Original research
Nathaniel Moulson,1 Sarah K Gustus,2 Christina Scirica,3 Bradley J Petek ‍ ‍,2,4
Caroyln Vanatta,2 Timothy W Churchill ‍ ‍,2,4 James Sawalla Guseh,2,4
Aaron Baggish,2,4 Meagan M Wasfy ‍ ‍2,4
ABSTRACT
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
1
Cardiology Division, The
symptoms after COVID-­19, compared CPETs in these
University of British Columbia,
athletes and those without COVID-­19 and evaluated
Vancouver, British Columbia,
longitudinal changes in CPET with improvement in
Canada
2
Cardiovascular Performance
symptoms.
Program, Massachusetts
Methods This prospective cohort study evaluated
General Hospital, Boston,
young (18–35 years old) athletes referred for
Massachusetts, USA
3
cardiopulmonary symptoms that were present>28 days
Pediatric Pulmonary Medicine
Division, Massachusetts General from COVID-­19 diagnosis. CPET findings in post-­COVID
Hospital, Boston, Massachusetts, athletes were compared with a matched reference group
USA
of healthy athletes without COVID-­19. Post-­COVID
4
Cardiology Division,
Massachusetts General Hospital, athletes underwent repeat CPET between 3 and 6
months after initial evaluation.
Boston, Massachusetts, USA
Results Twenty-­one consecutive post-­COVID athletes
Correspondence to
with cardiopulmonary symptoms (21.9±3.9 years
Dr Meagan M Wasfy,
old, 43% female) were evaluated 3.0±2.1 months
Cardiovascular Performance
after diagnosis. No athlete had active inflammatory
Program, Massachusetts
heart disease. CPET reproduced presenting symptoms
General Hospital, Boston, MA
in 86%. Compared with reference athletes (n=42),
02114, USA;
m
​ wasfy@​partners.o​ rg
there was similar peak VO2 but a higher prevalence of
abnormal spirometry (42%) and low breathing reserve
Accepted 3 May 2022
(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.
► Additional supplemental
material is published online
only. To view, please visit the
journal online (http://d​ x.​doi.​
org/1​ 0.​1136/b​ jsports-​2021-​
105157).
© Author(s) (or their
employer(s)) 2022. No
commercial re-­use. See rights
and permissions. Published
by BMJ.
To cite: Moulson N,
Gustus SK, Scirica C, et al.
Br J Sports Med Epub ahead
of print: [please include Day
Month Year]. doi:10.1136/
bjsports-2021-105157
WHAT IS ALREADY KNOWN ON THIS TOPIC?
⇒ Persistent or late-­onset cardiopulmonary
symptoms in athletes after COVID-­19 may
occur despite a benign initial illness and may be
associated with elevated risk for inflammatory
heart disease. We sought to describe the results
of cardiac testing in this specific group, with
a focus on the results of cardiopulmonary
exercise testing to identify causes for exertional
symptoms beyond inflammatory heart disease.
WHAT ARE THE FINDINGS?
⇒ In 21 young athletes undergoing diagnostic
evaluation for persistent or late-­onset
cardiopulmonary symptoms following
COVID-­19, no athlete was found to have active
inflammatory heart disease.
⇒ Cardiopulmonary exercise testing (CPET)
successfully reproduced exertional symptoms
in almost all (86%) post-­COVID athletes but
was not associated with significant cardiac
abnormalities, providing reassurance for cardiac
safety. CPET identified abnormal spirometry in
42%, which was associated with low breathing
reserve in some athletes.
⇒ Improvement in cardiopulmonary symptoms
in the 13 athletes followed over time was
accompanied by improvement in CPET
parameters (peak VO2, oxygen pulse, resting
and peak heart rate).
HOW MIGHT IT IMPACT ON CLINICAL
PRACTICE IN THE FUTURE?
⇒ In young athletes with persistent or late-­onset
cardiopulmonary symptoms after COVID-­19,
CPET was clinically useful. CPET identified either
normal testing allowing for clinical reassurance
or abnormal spirometry associated with low
breathing reserve in some athletes, which
represents a potential therapeutic target worthy
of further investigation.
