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].