Can a patient with normal thyroid levels but very high Thyroid Peroxidase (TPO) antibody levels experience fatigue, brain fog, exercise intolerance, and heat intolerance in the context of long COVID or post-COVID?

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High TPO Antibodies in Long COVID: Relationship to Symptoms

Patients with normal thyroid levels but high thyroid peroxidase (TPO) antibody levels can experience fatigue, brain fog, exercise intolerance, and heat intolerance in long COVID, as there is a statistical association between elevated anti-TPO antibodies and long COVID symptoms. 1

Thyroid Dysfunction and Autoimmunity in Long COVID

Thyroid Antibodies and Long COVID

  • Recent evidence shows a significant association between highly elevated anti-TPO antibodies and long COVID symptoms, even in patients with normal thyroid function tests 1
  • Studies have observed incident anti-TPO positivity following COVID-19 infection, with significant increases in anti-TPO titers during convalescence 2
  • Factors associated with significant increases in anti-TPO titers include:
    • Worse baseline clinical severity of COVID-19 2
    • Elevated C-reactive protein during hospitalization 2
    • Higher baseline anti-TPO titer 2

Neurological Symptoms in Long COVID

  • Neurological and cognitive symptoms are major features of long COVID, including:
    • Fatigue (found in 32% of patients at 12 weeks post-infection) 3
    • Cognitive impairment/brain fog (found in 22% at 12 weeks) 3
    • Exercise intolerance and postexertional malaise 3
    • Heat intolerance (part of dysautonomia spectrum) 3

Pathophysiological Mechanisms

  • Brain fog in long COVID is primarily caused by neuroinflammation, blood-brain barrier disruption, cerebral hypometabolism, and vascular dysfunction 4
  • Activation of the kynurenine pathway has been identified in long COVID and is associated with cognitive impairment 3
  • Dysautonomia, particularly POTS, is commonly found in long COVID (67% in one cohort), which can explain symptoms like heat intolerance 3
  • Immune dysregulation appears to be a key mechanism in long COVID, which may explain the connection between thyroid autoimmunity and symptoms 3

Clinical Implications

Relationship Between Thyroid Antibodies and Symptoms

  • While baseline or follow-up thyroid function tests were not associated with long COVID occurrence, patients with positive anti-TPO antibodies showed different patterns of symptom resolution 5
  • A 2024 study found a statistical association between long COVID symptoms and highly elevated anti-TPO antibodies, even in euthyroid individuals 1
  • These patients also showed strongly elevated SARS-CoV-2-specific T cell responses and moderately raised anti-spike IgG levels even 23 months post-infection 1

Monitoring and Management

  • Patients with long COVID symptoms should be monitored for thyroid dysfunction, as incident thyroid autoimmunity has been observed following COVID-19 2
  • For patients with normal thyroid function but high TPO antibodies experiencing fatigue, brain fog, and exercise intolerance:
    • Pacing is recommended for managing postexertional malaise 3
    • Exercise should be avoided as it worsened the condition in 75% of long COVID patients 3
    • Consider evaluating for POTS, which may explain some symptoms 3

Important Caveats

  • The exact etiological link between elevated anti-TPO antibodies and long COVID symptoms remains unclear 1
  • Most abnormal thyroid function tests observed during acute COVID-19 resolve during convalescence 2
  • The presence of high TPO antibodies with normal thyroid function may represent early thyroid autoimmunity that has not yet progressed to clinical thyroid dysfunction 5
  • Female sex and higher viral load during acute COVID-19 are independent predictors of long COVID, which should be considered when evaluating patients 5

Conclusion

While patients can have normal thyroid levels with high TPO antibodies and experience typical long COVID symptoms, the relationship is complex and still being elucidated. Current evidence suggests monitoring these patients for future thyroid dysfunction while managing their long COVID symptoms according to established guidelines.

References

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Guideline

Brain Fog in Long COVID

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2021

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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