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Abstract
Objective Longitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the highest level of sports and exercise.
Methods This prospective controlled study included elite athletes from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise cohort. Athletes infected with SARS-CoV-2were offered structured, additional cardiovascular screenings, including cardiovascular MRI (CMR). We compared ventricular volumes and function, late gadolinium enhancement (LGE) and T1 relaxation times, between infected and non-infected elite athletes, and collected follow-up data on cardiac adverse events, ventricular arrhythmia burden and the cessation of sports careers.
Results We included 259 elite athletes (mean age 26±5 years; 40% women), of whom 123 were infected (9% cardiovascular symptoms) and 136 were controls. We found no differences in function and volumetric CMR parameters. Four infected athletes (3%) demonstrated LGE (one reversible), compared with none of the controls. During the 26.7 (±5.8) months follow-up, all four athletes resumed elite-level sports, without an increase in ventricular arrhythmias or adverse cardiac remodelling. None of the infected athletes reported new cardiac symptoms or events. The majority (n=118; 96%) still participated in elite-level sports; no sports careers were terminated due to SARS-CoV-2.
Conclusions This prospective study demonstrates the safety of resuming elite-level sports after SARS-CoV-2 infection. The medium-term risks associated with SARS-CoV-2 infection and elite-level sports appear low, as the resumption of elite sports did not lead to detrimental cardiac effects or increases in clinical events, even in the four elite athletes with SARS-CoV-2 associated myocardial involvement.
- COVID-19
- Inflammation
- Myocarditis
- Magnetic Resonance Imaging
Data availability statement
Data are available on reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Short-term follow-up and cross-sectional studies have shown a low prevalence (3%–5%) of myocardial abnormalities, including infrequent cardiac adverse events in competitive athletest infected with SARS-CoV-2.
WHAT THIS STUDY ADDS
This prospective, controlled study demonstrates the safety of resuming elite-level sports in athletes infected with SARS-CoV-2. During 2-year follow-up, elite-level sports did not lead to detrimental cardiac effects or an increase in cardiac events, even in four elite athletes with SARS-CoV-2 associated myocardial involvement. None of the athletes infected with SARS-CoV-2 ended their professional sports careers due to SARS-CoV-2.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Our study provides longer-term reassuring insights regarding cardiac safety in the context of elite-level sports and SARS-CoV-2 and suggests that a liberal but personalised approach may be warranted for athletes infected with SARS-CoV-2 who wish to return to (elite-level) sports.
Introduction
Active myocarditis is considered an absolute contraindication for participation in sports and exercise.1 As SARS-CoV-2 has been associated with myocardial involvement in up to 5% of young competitive athletes,2 the longer-term effects of sports after SARS-CoV-2 infection are of particular relevance and interest. While studies investigating the effects of exercise during active myocarditis in humans are lacking due to ethical reasons, mice models have shown strong deleterious cardiac effects such as adverse ventricular remodelling and an increase in ventricular tachyarrhythmias and mortality.3 Consequently, athletes diagnosed with or suspected of active myocarditis are advised to refrain from sports for 3–6 months,1 which can significantly impact an athlete’s professional career.
Screening strategies for myocardial involvement following SARS-CoV-2 infection have been subject to intense scrutiny. The majority of these mainly cross-sectional and opportunistic studies have focused on the prevalence of cardiac abnormalities and the implementation of return-to-sports (RTS) screening protocols.4–11 Prospective studies investigating longer-term outcomes are lacking. Additionally, there is a knowledge gap concerning the potential association between SARS-CoV-2-associated cardiac abnormalities and sports- and exercise, particularly in relation to adverse cardiac remodelling and ventricular arrhythmias. Elite athletes, whose cardiac integrity is a prerequisite for maintaining excellence in performance and who are potentially prone to the most deleterious exercise-induced cardiac effects, constitute a group of special interest when investigating this.
