POTS After COVID: Insights into Post-Viral Autonomic Issues

Some individuals recovering from COVID-19 report lingering symptoms that affect daily life, including dizziness, rapid heart rate, and fatigue upon standing. These issues often point to postural orthostatic tachycardia syndrome (POTS), a form of autonomic dysfunction that has gained attention as a post-viral complication.

Understanding how COVID-19 triggers POTS is essential for improving diagnosis and treatment. Researchers are investigating the mechanisms behind this phenomenon and how it compares to other post-infectious autonomic disorders.

Autonomic Dysfunction After Infection

The autonomic nervous system (ANS) regulates involuntary physiological functions such as heart rate, blood pressure, digestion, and temperature control. When disrupted after an infection, individuals may experience dysregulation of these processes. Post-viral autonomic dysfunction has been documented in various infectious diseases, but the emergence of POTS after COVID-19 has drawn attention due to its impact on cardiovascular stability and overall well-being.

Following infection, the ANS may struggle to maintain homeostasis, leading to orthostatic intolerance, excessive heart rate fluctuations, and abnormal blood pressure responses. In post-COVID POTS, patients frequently report an exaggerated heart rate increase upon standing—exceeding 30 beats per minute (bpm) in adults or 40 bpm in adolescents—often causing dizziness, palpitations, and exercise intolerance. Many also experience gastrointestinal disturbances, thermoregulatory issues, and cognitive dysfunction, indicating widespread autonomic involvement.

The persistence of autonomic dysfunction varies. Some individuals recover within months, while others experience prolonged impairment. Similar patterns have been observed after Epstein-Barr virus, influenza, and other viral infections, but post-COVID autonomic issues appear more widespread. This has led researchers to investigate whether SARS-CoV-2 has distinct effects on autonomic regulation compared to other pathogens.

Clinical Features

Patients with post-COVID POTS report more than just heart rate abnormalities. A defining feature is a pronounced increase in heart rate upon standing, often exceeding diagnostic thresholds within 10 minutes. This tachycardic response is accompanied by lightheadedness, palpitations, and, in some cases, near-syncope. Unlike orthostatic hypotension, blood pressure in POTS patients typically remains stable.

Profound fatigue is another hallmark symptom. This exhaustion is not simply due to deconditioning but appears linked to autonomic dysfunction. Many patients describe a delayed recovery after physical or cognitive exertion, known as post-exertional malaise, a symptom also seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Cognitive difficulties, often referred to as “brain fog,” are another common complaint. Patients struggle with memory, concentration, and processing speed, which can interfere with daily tasks. Research suggests inadequate cerebral perfusion during upright posture may contribute to these impairments.

Gastrointestinal symptoms, including nausea, bloating, and altered bowel habits, are frequently reported, pointing to enteric nervous system dysregulation. Some individuals experience delayed gastric emptying, leading to early satiety and discomfort after meals. Thermoregulatory abnormalities, such as excessive sweating or an inability to sweat appropriately, further underscore the widespread autonomic involvement in post-COVID POTS.

Proposed Biological Pathways

The development of POTS after COVID-19 likely stems from multiple physiological disruptions. While the exact mechanisms remain under investigation, researchers have identified three primary pathways: autoimmune mechanisms, neurological changes, and vascular dysregulation.

Autoimmune Mechanisms

One hypothesis involves an autoimmune response triggered by the infection. Studies have identified autoantibodies targeting adrenergic and muscarinic receptors, which regulate autonomic function. A 2021 study in Nature Cardiovascular Research found elevated levels of these autoantibodies in POTS patients, suggesting immune dysregulation may interfere with cardiovascular control.

Some patients exhibit symptoms overlapping with autoimmune conditions like small fiber neuropathy, which affects peripheral nerve function. Symptom improvement with immunomodulatory treatments such as intravenous immunoglobulin (IVIG) and corticosteroids further supports an immune-mediated component, though responses vary, indicating autoimmunity is likely one of several contributing factors.

Neurological Changes

SARS-CoV-2 affects the nervous system, potentially leading to long-term autonomic dysfunction. Neuroinflammation, triggered by the virus or the body’s immune response, may disrupt autonomic pathways in the brainstem and peripheral nervous system. A 2022 study in Brain, Behavior, and Immunity found elevated inflammatory markers in cerebrospinal fluid from individuals with post-COVID neurological symptoms, suggesting persistent neuroinflammation could contribute to dysautonomia.

Damage to small autonomic nerve fibers has also been observed in some POTS patients, impairing communication between the nervous and cardiovascular systems. Skin biopsies from affected individuals have shown reduced nerve fiber density, a hallmark of small fiber neuropathy. While nerve regeneration is possible, recovery timelines vary, and some patients experience prolonged dysfunction.

Vascular Dysregulation

Abnormal vascular function may also contribute to post-COVID POTS. Some patients exhibit excessive venous pooling in the lower extremities upon standing, leading to inadequate blood return to the heart and compensatory tachycardia. A 2023 study in Circulation Research found evidence of endothelial dysfunction in post-COVID patients, characterized by impaired nitric oxide production and increased vascular stiffness, which can affect circulation and autonomic stability.

Altered blood vessel reactivity may contribute to dizziness and exercise intolerance. Some individuals with post-COVID POTS demonstrate exaggerated vasoconstriction or inappropriate vasodilation, complicating blood pressure regulation. These findings suggest SARS-CoV-2 may induce lasting vascular changes, either through direct viral effects on endothelial cells or secondary inflammatory processes.

Diagnostic Considerations

Diagnosing POTS after COVID-19 requires a detailed clinical assessment, as symptoms overlap with other autonomic disorders. The primary criterion is an excessive heart rate increase upon standing—exceeding 30 bpm in adults or 40 bpm in adolescents within 10 minutes—without a significant blood pressure drop. This is confirmed using a 10-minute active stand test or a tilt table test. Patients often describe dizziness, palpitations, and fatigue, making differentiation from deconditioning or anxiety-related tachycardia essential.

Beyond heart rate abnormalities, autonomic reflex screening assesses sweat production, blood pressure variability, and baroreflex sensitivity. Some individuals exhibit additional dysautonomic signs, such as abnormal pupillary responses or reduced heart rate variability, indicating broader autonomic dysfunction. Given the frequent presence of non-cardiovascular symptoms, a multidisciplinary approach involving neurologists, cardiologists, and gastroenterologists is often necessary.

Comparison With Other Post-Infectious Dysautonomias

Post-viral autonomic dysfunction has been observed after infections such as Epstein-Barr virus (EBV), influenza, and human immunodeficiency virus (HIV). However, the high incidence of POTS after SARS-CoV-2 has raised questions about whether this virus exerts distinct effects on autonomic regulation. While post-infectious dysautonomia has been documented for decades, the scale and complexity of post-COVID cases suggest a broader systemic impact involving multiple mechanisms.

Compared to POTS triggered by other infections, post-COVID cases often present with more severe exercise intolerance, cognitive dysfunction, and persistent fatigue. While autonomic disturbances following EBV or influenza typically resolve within months, post-COVID POTS appears more prolonged and unpredictable. Some studies suggest SARS-CoV-2 induces persistent endothelial dysfunction and inflammatory changes, prolonging autonomic instability.

Clinicians have also noted overlap between post-COVID POTS and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition characterized by autonomic and metabolic abnormalities. This raises the possibility that post-COVID dysautonomia shares underlying mechanisms with other post-viral syndromes, necessitating treatment approaches that address both autonomic instability and broader systemic dysfunction.