Clinical spectrum of COVID-19 complications in young adults: combined analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry and the Outcomes Registry for Cardiac Conditions in Athletes.

BACKGROUND: While young adults 18-24 years old bear a significant proportion of COVID-19 diagnoses, the risk factors for hospitalisation and severe COVID-19 complications in this population are poorly understood. OBJECTIVE: The objective of this study was to identify risk factors for hospitalisation and other COVID-19 complications across the health spectrum of young adults diagnosed with COVID-19 infection. STUDY DESIGN: Retrospective cohort study. PARTICIPANTS: Young adults (aged 18-24) with confirmed COVID-19 infection from the American Heart Association (AHA) COVID-19 Cardiovascular Disease Registry of hospitalised patients and the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study of collegiate athletes. The AHA registry included 636 young adults from 152 hospitals. The ORCCA registry consisted of 3653 competitive college athletes from 42 colleges and universities. INTERVENTION: None (exposure to COVID-19). PRIMARY AND SECONDARY OUTCOME MEASURES: Main outcomes included hospitalisation, death, major adverse cardiovascular events (MACE) and other severe clinical events. RESULTS: In comparison to the ORCCA registry, patients in the AHA registry were more likely to be female (59% vs 33%); had higher average body mass index (BMI) (32.4 vs 25.6); and had increased prevalence of diabetes (10% vs 0.4%), hypertension (7% vs 0.6%), chronic kidney disease (2% vs 0%) and asthma (14% vs 8%), all with p<0.01. There were eight (2%) deaths in the AHA hospitalised registry compared with zero in the ORCCA cohort. BMI was a statistically significant predictor of death in the hospitalised cohort (OR 1.05, 95% CI 1.00, 1.10). No significant predictors of MACE or other severe clinical events were identified. CONCLUSIONS: The risk of cardiac events in young adults aged 18-24 diagnosed with COVID-19 infection is low. Patients who were hospitalised (AHA registry) were more likely to have pre-existing medical comorbidities and higher BMI than healthy collegiate athletes (ORCCA registry). Once hospitalised, elevated BMI is associated with increased mortality although other drivers of MACE and other severe clinical events remain unclear.

The Cardiac Effects of COVID-19 on Young Competitive Athletes: Results from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA).

The Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study is a large-scale prospective investigation evaluating the cardiovascular effects and outcomes of SARS-CoV-2 infection on young competitive athletes. This review provides an overview of the key results from the ORCCA study. Results from the ORCCA study have provided important insights into the clinical impact of SARS-CoV-2 infection on the cardiovascular health of young competitive athletes and informed contemporary screening and return to sport practices. Key results include defining a low prevalence of both cardiac involvement and adverse cardiovascular outcomes after SARS-CoV-2 infection and evaluating the utility of a return-to-play cardiac evaluation. Future aims of the ORCCA study include the longer-term evaluation of cardiovascular outcomes among athletes post-SARS-CoV-2 infection and the transition to investigating outcomes in young athletes with potentially high-risk genetic or structural cardiac diagnoses.

Cardiac Troponin Testing as a Component of Return to Play Cardiac Screening in Young Competitive Athletes Following SARS-CoV-2 Infection.

Background Initial protocols for return to play cardiac testing in young competitive athletes following SARS-CoV-2 infection recommended cardiac troponin (cTn) to screen for cardiac involvement. This study aimed to define the diagnostic yield of cTn in athletes undergoing cardiovascular testing following SARS-CoV-2 infection. Methods and Results This prospective, observational cohort study from ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) included collegiate athletes who underwent cTn testing as a component of return to play protocols following SARS-CoV-2 infection. The cTn values were stratified as undetectable, detectable but within normal limits, and abnormal (>99% percentile). The presence of probable or definite SARS-CoV-2 myocardial involvement was compared between those with normal versus abnormal cTn levels. A total of 3184/3685 (86%) athletes in the ORCCA database met the inclusion criteria for this study (age 20±1 years, 32% female athletes, 28% Black race). The median time from SARS-CoV-2 diagnosis to cTn testing was 13 days (interquartile range, 11, 18 days). The cTn levels were undetectable in 2942 athletes (92%), detectable but within normal limits in 210 athletes (7%), and abnormal in 32 athletes (1%). Of the 32 athletes with abnormal cTn testing, 19/32 (59%) underwent cardiac magnetic resonance imaging, 30/32 (94%) underwent transthoracic echocardiography, and 1/32 (3%) did not have cardiac imaging. One athlete with abnormal troponin met the criteria for definite or probable SARS-CoV-2 myocardial involvement. In the total cohort, 21/3184 (0.7%) had SARS-CoV-2 myocardial involvement, among whom 20/21 (95%) had normal troponin testing. Conclusions Abnormal cTn during routine return to play cardiac screening among competitive athletes following SARS-CoV-2 infection appears to have limited diagnostic utility.

