POTS in Long-COVID: The hidden culprit of chronic fatigue and dizziness

POTS is a form of dysautonomia, a disorder of the autonomic nervous system manifested by an increase in heart rate by a minimum of 30 beats per minute when the body is upright, without a decrease in blood pressure. Symptoms of POTS include:

• Heartworms,
• Dizziness and weakness when changing positions,
• Chronic fatigue,
• Brain fog (problems with concentration and memory),
• Headaches and muscle weakness.

Interestingly, POTS symptoms can appear both during COVID-19 infection and many months later, despite recovery from the acute phase.

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Diagnosis and treatment of POTS in Long COVID

POTS can be diagnosed in the doctor's office, based on orthostatic tests. In inconclusive cases, a tilt-table test is worth considering. Treatment is based on strategies familiar from classic POTS:

• Blood pressure support:

- Salt supplementation and adequate hydration,

- Use of compression stockings to improve venous circulation.

• Physical activity:

- Despite concerns about exhaustion, the 2024 study suggests that graded physical activity does not harm Long COVID patients, and in fact promotes recovery. Moderate-intensity exercise, similar to that recommended for ME/CFS and fibromyalgia, is indicated.

• Pharmacotherapy:

- Propranolol and midodrine effectively relieve orthostatic symptoms,

- Low-dose naltrexone (LDN), increasingly being studied in Long COVID, has shown potential in reducing the neuroinflammatory substrate of dysautonomia, consistent with its efficacy in fibromyalgia.

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Prognosis and challenges

Although in many patients the symptoms of POTS resolve within 12 months, for some people the disorder becomes a cause of severe limitations in daily functioning. Therefore, it is crucial to further investigate the mechanisms of Long COVID and to develop effective therapeutic strategies to speed up recovery.

POTS therapy

Long COVID and its complications, such as POTS, show how complicated the impact of SARS-CoV-2 infection can be on the autonomic and immune systems. POTS therapy requires a holistic approach, combining pharmacotherapy, appropriate diet, physical activity and psychological support.

It is encouraging to see that research on low-dose naltrexone (LDN) is gaining increasing attention, especially in the context of the treatment ofLong-COVID syndrome. The drug, known to treat fibromyalgia, various autoimmune diseases and other chronic inflammatory conditions, among others, as it turns out, may prove to be a valuable tool inLong-COVID as well. However, the key challenge remains, of course, the individualization of treatment and further clinical studies to better understand the mechanisms of this disease.

Propranolol is an inexpensive, accessible and well-known B-blocker non-selective drug, while midodrine is available in Poland under the trade name Gutron. It is a drug used to treat severe orthostatic hypotension, a significant drop in blood pressure with a change in body position. Both drugs together with LDN therapy, which is gaining popularity, appear to be useful for patients with symptoms of POTS, a consequence of Long-COVID.

The dose of propranolol and midodrine and the dosage of LDN is determined by a doctor who is caring for the patient and has experience in LDN therapy - individually for each patient, depending on the severity of symptoms and response to treatment.

Therapy of postural orthostatic tachycardia syndrome POTS requires a multifaceted approach that includes medications, lifestyle modification and symptomatic support. The three medications used to treat POTS in the course of Long COVID are, as I mentioned earlier, propranolol , midodrine and low-dose naltrexone (LDN).

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• LDN (Low-Dose Naltrexone) in POTS.

LDN, or low-dose naltrexone (typically used in doses ranging from 1.5-4.5 mg), is increasingly used as adjunctive therapy for chronic conditions such as POTS, fibromyalgia and Long COVID neuroinflammatory symptoms.

Mechanism of action of LDN in POTS:

• Reduction of neuroinflammatory mechanisms: LDN modulates microglia in the nervous system, reducing the neuroinflammatory substrate of dysautonomia.
• Immunomodulatory effects: Naltrexone in low doses acts on opioid receptors, raising endorphin levels and reducing excessive activation of the immune system.
• Improves symptoms of fatigue and brain fog: Supports cognitive function and reduces fatigue, which are common in patients with Long COVID.

Method of taking LDN:

1. Initial dosage: 1.5 mg daily before bedtime.
2. Gradual increase: Each week, the dose can be increased by 0.5-1.5 mg until the target dose of 4.5 mg per day is reached.
3. Form of the drug: LDN must be prepared in a recveptur pharmacy, as standard tablets contain higher doses - amounting to 50 mg.

Relevant comments:

• LDN is well tolerated, but in the initial phase in rare cases headaches or vivid dreams may occur, which usually disappear after a few days. Therefore, in my opinion, it is safer to start therapy with a dose of 0.5 mg, increased every 7-14 days, depending on the patient's response.
• Treatment should be monitored by a physician experienced in LDN therapy to adjust the dose according to the patient's individual response.

