Post COVID-19 Autonomic Dysfunction in Athletes
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Camille Frazier-Mills, MD Duke University
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Post COVID-19 Autonomic Dysfunction in Athletes
- 1. Post COVID 19 Autonomic Dysfunction in Athletes Camille Frazier-Mills, MD MHS FACC FAHA Professor of Medicine Duke Electrophysiology
- 2. Disclosures • Medtronic, Research and Consulting • Johnson & Johnson DEI Advisory
- 3. COVID 19 • 774 million cases and over 7 million deaths worldwide (2.1% mortality rate) • Chronic symptoms have been reported in up to 50% of survivors • Post infectious autonomic dysfunction has been reported in other recent pandemics such as SARS 2002-2004 (29%) • Post Acute COVID Syndrome or “Long haul” now described for COVID 19 with >65 million affected reported in 2023 Auton Neurosci. 2021 Nov; 235: 102841 https://www.who.int/health-topics/coronavirus#tab=tab_1 accessed 4/6/2024
- 4. Definitions Int. J. Environ. Res. Public Health 2021, 18(5), 2621 Int. J. Environ. Res. Public Health 2021, 18(10), 5329
- 5. National Institute for Health and Care Excellence (NICE) Definition • “Post COVID-19 syndrome” or “Long COVID” as a set of persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks after illness and which are not explained by an alternative diagnosis
- 6. Nature Medicine volume 27, pages601–615 (2021) Nature Reviews Neurology | Volume 20 | February 2024 | 99–113
- 7. Autonomic Lesion and Clinical Manifestations Nature Reviews Neurology | Volume 20 | February 2024 | 99–113
- 8. Mechanism of Action of ANS Involvement in PACS • Viral mediated and immune mediated disruption of autonomic NS • Cytokine storm induced by the virus occurs due to sympathetic activation causing proinflammatory cytokine release • Virus itself causes immune mediated neurological syndrome such as POTS, IST, or OH associated with autoantibodies and adrenergic modulation Clin Med (Lond). 2021 Jan; 21(1): e63–e67. Nature Medicine volume 27, pages601–615 (2021)
- 9. Post Acute COVID Syndrome • >50% of patients have residual symptoms beyond 6 months from infection • Neurological symptoms may be common, as cognitive deficits have been reported in 36% of patients two to four months after COVID-19 • A series reported typical features of orthostatic intolerance, fatigue, palpitations, lightheadedness, and activity intolerance in post-COVID individuals • Autonomic testing found heterogeneous responses, including OH and POTS, and baroreflex failure Lancet. 2021;397:220–232. doi: 10.1016/S0140-6736(20)32656-8. Goodman BP et al (2021) COVID-19 dysautonomia. Front Neurol 12:624968 Blazhenets G et al (2021) J Nucl Med.
- 10. https://doi.org/10.1016/j.ahjo.2021.100025 Post Acute COVID Syndrome Evaluation
- 11. Auton Neurosci. 2021 Nov; 235: 102841
- 12. • Estimate the prevalence of reported COVID-19, symptomatic COVID-19, and Long COVID in college athletes in the United States attending 18 schools from spring 2020 to fall 2021 • 18 collegiate school administrators, representing about 7,000 student-athletes • BMC Infect Dis. 2023; 23: 876
- 13. Clinical Pattern and Impact of COVID 19 in International Athletes Br J Sports Med 2022;56:4–11
- 14. PACS in Elite Athletes • 84 Belgium football players, 22 infected with SARS-CoV-2 during follow up • Strength and aerobic performance tested pre and post COVID throughout the season • Post COVID HR higher after COVID infection compared to noninfected • Decreased function in aerobic testing • No difference in strength and sprint testing Ann Med. 2023; 55(1): 2198776
- 15. PACS in Elite Athletes Ann Med. 2023; 55(1): 2198776
- 16. Recovery of performance and persistent symptoms in athletes after COVID-19 • . Br J Sports Med 2022;56:4–11. PLoS ONE 17(12): e0277984.
- 17. Recovery of performance and persistent symptoms in athletes after COVID-19 PLoS ONE 17(12): e0277984.
