than assume one diagnosis explains everything?

NICE NG206 2021; NICE NG188 2024; Institute of Medicine diagnostic criteria 2015

Escalation

When Should You See a Doctor for Long COVID Brain Fog?

Arrange an assessment when brain fog after COVID persists, worsens or interferes with daily life. Bring examples of what changed and any delayed symptoms after activity.

Symptoms affect everyday tasks

Ask for an assessment if concentration, memory or fatigue interferes with work, study, driving or self-care.

Your abilities are declining

Seek earlier review if you need increasing help or cannot manage food, fluids, medicines or basic care.

Another problem may be treatable

Mention snoring or breathing pauses, dizziness while standing, new headaches, medicine changes and other symptoms that may guide testing.

A new emergency symptom

Sudden weakness or speech trouble, a sudden severe headache, severe breathlessness or persistent chest pain needs urgent care.

FAQ

Questions that actually matter here

Is it this cause

How is Long COVID / ME/CFS brain fog different from sleep apnea?

Snoring, witnessed breathing pauses and daytime sleepiness suggest checking for sleep apnea. Long COVID can include delayed worsening after activity and symptoms while standing. Timing alone can't separate them, and both can occur together. Treating sleep apnea may help even when some Long COVID symptoms remain.

Clinical observation consistent with NICE NG206 ME/CFS 2021 and NICE NG188 Long COVID 2024. These timing differences come from clinical observation, not one study.

Can Long COVID / ME/CFS cause brain fog?

Yes. Both can affect attention, memory and thinking speed. They overlap but are different diagnoses. Some people with Long COVID meet ME/CFS criteria, which include post-exertional malaise, unrefreshing sleep and a lasting reduction in activity. Others have cognitive symptoms without PEM.

What does Long COVID / ME/CFS brain fog usually feel like?

You may lose words, forget instructions or need longer to follow a conversation. Some people can think clearly for a short time but become exhausted after reading or talking. Record both what is difficult and how long you can do it. If symptoms worsen later after activity, tell your clinician about that delay too.

Long COVID brain fog vs depression: how to tell

Depression can affect concentration, energy, sleep and interest in activities. A delayed flare of several symptoms after small amounts of physical or mental activity raises a separate question about PEM. Neither motivation nor a response to exercise can diagnose the cause. Depression and Long COVID can coexist and each deserves care.

How quickly can I tell whether this path is helping?

Compare symptoms and ordinary activities over time, including the day or two after demanding tasks. Look for fewer flares or a specific task you can manage more reliably. If a plan repeatedly worsens symptoms, ask for it to be adjusted rather than continuing to increase activity.

Does metformin or blood sugar overlap matter in Long COVID / ME/CFS brain fog?

Meal-related symptoms deserve assessment, but they do not by themselves prove a blood-sugar problem. Blood pressure changes after meals and diabetes are among the possibilities. Metformin studied during acute COVID to reduce later Long COVID risk is a different question from using it for established Long COVID. Do not start it for brain fog without a medical indication.

Testing

What tests should I discuss for Long COVID / ME/CFS brain fog?

No single test confirms Long COVID or ME/CFS. The history and examination guide checks for other causes and treatable problems. Depending on your symptoms, these may include blood counts, thyroid function, B12, iron, glucose, sleep testing or supervised heart-rate and blood-pressure measurements while standing. Cognitive testing can document difficulties but doesn't identify the cause by itself. Two-day exercise testing can provoke a prolonged flare and is not routine screening. Research tests of microclots, immune proteins or brain inflammation are not established diagnostic tests.

Treatment

Long COVID hit and my brain never recovered. Does anyone actually get better?

Some people improve or recover, while others remain limited for years. There is no reliable individual recovery deadline. Track changes in everyday function as well as symptoms: fewer crashes, longer manageable conversations or less help with self-care may matter. Pacing aims to reduce post-exertional flares; it does not guarantee recovery.

Clinical observation consistent with NICE NG206 ME/CFS 2021 and NICE NG188 Long COVID 2024. These timing differences come from clinical observation, not one study.