We therefore aimed to prospectively investigate the clinical course of SARS-CoV-2 and RTS in elite athletes over time. Moreover, we determined the prevalence of SARS-CoV-2 associated myocardial sequelae. Lastly, in athletes with SARS-CoV-2 associated cardiac abnormalities who returned to sports, we assessed long-term cardiac remodelling and monitored ventricular arrhythmias.
Methods
Study design
We performed a prospective analysis of elite athletes included in the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort (NL9328). The methods of ELITE have been described elsewhere.12 In short, ELITE is a prospective, multicentre longitudinal cohort study that collects standardised periodic cardiovascular screening data of elite athletes in The Netherlands and is ongoing since April 2019. Athletes and the public are actively involved, as the Dutch National Olympic Committee & National Sports Federation is a coinitiator of this study. From March 2020, elite athletes with a confirmed SARS-CoV-2 infection underwent (additional) standardised cardiovascular screening after infection and were simultaneously included in a subcohort of the ELITE study titled ‘COVID-19 Myocardial Manifestations in Intensive Top-level sports and exercise’ (COMMIT). Athletes were approached by their personal or team/sports physician to participate in the ELITE study and/or COMMIT subcohort; all included athletes provided written informed consent. Athletes with a history of cardiovascular disease prior to SARS-CoV-2 infection were excluded.
Study population
All included elite athletes (ie, Olympians, Paralympians and/or professional athletes) are 16 years or older and exercise more than 10 hours per week with an emphasis on competition and performance.1 Athletes included before the onset of the COVID-19 pandemic and athletes who self-reported not to have been infected with SARS-CoV-2, with additional confirmation by a negative serology test, were considered as non-infected controls. SARS-CoV-2 infection was confirmed by either a positive PCR or a positive serology test in unvaccinated individuals.
Data collection
We collected cardiovascular screening and clinical follow-up data of all included elite athletes, including demographic characteristics such as age, sex, ethnicity, body surface area (BSA), type of athletic discipline and time (years) participating on a professional athlete level. Cardiovascular screening consisted of electrocardiography, laboratory assessment (high-sensitive troponin T (HsTnT), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), creatine phosphokinase-MB (CKMB), inflammatory markers (C reactive protein (CRP) and leucocytes) and cardiovascular MRI (CMR). Post-infection cardiovascular screening was performed according to the standardised ELITE screenings protocol and was performed at the Amsterdam University Medical Centres or the Erasmus University Medical Centre. SARS-CoV-2 symptom severity was recorded, classified as: (1) asymptomatic (no symptoms during infection); (2) cardiovascular symptoms (dyspnoea, chest pain, (near-)syncope and palpitations); and (3) symptomatic; no cardiovascular symptoms (eg, gastrointestinal, respiratory symptoms and fever). The date of SARS-CoV-2 onset was defined as the date of positive PCR, or in case of positive serology, the date of onset of symptoms. The interval between infection and cardiovascular assessment was calculated based on the date of SARS-CoV-2 infection onset.
Electrocardiogram
Twelve-lead resting supine ECGs were independently assessed by two investigators, of which one expert in (sports) cardiology, according to the international recommendations for electrocardiographic interpretation in athletes by the European Society of Cardiology (ESC), and accordingly classified as normal, borderline or abnormal.12 13
Cardiovascular magnetic resonance
Contrast-enhanced CMR was performed on 1.5-Tesla and 3.0-Tesla MRI scanners (Siemens Avanto Fit 1.5T, Philips Elition 3.0T or GE Healthcare SGINA Artist 1.5T) with ECG gating and a dedicated body coil for cardiac measurements. The CMR protocol included cine imaging of long-axis and short-axis views, native T1 modified look locker inversion recovery sequence mapping short-axis slices and late gadolium enhancement (LGE) images.
