Cardiac Considerations for Athletes Post-COVID-19 Infection: A Guiding Light Through Uncharted Waters

Introduction

SARS-CoV-2, the cause of the COVID-19 pandemic, is a novel RNA virus that is transmitted by respiratory droplets/aerosols. Cardiovascular complications can occur according to 2 patterns of myocardial injury: either by indirect inflammatory response without cardiac symptoms, or predominant cardiac involvement such as fulminant myocarditis, arrhythmia, or other cardiovascular manifestations. Because of these concerns, it is important for the cardiology community to be cognizant of the possible cardiovascular manifestations of COVID-19. 

These concerns have been heightened in athletes. The apprehension regarding sudden cardiac arrest (SCA) — the leading medical cause of fatalities in athletes during sports and exercise^1,2 — increases as more high-profile athletes get infected with COVID-19 and potentially develop myocarditis. While being across a line of scrimmage or in the locker room may increase the risk of transmission, it is unknown how many athletes infected with SARS-CoV-2 will develop cardiac complications. This uncertainty represents a large, empty hole in our knowledge of COVID-19. The concern is that exercise after COVID-19 infection may lead to an increased incidence of SCA or development of cardiomyopathy over time. Moving forward, our goal is to navigate these uncharted waters³ in order to maximize the physical, mental, and social benefits of sports while minimizing unnecessary restriction. 

Toward Safe Harbor 

All athletes exercise toward some goal, including winning, greatness, improved health, service, and/or social connections. With the possibility of COVID-19 infection leading to myocarditis and increasing the risk of SCA, there must be a balance of this risk with the known benefits of continued athletic participation. Safety — as described by physician-astronaut James Bagian — “is nothing more or less than a description of the level of risk that an entity chooses to accept.”⁴ Therefore, physicians and sports cardiologists should advise athletes and recreational exercisers about the level of risk that they collectively choose to accept in allowing return to play. 

Whatever that risk, especially at the highest levels of competition, there is a desire for some pre-participation evaluation specific for COVID-19. In the early months of the pandemic, numerous experts (including Dr. Prutkin) published recommendations suggesting it prudent to adopt a broader view of the cardiovascular pre-participation evaluation, ensuring appropriate time to test for cardiovascular manifestations in order to minimize false reassurance.^5,6 As we recognize the limitations of existing data, current timelines to ensure athlete safety have been neither too aggressive nor too conservative.^7,8 Most of these statements attempt to stratify risk based on symptoms and need for hospitalization. Testing protocols include an ECG, and possibly troponin, echocardiogram, or cardiac MRI. The American Academy of Pediatrics recently released a more conservative interim guidance about return to sports for children and adolescents, stating that those with severe COVID-19 disease or multisystem inflammatory syndrome should be treated as if they had myocarditis and be restricted from exercise for 3-6 months.⁹ Those with moderate disease or any symptoms should have an ECG and potential referral to a pediatric cardiologist. As we approach 1 year since the pandemic began, we still do not know the frequency with which SARS-CoV-2 leads to cardiac complications or how to screen effectively for them. There remain basic questions that need to be considered to avoid driving our ship into the shore as we cross these choppy waters. 

Water Hazard #1: Who has been infected with SARS-CoV-2?

The initial challenge in offering guidance on safe participation after COVID-19 infection is ascertaining the full denominator of cases due to the absence of undiagnosed asymptomatic or mildly symptomatic cases. This stems from lack of testing, difficulty in obtaining quick results, and variability in testing with frequent false positive results, such as the recent controversy in the NFL when all tests were falsely positive over a weekend.¹⁰ Furthermore, the variability in presenting symptoms and lack of universal testing makes it difficult to diagnose all COVID-19 cases and limit the risk of transmission. While professional and high-level collegiate programs may be doing frequent testing, this isn’t necessarily the norm at all universities, and definitely not for recreational athletes. 

Water Hazard #2: Can we predict which patients with COVID-19 will have direct cardiac involvement? 

Prior coronavirus and influenza epidemics have led to a significant burden of cardiovascular disease.¹¹ However, with a higher prevalence and risk of transmission with SARS-CoV-2 compared to the early stages of prior respiratory epidemics, as well as more numerous publications with variable quality, the full magnitude of risk is unclear. Thus, the incidence of cardiac involvement with COVID-19 infection continues to be debated. 