What should I try first if I think Long COVID / ME/CFS is involved?

Record when symptoms began, what you can do now compared with before the infection, and whether physical or mental activity makes symptoms worse later. The five-question PEM screen on this page can help organize part of that history. If activity causes delayed flares, reduce or break up those activities and plan rest while you arrange an assessment.

When to see a clinician

My doctor says Long COVID brain fog will resolve on its own. Should I trust that?

Improvement is possible, but no one can promise when your symptoms will resolve. Ask what supports that expectation in your case, what treatable problems have been checked, and when to review progress. A follow-up plan should include changes in daily function and what to do if symptoms worsen. Waiting for recovery should not mean going without symptom treatment or practical support.

NICE NG188: COVID-19 rapid guideline: managing the long-term effects of COVID-19

When should I bring Long COVID / ME/CFS brain fog to a clinician?

Arrange an assessment when brain fog persists, affects daily tasks or worsens after COVID. You do not need to finish a trial of pacing first. Ask sooner if you are losing the ability to work, study or care for yourself. Sudden one-sided weakness, new speech trouble, a sudden severe headache, severe breathlessness or persistent chest pain needs urgent care.

Track this cause

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Visit prep

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Last reviewed 2026-03-23 | Reviewed by Dr. Alexandru-Theodor Amarfei, M.D.

Related Articles

Long COVID and Brain Fog

Post-viral cognitive dysfunction and ME/CFS overlap.

Long COVID Symptoms Do Not Follow One Script

How researchers group Long COVID symptoms and why the problems you have should guide care.

Neuroinflammation and Brain Fog

What researchers know and are still investigating about inflammation and thinking problems.

Related Causes

Neuroinflammation

POTS

Sleep

Sleep Apnea

Gut

Histamine

Doctor Handout Visit-ready clinician handout

References

  1. Greene et al., Nat Neurosci, 2024 - Blood-brain barrier disruption in Long COVID
  2. NICE NG206 ME/CFS guideline (2021/2024)
  3. NICE NG188 Long COVID guideline (2024)
  4. Institute of Medicine (National Academy of Medicine), 2015 - diagnostic criteria for ME/CFS
  5. Davis HE et al., Nat Rev Microbiol, 2023 - Long COVID: major findings, mechanisms and recommendations
  6. NICE NG206 ME/CFS 2021; Davis et al., Nat Rev Microbiol 2023; Komaroff & Lipkin, Lancet 2023
  7. NICE NG206: ME/CFS diagnosis and management — Clinical guideline — Open source
  8. CDC: Clinical care of ME/CFS — Clinical guidance — Open source
  9. WHO: Clinical management of COVID-19 living guideline and post-COVID rehabilitation — International guidance — Open source
  10. Pulmonary rehabilitation in Long COVID: systematic review/meta-analysis — Systematic review and meta-analysis — Open source
  11. STIMULATE-ICP integrated care pathway trial — Phase 3 cluster-randomized trial — Open source
  12. CDC: Long COVID clinical guidance — Clinical guidance — Open source
  13. Diagnosis and management of POTS — Clinical review — Open source
  14. POTS after COVID-19: systematic review of interventions — Systematic review of reports — Open source
  15. Pyridostigmine physiology trial in ME/CFS — Randomized double-blind placebo-controlled physiology trial — Open source
  16. NICE NG188: managing the long-term effects of COVID-19 — Clinical guideline — Open source
  17. Interventions for long COVID: living systematic review — Living systematic review — Open source
  18. Systematic review of mental health, cognition and wellbeing interventions in Long COVID — Systematic review — Open source
  19. RECOVER-NEURO randomized cognitive intervention trial — Multicenter randomized trial — Open source
  20. Individual cognitive rehabilitation for Long COVID — Randomized trial — Open source
  21. Small-fiber neuropathy after COVID-19: retrospective case-control study — Retrospective case-control study — Open source
  22. RECOVER-VITAL: nirmatrelvir/ritonavir for established Long COVID — Phase 2 randomized placebo-controlled trial — Open source
  23. STOP-PASC nirmatrelvir/ritonavir trial — Randomized placebo-controlled trial — Open source
  24. Low-dose naltrexone for Long COVID: systematic review and meta-analysis — Systematic review and meta-analysis — Open source
  25. STIMULATE-ICP pharmacologic trial — Multisite open-label randomized controlled trial — Open source
  26. Low-dose aripiprazole in ME/CFS — Retrospective study — Open source
  27. Rituximab phase III ME/CFS trial — Randomized placebo-controlled phase III trial — Open source
  28. SIM01 synbiotic trial for post-acute COVID syndrome — Randomized double-blind placebo-controlled trial — Open source
  29. High-dose CoQ10 for post-COVID condition — Randomized double-blind crossover trial — Open source
  30. Specialist Long COVID integrated-care trial — Phase 3 cluster randomized trial — Open source
  31. HBOT sham-controlled Long COVID trial — Randomized double-blind sham-controlled trial — Open source
  32. Normobaric/hyperbaric oxygen Long COVID trial — Randomized placebo-controlled double-blind trial — Open source
  33. COVIVA taVNS pilot trial — Randomized sham-controlled pilot trial — Open source
  34. STIMULATE rivaroxaban result — Randomized controlled trial — Open source
  35. Rovunaptabin (BC007) reCOVer phase IIa — Exploratory randomized double-blind placebo-controlled phase IIa trial — Open source
  36. Guanfacine for marked Long COVID cognitive impairment: case report — Case report — Open source
  37. COVID-OUT metformin follow-up — Phase 3 randomized acute-COVID trial follow-up — Open source
  38. Metformin or UDCA for established PASC — Randomized double-blind placebo-controlled trial — Open source
  39. [Jason 2015]
  40. [mecfscliniciancoalition.org]
  41. [Holt-Lunstad 2015]
  42. [NICE]
Guide index