CMR data analysis was performed in Circle Cardiovascular Imaging (cvi42 V.5.12.4, Calgary, Alberta, Canada) by a core lab consisting of ELITE investigators (SMV, JCvH, JJND and MAvD), with dedicated supervision of expert radiologists and imaging cardiologists (SMB, AvR, RNP, MG and AH) with extensive experience in quantitative analysis of athlete CMR data. Epicardial and endocardial end-systolic and diastolic contours of both ventricles were automatically determined using an artificial intelligence integrated tool and manually corrected if needed. Short-axis cine images were used to determine left and right ventricular (LV/RV) end-diastolic and end-systolic volumes (including papillary muscle and trabecularisation) (EDV/ESV), stroke volumes and ejection fractions and LV mass (LVM) (excluding papillary muscle and trabecularisation). All volumes were indexed for BSA according to the Mosteller formula. The remodelling index (LVM/LVEDV) and balanced remodelling ratio (LVEDV/RVEDV) were determined. The presence of LGE (including pericardial LGE) was determined on phase-sensitive inversion recovery images through visual identification and if visually present quantified using a threshold of 6 SD above normal myocardium signal intensity. Hinge-point LGE was not considered indicative of SARS-CoV-2 myocardial involvement. Native T1 relaxation times were measured in all acquired slices (basal, midventricular and apical) using a 15% margin of epicardial and endocardial contours. All CMRs were clinically assessed according to local protocol and normal values. Due to interscanner differences in normal T1 relaxation times, only the T1 mapping results from the Amsterdam UMC performed on a Siemens Avanto Fit 1.5T MRI machine were included in the tables and analyses. T1 slices with poor quality (ie, due to movement or artefacts) were excluded from analyses.
Follow-up
When the CMR of athletes infected with SARS-CoV-2 demonstrated cardiac abnormalities, follow-up CMR was performed according to clinical judgement, with a preference for repeat evaluations at 3, 6 and 9 months post-infection. Additionally, intensive rhythm monitoring was performed using multiple conventional 24-hour Holters and 8-day continuous 1-lead monitoring (Philips Biosensor) and cardiopulmonary exercise tests. Moreover, in all athletes exposed to SARS-CoV-2, we collected data on cardiac symptoms and/or events (dyspnoea, chest pain, (near-)syncope and palpitations), and return to sports, including current level of sports participation, through a combination of the ongoing data collection of ELITE, the athlete management system and by outcome data collection performed by their dedicated personal and team (sports) physicians.
Statistical methods
Categorical values are presented as numbers and percentages; continuous variables are presented as mean and SD or median with IQR, as appropriate. The normality of distribution was visually analysed with histograms and calculated using Shapiro-Wilk’s test. For the cross-sectional analyses comparing athletes infected with SARS-CoV-2 with athletes who were not infected, we compared ECG data, cardiac biomarkers, inflammatory markers and CMR parameters using unpaired t-tests, Mann-Whitney U tests, χ2 tests or Fisher’s exact tests, as appropriate. For the subgroup eligible for analyses using pre- and post-infection data, we applied paired t-tests, Wilcoxon signed-rank tests or McNemar tests. The alpha level was set at 0.05. Athletes with missing data for a specific variable were only excluded from the analysis of that specific variable. However, they were included in other analyses conducted. Statistical analyses were performed using R (Rstudio V.2021.09.0).
Results
A total of 259 elite athletes were included between May 2019 and November 2022. In total, 123 elite athletes recovered from a SARS-CoV-2 infection, and 136 were not exposed to SARS-CoV-2 (self-reported to be negative and confirmed with a negative serology test (n=107), or included in ELITE before the onset of the COVID-19 pandemic (n=29) (table 1). Athletes infected with SARS-CoV-2 were similar in sex distribution (33% vs 45% female athletes) compared with elite athlete controls. However, athletes infected with SARS-CoV-2 were younger (25±6 vs 27±7 years, p=0.014), had a higher BSA (2.0±0.2 vs 1.9±0.2 m2, p=0.006) and fewer athletes were of Caucasian ethnicity (80% vs 99%, p=<0.001). A higher percentage of athletes infected with SARS-CoV-2 participated in football (30% vs 7%, p<0.001) and had fewer professional athlete years (11±6 vs 13±7, p=<0.001). Of all athletes infected with SARS-CoV-2, 19% were asymptomatic, 9% had cardiovascular symptoms (palpitations 6%, chest pain 9%) and 72% had respiratory symptoms (no cardiovascular symptoms). The mean symptom duration was 10±15 days. Follow-up data were collected up to a mean of 26.7 (±5.7) months in elite athletes who recovered from SARS-CoV-2 infection. No athletes were lost to follow-up; missing data are presented in the online supplemental material.