There are 2 patterns of cardiac involvement with COVID-19: indirect myocardial injury from the inflammatory stage of the disease, and direct myocardial injury as seen in myocarditis. Cardiac biomarker studies suggest a very wide range (from 1% to 100%) of myocardial injury from COVID-19 due to variability in population studies and when the troponin is measured.¹² There is a general trend to a higher likelihood of myocardial injury with greater disease severity; however, there are no studies of cardiac injury in asymptomatic or mild, ambulatory infections. Furthermore, while troponin is a marker for myocardial injury, proper interpretation requires clinical context and an understanding of troponin assays. Hence, using cardiac biomarkers alone to ascertain the proportion of patients with indirect myocardial injury will likely lead to an erroneous estimation of long-term cardiac risk. 

The other well-publicized marker of myocardial involvement are changes on cardiac MRI (CMR). There has been debate on the significance of CMR findings in patients that recovered from COVID-19 infection. A small Chinese study demonstrated that previously hospitalized patients with persistent cardiovascular symptoms had increased edema and/or fibrosis on CMR despite normal high-sensitivity troponin levels.¹³ A German study that incorporated “home recovery” patients and compared them to risk factor-controlled patients also demonstrated an increase in edema and/or fibrosis on CMR.¹⁴ However, there was substantial overlap of the CMR findings between these groups, making inferences difficult. Another recent study demonstrated that not all late gadolinium enhancement (LGE) on CMR in athletes after COVID-19 is myocarditis. While 46% had LGE, only 15% of patients post-COVID-19 met imaging criteria for myocarditis.¹⁵ Most of these CMR studies do not have matched groups of non-infected athletes as a control and do not have pre-COVID-19 or a second post-COVID-19 MRI comparison. As some of these imaging findings are subtle, it is unknown what the inter-reader agreement would be.

In addition to the methodological concerns with these studies, another major limitation in interpreting this information is that we do not know the incidence or severity of CMR abnormalities after other respiratory infections relative to COVID-19. Furthermore, it remains unclear if abnormalities on CMR constitute direct myocardial involvement from COVID-19 or if they are a stigmata of indirect injury and/or co-existing cardiovascular comorbidities. It seems safe to state that a negative CMR is reassuring, but we do not know the implication of a positive CMR. What can be said is that routine CMR imaging for asymptomatic patients post-COVID-19 has no clinical role and that more research is needed on the implications of abnormal CMR findings. 

Water Hazard #3: Does COVID-19 cardiac involvement lead to SCA in otherwise healthy athletes? 

The major obstacle in our path towards safe harbor is the fact that we do not know if subclinical myocardial injury — elevated troponin, LGE, or edema on CMR — has similar risk of SCA compared to clinical myocarditis. Current estimates of sports-related SCA due to myocarditis range from 5-9% of total cardiac causes of death.^1,16-18 However, these estimates of SCA are hampered by limited study methodology, major discrepancies in case ascertainment, and heterogenous population comparisons. Some cases of SCA may not include a thorough autopsy, leading to speculation that subclinical myocarditis after seasonal respiratory infections may be a large component of these unknown cases. Thus, the true incidence of SCA from myocarditis in athletes is unknown, even before SARS-CoV-2. Currently, there appears to be a single known case of exercise-provoked SCA in a high-profile athlete that had recovered from COVID-19, but it has not been publicly reported if this death was due to myocarditis or another cause.¹⁹ 

Finding Safe Harbor

The Big Ten conference initially cancelled their fall football season in part because at least 10 athletes were diagnosed with myocarditis.²⁰ After new testing protocols and evaluation of the data, the season is now going forward. The same is true for the PAC-12 and other leagues that are continuing to play, as are countless youth, high school, and recreational athletes. We likely will not know the true incidence of COVID-19–related myocarditis in athletes until long after the pandemic is over, if then. As it stands today, there is an uncertain prevalence of infection and an even bigger enigma of who has developed myocarditis. Thus, with sports and recreational activity commencing prior to a vaccine, our current guiding light must incorporate emergency action plans, knowledge of how to perform CPR and use AEDs, and an awareness of what SCA looks like during sports. Some element of a pre-participation evaluation is reasonable, especially to assess symptoms (Figure 1). 

We are in the middle of our journey and have yet to fully commit to the level of risk we choose to accept. Reassuringly, there has not yet been an epidemic of acute heart failure from myocarditis or exercise-related SCD over these past few months, and current data does not demonstrate an unassailable cardiovascular risk in athletes after infection with SARS-CoV-2. Continued research, surveillance, and longitudinal follow-up studies are needed, but these will not be written until we reach harbor. Until then, we make our way through these uncharted waters hoping that we safely reach our destination. Contact the authors on Twitter: 

Mustafa Husaini, MD, (@husainim) and Jordan M. Prutkin, MD, MHS (@jordanprutkin)

Disclosures: The authors have no conflicts of interest to report regarding the content herein.