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• Propranolol in POTS

Propranolol is a beta-blocker that effectively relieves the symptoms of POTS by controlling heart rate and reducing the workload on the heart. It is one of the most commonly used drugs to treat the condition.

Mechanism of action of propranolol in POTS:

• Control of orthostatic tachycardia: Propranolol reduces excessive increases in heart rate when the body is upright.
• Reduction of adrenergic symptoms: The drug reduces symptoms such as palpitations, anxiety and muscle tremors.
• Improving exercise tolerance: By improving cardiac control, propranolol enables patients to gradually return to physical activity.

How to take propranolol:

1. Initial dosage: usually start with 10-20 mg 2-3 times a day.
2. Gradual modification: the dose can be gradually increased depending on symptoms, but usually does not exceed 80-120 mg per day.
3. Timing of intake: Propranolol is best taken before situations that increase symptoms (such as in the morning or before activity).

Important Notes:

• Propranolol treatment should be monitored to avoid excessive lowering of blood pressure and bradycardia (too slow a heart rate).
• Propranolol can cause fatigue or cold extremities, especially during the initial phase of treatment.

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Summary of LDN and propranolol therapy in POTS in Long COVID

• LDN has immunomodulatory and neuroprotective effects, alleviating symptoms of fatigue, brain fog and the neuroinflammatory substrate of POTS.
• Propranolol effectively controls tachycardia, improving patients' comfort and tolerance of upright standing.

Therapy with both drugs should be individualized and supervised by a physician to take into account the patient's tolerance and the body's response to treatment. Combining pharmacotherapy with lifestyle modification (hydration, salt, physical activity) increases the effectiveness of therapy and gives patients a chance for a better quality of life in their struggle with POTS and Long COVID.

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Use of midodrine in POTS during the course of Long COVID

Midodrine is a drug used to treat orthostatic hypotension and symptoms associated with POTS (postural orthostatic tachycardia syndrome). In the course of Long COVID, when autonomic nervous system function is impaired, midodrine can significantly improve patients' quality of life by stabilizing blood pressure and reducing orthostatic symptoms.

Mechanism of action of midodrine

Midodrine acts as an agonist of alpha-adrenergic receptors in blood vessels, resulting in:

1. Vasoconstriction (vasoconstriction): Increases vascular wall tension, which helps prevent blood pressure drops during body uprighting.
2. Improves venous return: Reduces blood stasis in the lower extremities, a common cause of dizziness and fainting.

In POTS, midodrine helps reduce orthostatic symptoms, such as:

• Dizziness and weakness on verticalization,
• Acceleration of the heart rate (tachycardia),
• Fatigue and a feeling of "brain fog."

How to take midodrine

• Initial dosage:

- Treatment is usually started with 2.5 mg of midodrine 2-3 times a day.

• Gradually increase the dose:

- The dose can be gradually increased every few days or weeks depending on the patient's response to treatment.

- The typical therapeutic dose is 5-10 mg 2-3 times a day.

• Hours of taking the drug:

- Midodrine is taken during the day (usually in the morning and afternoon).

- Do not take the drug in the evening or before bedtime, as it can lead to an increase in blood pressure when lying down (nocturnal hypertension).

• Monitoring:

- Regular monitoring of blood pressure while sitting, standing and lying down is essential to avoid excessive increases in blood pressure.

- Patients should be monitored for side effects such as a cold feeling in the extremities, tingling skin or "goosebumps."

Guidelines for the use of midodrine

• Hydration and diet: the drug works more effectively if the patient is adequately hydrated. It is also recommended to consume more salt (unless contraindicated).
• Avoiding prolonged sitting or standing: Changes in body position that promote circulation are helpful.
• Wearing compression stockings: Combined with midodrine, they reduce symptoms associated with blood pooling in the lower extremities.

Contraindications and side effects

Midodrine is not suitable for all patients. Contraindications include:

• Hypertension,
• Heart Diseases,
• Kidney diseases without proper surveillance.

Most common side effects:

• Cold hands and feet,
• Tingling or goosebumps,
• Elevated blood pressure when lying down (nocturnal hypertonia).

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Summary

Midodrine is an effective drug in the treatment of POTS in the course of Long COVID, especially in patients with severe orthostatic symptoms. Due to its effect of increasing vascular tone and improving venous return, it can significantly improve patients' comfort. However, treatment with midodrine should be supervised by a physician who will assess the safety and efficacy of the therapy and adjust the dosage to the individual patient's needs.

It is worth remembering that POTS and Long COVID require interdisciplinary cooperation of specialists and patient education to understand that gradual recovery is possible.

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Reproduced from: Management of POTS due to Long COVID, Lilian White, MD - American Family Physician Blog. November 4, 2024