Supplemental material
Population characteristics of athletes infected with SARS-CoV-2 compared with elite athlete controls
Cross-sectional cardiovascular assessment
We compared 123 elite athletes exposed to SARS-CoV-2 with 136 elite athlete controls. The mean time interval between the onset of SARS-CoV-2 infection and cardiovascular assessment was 3.9 (±2.9) months. Results of ECG, laboratory and CMR findings in elite athletes exposed to SARS-CoV-2 compared with elite athlete controls are presented in table 2 and the online supplemental material.
Cross-sectional assessment of ECG, laboratory and CMR findings in elite athletes exposed to SARS-CoV-2 versus non-exposed elite athlete controls
Electrocardiography and laboratory assessment
Elite athletes exposed to SARS-CoV-2 infection showed a higher resting heart rate (57 (51–66) vs 52 (46–57) bpm, p<0.001) compared with controls. There were no differences in ECG categories (normal 82% vs 87%, borderline 9% vs 10%, and abnormal 5% vs 2%). Detailed ECG assessments can be found in the online supplemental material. Furthermore, there was no difference in the amount of athletes with elevated cardiac biomarkers (hsTnT, NT-proBNP and CK-MB) and inflammatory markers (CRP and leucocytes), compared with controls.
Cardiovascular magnetic resonance imaging
The CMR findings in elite athletes exposed to SARS-CoV-2 revealed no significant differences in mean LVEDV (116±18 vs 120±19 mL/m2), LVESV (51±10 vs 53±11 mL/m2), LVEF (56±5 vs 56±5%), RVEDV (117±18 vs 121±20 mL/m2), RVESV (54±10 vs 55±11 mL/m2) and RVEF (54±5 vs 55±5%) when compared to non-exposed elite athlete controls. Similarly, there were no differences in cardiac remodelling ratios: LVM/LVEDV (0.5±0.1 vs 0.5±0.1) and LVEDV/RVEDV (1.0±0.1 vs 1.0±0.1). Moreover, infected athletes did not show higher native T1 relaxation times (962±22 vs 961±24 ms). Four (3%) athletes exposed to SARS-CoV-2 demonstrated pathological non-ischaemic patterns of myocardial LGE (≤20% of total LV mass); none of the non-exposed athletes demonstrated pathological LGE patterns. All four athletes with a pathological LGE pattern had normal cardiac function and volumetric parameters according to current athlete CMR reference ranges.14 No pre-infection CMRs were available for the athletes with pathological LGE.
Prospective CMR assessment
CMR assessment before and after SARS-CoV-2 infection was available in 23 (19%) elite athletes (mean age 26.8±5, 44% women) (table 3 and online supplemental table 2). The mean time between pre-infection and post-infection CMR was 16±7 months and between SARS-CoV-2 onset and post-infection CMR 2±2 months. Comparing pre-infection to post-infection CMR, we only observed a difference in BSA-indexed LVM (66±16 vs 55±15 g/m2, p=0.018) and LVM/LVEDV cardiac remodelling ratio (0.6±0.1 vs 0.5±0.9, p=0.001). The post-SARS-CoV-2 infection CMR demonstrated no change in volumetric (LVEDV (116±16 vs 121±15 mL/m2), LVESV (51±11 vs 54±8 mL/m2), RVEDV (120±18 vs 120±15 mL/m2), RVESV (56±13 vs 54±9 mL/m2)) and functional (LVEF (56±5 vs 55±5%), RVEF (54±6 vs 55±5%)) CMR parameters. Moreover, there were no changes in native T1 relaxation times and/or the presence of pathological LGE patterns over time.