Useful next steps

Doctor prepDoctor handoutMy Fog
Related context

Clinical Summary

Thinking problems after COVID can include poor concentration, slow thinking, trouble finding words or mental exhaustion. Some people also have delayed symptom flares after activity.

High - NICE NG188/NG206

NICE NG188 Long COVID (updated Jan 2024); NICE NG206 ME/CFS (2021, surveillance 2025)

Last reviewed: 2026-03-23

Reviewed by: Dr. Alexandru-Theodor Amarfei, M.D.

Country Pathways

US: See Long COVID clinic or ME/CFS specialist

UK: See Long COVID clinic or ME/CFS specialist service

AU: See immunologist, cardiologist (for POTS), or ME/CFS clinic

Dietary Approach

Fatigue, nausea and difficulty preparing food can reduce intake. Keep meals manageable and ask for help with shopping or preparation when needed.

Supplements

  • Coenzyme Q10 (CoQ10/Ubiquinol) No CoQ10 dose is established for Long COVID brain fog. A trial in established post-COVID illness used high-dose CoQ10 and did not show a significant symptom benefit.A randomized crossover trial enrolled 121 participants and compared two six-week periods. CoQ10 did not significantly improve symptom number or severity versus placebo.
  • Creatine Monohydrate No dose is established for treating Long COVID brain fog. Discuss use first if you have kidney disease or take medicines that affect kidney function.Small preliminary studies don't show a reliable cognitive benefit for Long COVID.
  • Magnesium, ashwagandha and L-theanine combinations There is no established dose or tested combination for Long COVID brain fog.No Long COVID combination trial is cited here.
  • Butyrate (Sodium or Tributyrin) The cited studies don't set a dose for Long COVID brain fog.The cited papers examine mechanisms or dietary associations, not an established Long COVID treatment.

Connected Causes

Long COVID can affect several body systems. Sleep problems, symptoms while upright, migraine, medicine effects and mental health conditions can add to thinking problems. Assess each problem rather than assume that every symptom has one cause.