Diagnostic evaluation and cardiopulmonary exercise test findings in young athletes with persistent symptoms following COVID-19.

OBJECTIVES: Persistent or late-onset cardiopulmonary symptoms following COVID-19 may occur in athletes despite a benign initial course. We examined the yield of cardiac evaluation, including cardiopulmonary exercise testing (CPET), in athletes with cardiopulmonary symptoms after COVID-19, compared CPETs in these athletes and those without COVID-19 and evaluated longitudinal changes in CPET with improvement in symptoms. METHODS: This prospective cohort study evaluated young (18-35 years old) athletes referred for cardiopulmonary symptoms that were present>28 days from COVID-19 diagnosis. CPET findings in post-COVID athletes were compared with a matched reference group of healthy athletes without COVID-19. Post-COVID athletes underwent repeat CPET between 3 and 6 months after initial evaluation. RESULTS: Twenty-one consecutive post-COVID athletes with cardiopulmonary symptoms (21.9±3.9 years old, 43% female) were evaluated 3.0±2.1 months after diagnosis. No athlete had active inflammatory heart disease. CPET reproduced presenting symptoms in 86%. Compared with reference athletes (n=42), there was similar peak VO2 but a higher prevalence of abnormal spirometry (42%) and low breathing reserve (42%). Thirteen athletes (62%) completed longitudinal follow-up (4.8±1.9 months). The majority (69%) had reduction in cardiopulmonary symptoms, accompanied by improvement in peak VO2 and oxygen pulse, and reduction in resting and peak heart rate (all p<0.05). CONCLUSION: Despite a high burden of cardiopulmonary symptoms after COVID-19, no athlete had active inflammatory heart disease. CPET was clinically useful to reproduce symptoms with either normal testing or identification of abnormal spirometry as a potential therapeutic target. Improvement in post-COVID symptoms was accompanied by improvements in CPET parameters.

Plasma Proteomics of COVID-19-Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics.

To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFß signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

Impact of the COVID-19 pandemic on perceived cardiorespiratory fitness in athlete patients.

INTRODUCTION: Cardiorespiratory fitness (CRF), as one of the most potent prognostic factors in medicine, is followed longitudinally to guide clinical management. Coronavirus disease 2019 (COVID-19) pandemic-related changes in lifestyle stand to influence CRF. OBJECTIVE: To assess the influence of the pandemic on perceived CRF in athlete patients and evaluate how perceived CRF change was related to demographics, pre-pandemic measured CRF, and current physical activity (PA). DESIGN: Prospective cohort study, utilizing electronic survey. SETTING: Tertiary care sports cardiology clinical practice. PARTICIPANTS: Adult athlete patients without COVID-19 with pre-pandemic measured CRF using cardiopulmonary exercise testing. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Perceived change in CRF since pandemic onset; association between perceived CRF change and demographics, PA, health status, and pre-pandemic measured CRF assessed via analysis of variance (ANOVA). RESULTS: Among 62 participants (male: 71%, 50.1 ± 12.1 years old), 40% (25/62) reported no change and 32% (20/62) reported an increase in perceived CRF since pandemic onset. Among the 27% (17/62) who reported a decrease in perceived CRF, in most (12/17), this was characterized as only mild. Demographics and pre-pandemic measured CRF did not differ across groups of perceived CRF change. Participants with a moderate or greater decrease in perceived CRF regarded their overall health (via Euro Quality of Life Visual Analogue Scale) as worse than other groups (ANOVA, p = .001). Although total PA was similar across groups, those who had improvement in perceived CRF reported higher levels of moderate intensity PA (ANOVA, p = .008). CONCLUSIONS: The majority of participants perceived that they had maintained or improved CRF over the pandemic. Findings from this study suggest that a reduction in perceived CRF from pre-pandemic values in athletic patients in clinical practice may not result from population-wide pandemic changes in lifestyle. Worse health status and lower levels of moderate intensity PA were associated with perceived reduction in CRF over the pandemic in athlete patients.