Prospective assessment of pre-SARS-CoV-2 and post-SARS-CoV-2 infection ECG, laboratory and CMR findings within the same elite athlete
Return to sports and follow-up
SARS-CoV-2 exposed athletes
Of the 123 elite athletes infected with SARS-CoV-2, four (3%) had distinct pathological LGE patterns with variable evolution over time (figure 1), without complex ventricular tachycardias ((non-) sustained ventricular tachycardia) and no increase in PVC burden. Their clinical course is described in table 4 and in the online supplemental material. The remaining 119 athletes (97%) demonstrated CMR function and volumetric parameters within normal ranges for athletes,14 normal T1 relaxation times and no pathological LGE. None of the infected athletes reported cardiovascular symptoms or events after a mean follow-up of 26.7 (±5.8) months. In total, 96% (118) made a complete return to elite-level sports. Five (4%) athletes terminated their professional sports careers due to non-SARS-CoV-2 related considerations.
Individual case description over time of athletes with myocardial involvement after infection with SARS-CoV-2
Short-axis late gadolinium enhancement (LGE) images of individual sequential CMRs performed in four athletes with SARS-CoV-2 associated pericardial/myocardial LGE demonstrated with an arrow including time interval between infection with SARS-CoV-2 and CMR. CMR, cardiovascular MRI.
Discussion
This elite athlete, extreme phenotyping study demonstrates that infection with SARS-CoV-2 is not associated with detrimental effects on cardiac function and ventricular volumes after return to elite sports, both when investigated cross-sectionally with controls (non-infected athletes) and prospectively, comparing pre-infection and post-infection CMR in individual athletes. There was a low prevalence (3%) of perimyocardial involvement, with a variable clinical presentation and clinical course over time, ranging from complete resolution of LGE to persistent LGE without other signs of inflammation. We found no signs of detrimental morphological changes or increases in ventricular arrhythmias in elite athletes with SARS-CoV-2 cardiac sequelae, even after the resumption of elite competitive sports. Moreover, during more than 2 years of follow-up, there were no new SARS-CoV-2 related (de novo) cardiac complaints or adverse cardiac events in athletes with and without clear SARS-CoV-2 associated abnormalities at the initial post-infection examination.
While elite athletes might be protected from COVID-19 complications due to their exceptional fitness, they also constitute a unique extreme phenotyping model to investigate the role of exercise as a second hit or trigger for adverse cardiac remodelling after SARS-CoV-2 infection.15–17 Our findings therefore add to previous studies, which have mainly been cross-sectional, survey-based and performed on collegiate athletes. Our rate of post-SARS-CoV-2 myocardial injury was low compared with non-athletic populations and in line with previous findings.2 Reassuringly, we observed only a decrease in the left-venticular remodelling index in individuals with pre- and post-SARS-CoV-2 CMR measurements, which potentially illustrates the impact of detraining during the COVID-19 pandemic, and no other detrimental cardiac changes in volumes or function.
Short-term follow-up studies have shown an absence or a low prevalence of cardiac adverse events in athletes with and without cardiac involvement after infection with SARS-CoV-2.9 18 19 Our study extends on these findings with long-term follow-up during a period of more than 2 years. Although the group of athletes with SARS-CoV-2 related damage was small, and caution is warranted when deriving conclusions from this data, it is reassuring that we found no increase in ventricular arrhythmias or adverse cardiac remodelling, even after resumption of elite-level sports. Most importantly, the cessation of professional athletic careers, irrespective of the presence or absence of cardiac sequelae, was not associated with a prior SARS-CoV-2 infection, during more than 2 years of follow-up.
