POTS following SARS-CoV-2 infection
The COVID-19 pandemic has led to several prolonged symptoms, sometimes annoying or debilitating for patients. These longstanding symptoms are termed “long COVID”, “long-haul COVID”, or “chronic COVID”[25]. Many previously-infected SARS-CoV-2 individuals complain of palpitations triggered by minimal exertion or standing. These patients experience dyspnea, lightheadedness, fatigue and sweating following palpitation. Manifestations of this syndrome, to some extent, resemble those of post-traumatic stress disorder. However, many patients fulfilled the diagnostic criteria for POTS, which seemed to result from autonomic nervous system dysfunction (dysautonomia) triggered by the virus[26]. The weight loss and hypovolemia resulting from constitutional symptoms of SARS-CoV-2 infection can increase cardiac SNS outflow and predispose to orthostatic intolerance. On the other hand, COVID-associated anxiety and sleep disturbance can lead to a hyperadrenergic state which further increases the probability of dysautonomia.
The underlying pathophysiologic mechanisms include direct autonomic nervous system damage by the virus, hyperinflammatory response and cytokine storm, hypercoagulability state, and autoimmune reactions. The direct viral effect is binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed on autonomic neurons and sometimes followed by hyperadrenergic POTS[27]. However, the most probable mechanism of post-COVID-19 POTS is SARS-CoV-2-associated induction of autoimmunity through producing cross-reacting antibodies with autonomic ganglia and nerve fibers and neuronal or cardiovascular receptors. In addition, sympathetic overactivation induced by SARS-CoV-2 infection may lead to post-COVID POTS[28, 29].
Besides POTS, SARS-CoV-2 infection has caused other autonomic dysfunctions such as orthostatic hypotension (OH), neurocardiogenic syncope (NCS), vasovagal syncope (VVS), post-COVID-19 exacerbation of paroxysmal hypothermia and hyperhidrosis, and small fiber neuropathy with orthostatic cerebral hypoperfusion syndrome[30-32].
Previously, autonomic dysfunction had been reported following infection with bacteria (Borrelia burgdorferi, Mycoplasma pneumonia, Mycobacterium lepra, Clostridium tetani and Clostridium botulinum), viruses (HIV, HTLV-1, influenza virus, Epstein-Barr virus, West Nile virus and Rabies virus), and parasites (Trypanosoma cruzi)[33-36]. Hence, viral infections, including SARS-CoV-2, are established triggers for POTS and patients with POTS usually report a recent viral infection[16].
The incidence of dysautonomia in the settings of long COVID is estimated to be up to 25% and has presented up to several months after infection. It has affected females more than males and has been more common in the young population. Most cases have been reported to occur within one month of SARS-CoV-2 infection[37, 38]. The relationship between the severity of the causative SARS-CoV-2 infection and the incidence of POTS is not yet determined. Even mildly SARS-CoV-2 infected patients have experienced COVID-related dysautonomia; nonetheless, it has occurred more commonly in COVID patients with hypertension, obesity, or immunocompromise. It should be acknowledged that post-COVID patients presenting with tachycardia should be evaluated for meeting the associated criteria, as all of them do not necessarily have POTS[39-41].
The mentioned condition is not life-threatening but affects daily function and mood. Like long COVID, POTS severity can fluctuate unpredictably, making rehabilitation and return to work challenging[42]. It should be noted that since POTS is quite common in COVID-19 survivors, clinicians should be aware of the condition and refer any patient with compatible manifestations to a specialist to be screened for POTS and also exclude life-threatening events like myocardial injury[43].