Electrocardiographic findings in young competitive athletes during acute SARS-CoV-2 infection.

Initial guidelines recommended a 12-lead electrocardiogram (ECG) in young competitive athletes following SARS-CoV-2 infection to screen for myocarditis. However, no data are available that detail ECG findings before and after SARS-CoV-2 infection in young athletes without clinical or imaging evidence of overt myocarditis. This study applied the International Criteria for ECG interpretation in a cohort of 378 collegiate athletes to compare ECG findings at baseline and during the acute phase of SARS-CoV-2 infection. Our results suggest that ECG changes can occur in the absence of definitive SARS-CoV-2 cardiac involvement in young competitive athletes.

Prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms following SARS-CoV-2 infection in 3597 collegiate athletes: a study from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA).

OBJECTIVE: To assess the prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms in young competitive athletes following SARS-CoV-2 infection. METHODS: This observational cohort study from the Outcomes Registry for Cardiac Conditions in Athletes included 3597 US collegiate athletes after SARS-CoV-2 infection. Clinical characteristics, advanced diagnostic testing and SARS-CoV-2-associated sequelae were compared between athletes with persistent symptoms >3 weeks, exertional symptoms on return to exercise and those without persistent or exertional symptoms. RESULTS: Among 3597 athletes (mean age 20 years (SD, 1 year), 34% female), data on persistent and exertional symptoms were reported in 3529 and 3393 athletes, respectively. Persistent symptoms >3 weeks were present in 44/3529 (1.2%) athletes with 2/3529 (0.06%) reporting symptoms >12 weeks. Exertional cardiopulmonary symptoms were present in 137/3393 (4.0%) athletes. Clinical evaluation and diagnostic testing led to the diagnosis of SARS-CoV-2-associated sequelae in 12/137 (8.8%) athletes with exertional symptoms (five cardiac involvement, two pneumonia, two inappropriate sinus tachycardia, two postural orthostatic tachycardia syndrome and one pleural effusion). No SARS-CoV-2-associated sequelae were identified in athletes with isolated persistent symptoms. Of athletes with chest pain on return to exercise who underwent cardiac MRI (CMR), 5/24 (20.8%) had probable or definite cardiac involvement. In contrast, no athlete with exertional symptoms without chest pain who underwent CMR (0/20) was diagnosed with probable or definite SARS-CoV-2 cardiac involvement. CONCLUSION: Collegiate athletes with SARS-CoV-2 infection have a low prevalence of persistent or exertional symptoms on return to exercise. Exertional cardiopulmonary symptoms, specifically chest pain, warrant a comprehensive evaluation.

Heart failure with preserved ejection fraction according to the HFA-PEFF score in COVID-19 patients: clinical correlates and echocardiographic findings.

AIMS: Viral-induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)-like syndromes. COVID-19 can lead to myocardial damage and vascular injury. We hypothesised that COVID-19 patients frequently develop a HFpEF-like syndrome, and designed this study to explore this. METHODS AND RESULTS: Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID-19 patients from April-November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID-19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA-PEFF score. A low (0-1 points), intermediate (2-4 points), and high (5-6 points) HFA-PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID-19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA-PEFF scores were more frequent in COVID-19 patients than controls (25% vs. 4%, P = 0.001). In COVID-19 patients, the HFA-PEFF score significantly correlated with age, estimated glomerular filtration rate, high-sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H2 FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA-PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA-PEFF scores [median 5 (interquartile range 3-6) vs. 1 (0-3), P < 0.001] and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001). CONCLUSION: Hospitalized COVID-19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID-19 patients.