Our systematic review addressing cardiac abnormalities in athletes recovered from SARS-CoV-2 infection found marked heterogeneity in investigations, study populations and methodology. The majority of abnormal pericardial/myocardial findings were reported by studies performing CMR as part of their investigations. Overall, myocardial abnormalities on CMR such as myocardial LGE and confirmed myocarditis (LLC) was reported in 0%–15% of cases. Pericardial abnormalities such as PE and pericardial LGE were reported in 0%–57% (CMR) of cases. In the total population, myocarditis was reported on echocardiography and/or CMR in 0%–15%, PE in 8%–58% and LGE in 0%–46%. Importantly, our findings also demonstrate that lower quality studies tended to report considerably higher rates of abnormalities (38%–42%). Studies with higher quality assessment scores showed a somewhat greater agreement in proportions of athletes with LGE (0%–5%) after SARS-CoV-2 infection. As such, our review highlights that emergent, small, low-quality studies should be interpreted with caution and a need for prospective, large athlete cohort studies with a low risk of bias.
Clinical implications
This review demonstrates that the incidence of post-SARS-CoV-2 myocardial abnormalities detected on CMR is low and that CMR is the most sensitive diagnostic modality to detect myocardial abnormalities in athletes. As such, using CMR as a screening modality to detect potential SARS-CoV-2 myocardial abnormalities warrants further investigation. Additionally, while no studies systematically performed extensive arrhythmia monitoring in individuals with clear myocardial abnormalities, these studies also report no clear cases of SCA/SCD. Therefore, until prospective studies have been published, systematic (arrhythmia) monitoring is recommended in athletes with myocardial abnormalities after SARS-CoV-2. Finally, and perhaps most relevant for sports physicians directly involved in RTS in athletes, troponin screenings outside of specific clinical contexts (ie, cardiac complaints or other diagnostic abnormalities) should not occupy a central place in return-to-play strategies.
FU CMR was reported in only one study (Daniels et al) and demonstrated complete reversibility in approximately 40% of individuals diagnosed with myocarditis. Two studies (Gervasi et al and Cavigli et al) investigated arrhythmia outcomes, with only a single athlete demonstrating couplets at peak effort and in early recovery; this athlete was consequently diagnosed with myopericarditis. One study reported a single instance of resuscitated SCA likely unrelated to COVID-19, with no abnormalities on a prior CMR performed after SARS-CoV-2 infection. No study reported a clear relationship between elevated troponin levels and cardiac abnormalities on imaging investigations. Based on the currently available data, the short-term risk for post-COVID-19 SCA/SCD due to arrhythmias caused by myocardial inflammation appears to be poorly investigated, yet reported numbers are low, and the propensity for SARS-CoV-2 pericardial and myocardial involvement variable.
Although physical activity is thought to negatively influence prognosis in athletes with pericarditis and myocarditis,5 the rate of myocarditis in athletes after SARS-CoV-2 infection appears low. Overall, athletes were asymptomatic (36%) or had mild symptoms (59%), which may be reflected in the low rates of myocardial injury. FU data in athletes who continue to perform sports after SARS-CoV-2 infection is needed to further elucidate a potential interaction between physical activity and myocardial involvement.
All CMR studies were cross-sectional or retrospective, and only a single study with a small sample size (n=18) performed comparative echocardiography analyses with pre- SARS-CoV-2 infection imaging. While it seems plausible that athletes who fulfil the LLC for myocarditis shortly after infection with SARS-CoV-2 have SARS-CoV-2 myocardial involvement, a recent study in healthcare workers has questioned whether such abnormalities are more common in individuals recovered from SARS-CoV-2 infection when compared with an adequate control group.36 Therefore, caution is advised before attributing (isolated) cardiac abnormalities to SARS-CoV-2. Ideally, to rule out pre-existent abnormalities due to other causes, imaging studies in athletes with pre-existing CMRs should be performed, preferably in well-defined groups as opposed to all comers in imaging centres, with core-lab assessment of all imaging studies. Furthermore, considering the potential reversibility of pericardial/myocardial abnormalities reported by Daniels et al, the extent, and time course and long-term reversibility has yet determined.
Echocardiography findings in our study population did not demonstrate a high prevalence of major cardiac abnormalities, or significant differences compared with in-study controls. Of note, only Brito et al reported a high prevalence of pericardial LGE in athletes. Surprisingly, after multimodality adjudication, they demonstrated an association between GLS <−16% on echocardiography and pericardial/myocardial abnormalities on CMR. First, as GLS is mainly a myocardial parameter, this association hints at possible pericardial/myocardial involvement, not detectable on CMR. Second, while GLS could potentially be a promising tool to identify COVID-19 associated pericardial/myocardial involvement, this finding has not yet been replicated in other studies, and hence such a strategy should not be implemented in routine care for post-COVID-19 athletes. Second, Martinez et al35 reported four (of six) cases with abnormal echocardiography (with varying findings) and confirmed pericarditis/myocarditis on CMR. However, they only performed CMRs in athletes with a suspicion of pericardial/myocardial involvement after return-to-play screening, and it is unclear whether athletes without conventional screening abnormalities also had CMR abnormalities. Therefore, according to our findings, screening echocardiography should be used with caution to perform rule-outs for subclinical myocarditis.
Several groups have speculated on causes for SCA/SCD related to COVID-19, such as possible proarrhythmic genetic predisposition or comorbidities that potentially increase the risk of drug-induced and hypoxia-induced ventricular arrhythmias/SCD.37 38 Yet, while the studies identified by our systematic review extensively investigated and reported myocardial abnormalities as found using CMR, none of these studies performed a structured investigation of potential arrhythmias. One study (Gervasi et al) found no clinically important arrhythmias in 18 football players. However, in addition to the small sample size, this study did not include CMR to document myocardial abnormalities. One study (Moulson et al) reported a resuscitated SCA (likely unrelated to SARS-CoV-2) with no abnormal findings on prior CMR after SARS-CoV-2 infection. Hence, these findings cannot readily be extrapolated to athletes with potential or suspected myocardial involvement after COVID-19.
The majority of the studies included in our systematic review determined troponin levels after recovery from COVID-19. Of import, no single paper reported a statistically significant association between elevated serum troponin levels and CMR or echocardiography abnormalities. Therefore, the use of serum troponin after recovery to predict SARS-CoV-2 myocardial involvement remains questionable, with the potential for both false negative and false positive outcomes. According to our findings, troponin testing should not occupy a central place in return-to-play algorithms, and only be applied in appropriate (expert) clinical settings.
Strengths and limitations
There are several strengths to our study. First, we performed a systematic search through multiple databases, including articles ahead-of-print. Second, data extraction was rigorously performed to report each diagnostic finding. Third, we were able to stratify and weight main findings according to athlete level and recovery location (in-hospital or/and at home). Finally, all studies underwent extensive quality assessment, enabling us to stratify central findings according to study quality.
A number of aspects of our systematic review warrant consideration. First, the majority of the studies included in our review were found to have risk of bias. However, the scarcity of data on this topic in an emerging pandemic makes this a currently unavoidable bias. Second, we did not include case reports in our systematic review, as these included non-athletes with high rates of comorbidities, and because such reports have an intrinsic selection bias. Third, the data across the identified studies was heterogeneous, which limits generalisability. Fourth, the time interval between symptoms onset to cardiac imaging was too variable to allow for a cumulative analysis. Finally, we focused on late complications including late arrhythmias (ie, post-COVID-19) and not on the arrhythmia burden during an active SARS-CoV-2 infection.