- 18. Management of Post COVID Orthostatic Intolerance • Education • Exercise • Fluid and salt • Avoid exacerbating factors • Compression • Pharmacological treatment including fludrocortisone, midodrine, propranolol, ivabradine and with hyperadrenergic response methyldopa or clonidine; immune mediated-IVIG https://doi.org/10.1016/j.jacc.2018.11.059
- 19. Potential Benefits of Exercise in PACS Int. J. Environ. Res. Public Health 2021, 18(10), 5329;
- 20. Nature Medicine volume 27, pages601–615 (2021)
- 21. Case Presentation • 19 yo student-athlete presents for evaluation of CP, palpitations, and near- syncope for 4 months developing after confirmed COVID-19 Symptoms were noticed 3-4 weeks after acute infection and persisted. Pt previously exercised vigorously without limitation. No full syncope. She drinks 2-3L water per day • In clinic, EKG showed sinus tachycardia at 105 bpm. Normal axis and intervals • Echo was without evidence of significant structural disease, EF >55%, no effusion • Cardiac MRI showed no evidence of myocarditis
- 22. • Orthostatics: • Lying 87 108/62 POX 99% • Seated 96 106/58 • Standing 122 106/68 • Labs returned with normal hgb, cortisol, thyroid function, mayo dysautonomia panel Case Presentation • She was diagnosed with PACS with POTS physiology • She was advised to drink 4L water and add electrolytes (high sodium concentration) • Increase sodium to 6+ gm per day • Wear compression (abdominal binder or compression tops) • Discussed low-dose b-blocker, prn considered • Start reduced exercise and titrate up
- 24. Case Presentation • Pt was seen back in the clinic in 4-6 weeks and was feeling better • Exercise tolerance increased and she was cycling (modified) and doing light weights • Pt returned 2 months later and was exercising vigorously and wanted to wean b-blocker • Attempted 1-month wean of b-blocker, but had recurrence of symptoms, so slowly weaned over 2-3 months • Pt now is doing well, but must continue with aggressive hydration, salt and compression and continued exercise
- 25. Conclusion • Post Acute COVID 19 Syndrome (PACS) is a syndrome with a constellation of symptoms from the sequelae of disease and often autonomic dysfunction • Autonomic manifestations vary and may include CP, palpitations, lightheadedness, GI concerns, and cognitive dysfunction • Evaluation with autonomic testing and tilt table testing can be useful • Education, social support, exercise training, and medications can be useful to improve symptoms
Editor's Notes
- Here are my disclosures.
- As you know the impact of the pandemic has been profound. As of 10/8/2021, there has been over 237 million cases and mortality is greater than 4.9 million worldwide. Chronic symptoms have been reports in up to 50% of survivors with numbers varying with severity of illness. Post infection autonomic dysfunction has been reported with other virus and with other recent pandemic such as SARS pandemic in 2002-2004. 29% of survivors from that pandemic had autonomic dysfunction. Now we are seeing similar finding associated with COVID 19 described as PACS or long haul
- So, let’s start with definitions. There are many nomenclatures in the literature, but the most consistent description is Post-Acute Covid Syndrome (PACS) divided into acute, long and persistent. Acute PACS is described as symptoms which occur after infection and persist up to 12 weeks, long is up to 24 weeks and persistent is beyond 24 weeks. The starting point may vary depending on severity of symptoms but ranges 3-5wks post onset of COVID acute infection
- The NICE definition, often used in the literature, describes PACS as persistent physical, cognitive, and psychological symptoms that continue for >12 week and not explained by an alternative diagnosis.
- nice review article was published in nature this year which summarizes some of the finding in PACS.
- This table show the persistence of symptoms several months out from acute infection affecting different populations across the world with common complaints concerning CV, neuropsychological, GI, most with autonomic involvement.
- When we review the potential mechanism of action leading to autonomic symptoms, 2 theories exist: direct viral mediated toxicity or immune mediated toxicity. With direct viral attack, endothelial damage occurs leading to microvascular injury. This leads to further immune system dysregulation and hyperinflammatory state. The resulting endothelitis can lead to maladaption of the RAAS affecting the ACE2 pathway Additionally, the cytokine storm induced by covid 19 leads to sympathetic activation and pro inflammatory cytokine release. The combination cause autoantibodies and adrenergic modulation causing neurally mediated syndromes such as POTS, IST or OH.
- So how does PACS present 50% of patient have residual symptoms beyond 6 months of infection. Neurological symptoms such as cognitive impairment or brain fog has been reported in 36% patients Orhtosttatic intolerance with fatigue, decreased exercise tolerance palpitations, and near syncope. AAutonomic testing found heterogeneous responses, including OH and POTS, and baroreflex failure
- Other case reports and case series have shown association with POTS and exacerbating OH. With good response to treatments provided.
- So the management of PACS depends on the symptoms and finding with testing. In general, education, avoidance of triggers, expanding volume with fluid and salt, wearing compression have all been associated with better outcomes. The pharmacologic treatment depends on presenting symptoms and testing, but in the cardiology realm considerations would be Fludrocortisone, MIDORINE, pyridostigmine, B-BLOCKERS, IVABRADINE, AND WITH HTN RESPONSE, METHYLDOPA AND POSSIBLE CLONIDINE
- Exercise has also been examined in PACS and appears beneficial due to numerous effects
- In conclusion, patients with PACS should be evaluated due to persistent symptoms. A multidisciplinary approach would be beneficial to address the sequela of disease from acute infection and the potential autonomic effects. Intensive education, therapy (physical, occupational, and psychological), and close follow up with providers is necessary
- I will close with a case that had a good result but persistent symptoms for nearly a year.