key: cord-1014538-7fblc2es
authors: Johansson, Madeleine; Ståhlberg, Marcus; Runold, Michael; Nygren-Bonnier, Malin; Nilsson, Jan; Olshansky, Brian; Bruchfeld, Judith; Fedorowski, Artur
title: Long-Haul Post–COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience
date: 2021-03-10
journal: JACC Case Rep
DOI: 10.1016/j.jaccas.2021.01.009
sha: 515a3e30ec9447ad1ccf168b01c9eafaec1e67dc
doc_id: 1014538
cord_uid: 7fblc2es

Major clinical centers in Sweden have witnessed an inflow of patients with chronic symptoms following initial outpatient care for coronavirus disease-2019 (COVID-19) infection, suggestive of postural orthostatic tachycardia syndrome. This report presents the first case series of 3 Swedish patients diagnosed with postural orthostatic tachycardia syndrome more than 3 months after the primary COVID-2019 infections. (Level of Difficulty: Beginner.)

P ostural orthostatic tachycardia syndrome (POTS) is the most prevalent chronic cardiovascular dysautonomia among young and middle-age individuals, predominantly women. It is characterized by chronic orthostatic intolerance, abnormal heart rate (HR) increase on standing, and deconditioning (1,2) ( Table 1) . The syndrome has been postulated to have post-viral autoimmune activation as a possible etiology (3) .

To raise awareness of POTS as a possible long-term complication following COVID-19 infection. To present diagnostic principles for an accurate POTS diagnosis. To propose treatment regimens in patient with persistent POTS symptoms.

tions including pneumonia, respiratory distress syndrome, liver injury, cardiac injury, and prothrombotic coagulopathy.

Long-term consequences remain unknown (4) . Recently, chronic ("long-haul") symptoms following COVID-19 infections have been consistent with a POTS-like presentation (4) . Here we present a series of 3 patients with chronic post-COVID-19 symptoms diagnosed as POTS.

In March 2020, a 42-year-old woman with history of allergic rhinitis and conjunctivitis developed flu-like symptoms including malaise, cough, fever, weakness, loss of appetite, myalgia, and loss of smell and taste. She did not seek medical attention and her condition improved progressively but, in May, symptoms recurred with the addition of abdominal pain and odynophagia. Chest computed tomography and laboratory testing were normal. A nasopharyngeal swab showed no evidence of COVID-19.

In July, debilitating symptoms of profound exhaustion with associated sinus tachycardia followed. Telemetry showed HR of 70 to 160 beats/ min. Echocardiography was normal. Serology tests for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) were considered borderline. By Sustained heart rate increment of not less than 30 beats/min or above 120 beats/min within 10 min of active standing or head-up tilt. For individuals who are younger than 19 years the required increment is at least 40 beats/min.

Absence of orthostatic hypotension (i.e., sustained systolic blood pressure drop of not less than 20 mm Hg).

Reproduction of spontaneous symptoms such as light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, and fatigue. In some patients, tachycardia may evoke vasovagal syncope corresponding to spontaneous attacks from patient's history.

History of chronic orthostatic intolerance and other typical POTSassociated symptoms (for at least 6 months (1)).

Absence of other conditions provoking sinus tachycardia such as anxiety disorders, hyperventilation, anemia, fever, pain, infection, dehydration, hyperthyroidism, pheochromocytoma, use of cardioactive drugs (sympathomimetics, anticholinergics).

This table has been endoresed by the American Academy of Neurology, the American Autonomic Society, the American College of Cardiology, the American Heart Association, the European Federation of Autonomic Societies, the European Heart Rhythm Association, the European Society of Cardiology, and the Heart Rhythm Society. Adopted with permission from Fedorowski (1).

POTS ¼ postural orthostatic tachycardia syndrome. Nonpharmacological measures including increased fluid intake, compression stockings, and avoidance of orthostatic triggers were recommended. She did not tolerate beta-blockers due to worsened orthostatic intolerance, and ivabradine 7.5 mg twice a day was started ( Table 2 ) with substantial improvement, although the patient remains on sick leave.

A 28-year-old woman developed COVID-19 symptoms in May 2020 with fever, dyspnea, chest pain, lightheadedness, and headache. Polymerase chain reaction testing was positive for SARS-CoV-2. Previous medical history included arthroscopic meniscectomy, tonsillectomy, and discectomy. and H2 antihistamines but remains highly symptomatic and is on sick leave.

In May 2020, a 37-year-old man developed sore throat, fever, fatigue, muscle weakness, dry cough, and palpitations. He had a history of childhood sepsis Recommendations were given to increase fluid and salt intake and use compression socks ( Table 2) .

The patient received propranolol 10 mg Â3 times a day and pyridostigmine 10 mg Â3, the latter due to severe fatigue and muscle weakness. In addition to typical POTS symptoms he developed nausea, orbital edema, and gastrointestinal symptoms ( Figure 6 ).

Empirical treatment with H1 and H2 antihistamines was initiated due to suspected mast cell activation syndrome, with moderate clinical improvement.

Despite up-titration of propranolol and pyridostigmine, he is still highly symptomatic and on sick leave. Table 1) .

POTS affects primarily women (z80%) and is manifested by orthostatic tachycardia, in association with various symptoms including palpitations, dizziness, headache, fatigue, and blurred vision (1,2) ( Table 3) . The syndrome can be precipitated by viral illness or severe infection (5) in 30% to 50% of all patients. The mechanism of POTS is generally undetermined. Similarly, the mechanism of post-COVID-19 Patient #2 self-reported symptoms using a dedicated POTS symptom scoring questionnaire composed of 12 most commonly reported symptoms in POTS. Patients were asked to grade their symptoms using a VAS ranging from 0 (no symptom) to 10 (worst possible). Themaximum score is 120 points. A score >40 points likely indicates pathology. Abbreviations as in Figure 1 . Patient #3 self-reported symptoms using a dedicated POTS symptom scoring questionnaire composed of 12 most commonly reported symptoms in POTS. Patients were asked to grade their symptoms using a VAS ranging from 0 (no symptom) to 10 (worst possible). The maximum score is 120 points. A score >40 points likely indicates pathology. Abbreviations as in Figure 1 . Table 1) .

Available management protocols for POTS ( Table 2) aim at increasing intake of fluids (water) and salt, physical countermaneuvers, and individually adapted aerobic exercise in recumbent position (1, 5, 9) to help correct the physiological abnormalities.

Pharmacotherapy includes volume expanders, vasoconstrictors, and HR regulators but patients may remain symptomatic and incapable of work.

Much remains unknown about the specific mechanisms responsible for the POTS-like symptoms in post-COVID-19 patients or how long these symptoms will last but chronic symptoms are expected in a subset of patients based on this initial clinical experience.

The authors have reported that they have no relationships relevant to the contents of this paper to disclose. 

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management

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Autoimmunity in postural orthostatic tachycardia syndrome: current understanding

Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review

Postural orthostatic tachycardia syndrome (POTS): a critical assessment

A case report of postural tachycardia syndrome after COVID-19

New-onset postural orthostatic tachycardia syndrome following coronavirus disease 2019 infection

Testing for SARS-CoV-2 antibodies

Pharmacotherapy for postural tachycardia syndrome