INTRODUCTION
COVID-­
19 caused by the SARS-­
CoV-­
2 virus is
a multisystem illness that can involve the pulmonary and cardiovascular systems.1 Young athletes
are relatively protected from severe acute sequelae
of COVID-­19.2 3 However, prolonged effects of
COVID-­19, now defined as postacute sequelae of
SARS-­CoV-­2 (PASC), may occur even in those with
mild acute illness.4 5 Current data suggest that the
prevalence of PASC may be lower in young competitive athletes (1.2%–14%)6 7 than in the general
population (26%–39%).5 8 However, due to the
large number of COVID-­19 cases, the evaluation
of ongoing symptoms, particularly those suggestive
of cardiopulmonary origin, remains an important
issue in post-­COVID athletes’ clinical care.9
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi:10.1136/bjsports-2021-105157
1
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Diagnostic evaluation and cardiopulmonary exercise
test findings in young athletes with persistent
symptoms following COVID-­19
Original research
METHODS
Study setting
The Cardiovascular Performance Program (CPP) at the Massachusetts General Hospital (Boston, Massachusetts, USA) provides
clinical cardiovascular care to athletes. From the programme’s
exercise laboratory opening (1 October 2011) through present,
patient data including CPET results were prospectively collected
in a research database.24 Athletes presenting to the CPP for clinical evaluation of cardiopulmonary symptoms after COVID-­19
were approached regarding enrolment in a longitudinal CPET
study. Data presented for post-­COVID athletes are from the
baseline clinical evaluation, which occurred between 1 July 2020
and 1 May 2021, and from follow-­up research assessment occurring 3–6 months later. Post-­COVID athletes were matched (1:2),
as detailed in the online supplemental methods, with a reference
athlete group without COVID-­19 from the research database
(online supplemental figure 1).
Study population: post-COVID athletes
Individuals were eligible for study inclusion in the post-­COVID
group if they were young (aged 18–35) athletes referred for
persistent or late-­
onset cardiopulmonary symptoms after
COVID-­
19 (defined in the online supplemental methods).
Persistent symptoms were defined as those present during acute
illness (defined as the first 14 days) and continuing >28 days
from diagnosis. Late-­onset symptoms were defined as those that
newly appeared between 14 and 28 days (eg, most commonly on
return to exercise) and were still present >28 days from diagnosis. Cardiopulmonary symptoms were defined as exertional
2
intolerance, chest pain, dyspnoea, palpitations, lightheadedness,
syncope and cough.
Clinical and research evaluation: post-COVID athletes
All eligible athletes underwent clinical evaluation including
history and physical examination. Participants completed
a research survey detailing symptoms present during the
acute phase (<14 days) that continued or newly appeared
at 14–28 days, and that were still present after 28 days from
COVID-­
19 diagnosis. All eligible athletes completed a clinically indicated CPET. Other initial clinical evaluation included
12-­lead ECG, high sensitivity troponin (hs-­troponin) level and
cardiac imaging (transthoracic echocardiography (TTE) and/
or cardiac MRI (CMR)) per contemporaneous guidelines.25 26
ECGs and cardiac imaging were assessed for normality using
athlete-­specific guidelines.27 28 To assess the longitudinal trajectory of symptoms and CPET findings, all athletes were invited
for follow-­up research assessment occurring 3–6 months after
initial clinical evaluation, which included survey reassessment of
symptoms and repeat CPET.
Cardiopulmonary exercise testing
All CPETs were performed in a single laboratory. Patients underwent an intensity-­
graded, maximal effort exercise test with
continuous gas exchange (Ultima CardiO2; Medgraphics Diagnostics) on the treadmill (Woodway Pro 27, Woodway) or the
upright cycle ergometer (Sport Excalibur Bicycle Ergometer,
Lode). The exercise protocols and definitions of CPET parameters are detailed in the online supplemental methods.24
Statistical analysis
Continuous variables were described using means and SD or
medians and IQR and compared between groups (reference
athletes, post-­
COVID athletes at first vs second assessment)
using the Student’s t-­test, Mann-­Whitney U test or paired t-­test
as appropriate. Categorical variables are presented as n (%) and
compared by χ2, McNemar’s or Fisher’s exact test as appropriate. Analyses and graphical displays were generated using
GraphPad (Prism V.7.0d).