Clinical implications
Standardised CMR-based screening following infection with SARS-CoV-2 provides valuable insights into myocardial damage, with a low but non-negligible detection rate, consistent with previous studies. Importantly, successful RTS can be achievable for elite athletes, even in the presence of myocardial abnormalities. Moreover, counselling during return-to-sports trajectories,20 21 in addition to consensus return-to-play protocols22 23 is important in the RTS process. These findings contribute to the development of evidence-based protocols for safe RTS after SARS-CoV-2 infection, which is of benefit for all athletes, regardless of level.
Strengths and limitations
This study has several strengths. First, earlier studies were mainly performed on collegiate athletes and were cross-sectional in nature. While not the first study to report follow-up in athletes, this is the first study to prospectively investigate a rigorously defined and phenotyped cohort of elite athletes with homogeneous high-level training regimens. Second, the study included an appropriately selected control group including athletes enrolled prior to the pandemic. The absence of an appropriate control group has been an important limitation in numerous COVID-19 studies. Third, we conducted both cross-sectional controlled comparisons and prospective analyses using pre-SARS-CoV-2 and post-SARS-CoV-2 infection CMR measurements. Fourth, consecutive CMR studies were performed in cases with SARS-CoV-2 cardiac abnormalities to investigate potential adverse cardiac remodelling and/or recovery of the abnormalities on resumption of elite-level sport. Finally, this study performed intensive arrhythmia monitoring in elite athletes with SARS-CoV-2 associated cardiac sequelae, not only during exercise testing but also during general team trainings on the field.
Some aspects of our study warrant consideration. First, it was not possible to determine the exact date of SARS-CoV-2 infection in unvaccinated asymptomatic athletes who tested positive with an antibody test. Therefore, the causality of SARS-CoV-2 associated abnormalities cannot be ascertained, potentially leading to attribution bias. However, extensive history-taking revealed no other possible explanations. Second, as only four athletes were found with SARS-CoV-2 related cardiac abnormalities, clinical decision making based on this modest number should adhere to current international guidelines. Follow-up studies and case series in such athletes are urgently needed. Finally, we performed no arrhythmia monitoring in the athletes infected with SARS-CoV-2 without cardiac sequelae. These athletes remained however under the supervision of experienced sports physicians, trainers and other professionals, and commonly use photo-plethysmography, with no reports of new abnormalities during follow-up. Although an increase in subclinical ventricular arrhythmias cannot be excluded, the presence thereof remains unlikely.
Conclusion
Resumption of elite-level competitive sports after a SARS-CoV-2 infection is safe and feasible, even in the small group (3%) of athletes with SARS-CoV-2 related myocardial sequelae. Our study shows that, in elite athletes, cessation of professional sports careers was not associated with SARS-CoV-2. We observed no interaction between high-intensity exercise, cardiac remodelling and SARS-CoV-2 during cross-sectional controlled or prospective analysis. During more than 2 years of follow-up, no cardiac symptoms or adverse cardiac events were reported by the included athletes after resuming elite-level sports.
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
ELITE has been approved by the Amsterdam UMC Medical Ethics Committee (NL71682.018.19). Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We gratefully acknowledge the contribution of the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) consortium, all athletes and our sports physicians collaborators, in particular Niels Wijne and Maikel van Wijk.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors HTJ conceived the main conceptual idea and acted as guarantor. JCvH, JJND, LVW and AH contributed to the design of the manuscript. JCvH wrote the manuscript with input from all authors in consultation with JJND, SMV, LVW, MAvD, MG, SMB, RNP, AvR, AH, MHM and HTJ. All authors discussed the findings and commented on the manuscript. YMP and AAMW supervised the project.
Funding HTJ has received funding for ELITE from Amsterdam Movement Sciences (P1A210AMC2018) and Dutch National Olympic Committee & National Sports Federation (JZ/18.0166/swt). HTJ has received funding for COMMIT from the Netherlands Heart Foundation (01-001-2020-T079) and the Netherlands Organization for Health Research and Development (ZonMw), grant number 10430102110006 DEFENCE.
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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