Now available: Don't miss EP Lab Digest's podcast with Dr. Husaini and Dr. Prutkin! 

1. Harmon KG, Asif IM, Maleszewski JJ, et al. Incidence, cause, and comparative frequency of sudden cardiac death in National Collegiate Athletic Association athletes: a decade in review. Circulation. 2015;132(1):10-19. doi:10.1161/CIRCULATIONAHA.115.015431
2. Jayaraman R, Reinier K, Nair S, et al. Risk factors of sudden cardiac death in the young: multiple-year community-wide assessment. Circulation. 2018;137(15):1561-1570. doi:10.1161/CIRCULATIONAHA.117.031262
3. Fauci AS, Lane HC, Redfield RR. Covid-19 - navigating the uncharted. N Engl J Med. 2020;382(13):1268-1269. doi:10.1056/NEJMe2002387
4. Bagian JP. How safe is safe enough for space and health care?: Communication and acceptance of risk in the real world. JAMA Neurol. 2019;76(4):399-401. doi:10.1001/jamaneurol.2018.4405
5. Baggish A, Drezner JA, Kim J, Martinez M, Prutkin JM. Resurgence of sport in the wake of COVID-19: cardiac considerations in competitive athletes. Br J Sports Med. 2020;54(19):1130-1131. doi:10.1136/bjsports-2020-102516
6. Phelan D, Kim JH, Chung EH. A game plan for the resumption of sport and exercise after coronavirus disease 2019 (COVID-19) infection. JAMA Cardiol. 2020 May 13. doi:10.1001/jamacardio.2020.2136
7. Emery M, Phelan D, Martinez M. Exercise and athletics in the COVID-19 pandemic era. American College of Cardiology. Published May 14, 2020. Available at https://www.acc.org/latest-in-cardiology/articles/2020/05/13/12/53/exercise-and-athletics-in-the-covid-19-pandemic-era. Accessed September 4th, 2020.
8. Baggish AL, Levine BD. Icarus and sports after COVID 19: too close to the sun? Circulation. 2020;142(7):615-617. doi:10.1161/CIRCULATIONAHA.120.048335
9. COVID-19 interim guidance: return to sports. American Academy of Pediatrics. Published September 18, 2020. Available at https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-interim-guidance-return-to-sports/. Accessed September 21, 2020.
10. Seifert K. All of NFL’s positive coronavirus tests from the weekend return negative. ESPN. Published August 24, 2020. Available at https://www.espn.com/nfl/story/_/id/29729892/source-all-77-nfl-positive-tests-return-negative. Accessed September 4, 2020.
11. Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020;41(19):1798-1800. doi:10.1093/eurheartj/ehaa231
12. Sandoval Y, Januzzi JL, Jaffe AS. Cardiac troponin for assessment of myocardial injury in COVID-19: JACC review topic of the week. J Am Coll Cardiol. 2020;76(10):1244-1258. doi:10.1016/j.jacc.2020.06.068
13. Huang L, Zhao P, Tang D, et al. Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging. JACC Cardiovasc Imaging. 2020 May 12;S1936-878X(20)30403-4. doi:10.1016/j.jcmg.2020.05.004
14. 1Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Jul 27;e203557. doi:10.1001/jamacardio.2020.3557
15. Rajpal S, Tong MS, Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol. 2020 Sep 11;e204916. doi:10.1001/jamacardio.2020.4916
16. Marijon E, Tafflet M, Celermajer DS, et al. Sports-related sudden death in the general population. Circulation. 2011;124(6):672-681. doi:10.1161/CIRCULATIONAHA.110.008979
17. Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349(11):1064-1075. doi:10.1056/NEJMra022783
18. Bagnall RD, Weintraub RG, Ingles J, et al. A prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016;374(25):2441-2452. doi:10.1056/NEJMoa1510687
19. Press A. Former Florida state center Michael Ojo dies during workout in Serbia. Sports Illustrated. Published August 7, 2020. Available at https://www.si.com/college/2020/08/07/michael-ojo-dies-collapses-workout-serbia-florida-state. Accessed September 4, 2020.
20. Goldberg R. Report: at least 10 Big Ten football players have heart condition myocarditis. Bleacher Report. Published August 11, 2020. Available at https://bleacherreport.com/articles/2904115-report-at-least-10-big-ten-football-players-have-heart-condition-myocarditis. Accessed September 4, 2020.