RESULTS
Post-COVID athlete characteristics
The cohort consisted of a total of 21 consecutive young athletes
(21.9±3.9 years old, 9 female (43%)) who were evaluated
for persistent or late-­
onset cardiopulmonary symptoms after
COVID-­19. Athletes presented 3.0±2.1 months after diagnosis
(range 1.2–8.5 months). The majority (n=16, 76%) presented
between January and April 2021, and as such none had been
vaccinated for COVID-­19 at the time of infection.29 Baseline
characteristics are presented in table 1; no athlete had known
cardiac disease.
All athletes were symptomatic during their acute illness, with
1 (5%) having mild, 8 (38%) having moderate illness without
cardiopulmonary symptoms and 12 (57%) having at least one
acute cardiopulmonary symptom. Initial symptoms and those
present >28 days after diagnosis are shown in figure 1A. A
total of 14 (67%) athletes developed at least one new late-­onset
cardiopulmonary symptom that was not present during acute
infection but arose between 14 and 28 days after infection, with
48% developing ≥2 late-­onset cardiopulmonary symptoms. All
athletes reported at least one persistent or late-­onset exertional
cardiopulmonary symptom (figure 1B).
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi:10.1136/bjsports-2021-105157
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Return-­to-­play screening in young athletes after COVID-­19
has focused on the detection of inflammatory heart disease, such
as myocarditis or pericarditis.10–12 However, a diagnostic evaluation solely focused on inflammatory heart disease may miss
sequelae of COVID-­19 impacting other systems that cooperate
to produce an exercise effort. This is particularly relevant in
an athlete presenting with symptoms suggestive of cardiopulmonary origin that newly appear (referred to as ‘late onset’) or
persist after the acute phase of COVID-­19 because the likelihood of active inflammatory heart disease causing these symptoms diminishes over time.12 13 In the absence of inflammatory
heart disease, alternate causes of persistent or late-­onset cardiopulmonary symptoms in young athletes after COVID-­19 have
not been well defined.
Cardiopulmonary exercise testing (CPET) allows for integrated assessment of exercise performance and is a tool that can
both help calibrate concern for cardiac pathology and assess for
abnormalities in other relevant organ systems in patients with
cardiopulmonary symptoms. While others have begun to explore
the aetiology of cardiopulmonary symptoms after COVID-­19
using CPET,14–23 none have done so in athletes specifically
onset symptoms. We therefore
selected for persistent or late-­
undertook the current study with three a priori objectives.
First, we sought to assess the diagnostic yield of cardiac evaluation, including CPET, in this specific population of athletes
with cardiopulmonary symptoms after COVID-­19. Second, to
better identify the specific impact of COVID-­19, we compared
CPET findings in these post-­COVID athletes to those in a reference group of healthy athletes who had not had COVID-­19.
Finally, we evaluated these athletes with persistent or late-­onset
cardiopulmonary symptoms after COVID-­19 longitudinally to
describe improvement in symptoms and change in CPET parameters over time.
Original research
Post-COVID athlete CPET results
Demographic information
Post-­COVID
athletes
(n=21)
Reference athletes
(n=42)
Age
21.9±3.9
21.9±3.8
Female sex
9 (43)
18 (43)
White (non-­Hispanic/Latino)
17 (81)
37 (88)
Black
2 (10)
1 (2)
Asian
1 (5)
1 (2)
White (Hispanic/Latino)
1 (5)
3 (7)
Height (cm)
175.2±13.0
174.3±11.6
Weight (kg)
72.8±17.0
73.9±16.7
BMI (kg/m2)
23.4±2.6
24.1±3.2
Endurance
5 (24)
10 (24)
Team sport
11 (52)
22 (52)
Mixed/other
5 (24)
10 (24)
High school
1 (5)
2 (5)
Collegiate
14 (67)
28 (67)
Postcollegiate
4 (19)
8 (19)
Recreational athlete
2 (10)
4 (10)
None
9 (43)
20 (48)
Current asthma
3 (14)
6 (14)
Childhood asthma
2 (10)
5 (12)
Anxiety/depression
3 (14)
1 (2)
Attention Deficit Hyperactivity
Disorder
3 (14)
8 (20)
Other
6 (29)
9 (21)
None
9 (43)
21 (50)
Contraception (pill/device)
6 (29)
5 (12)
Albuterol
3 (14)
5 (12)
Stimulant
2 (10)
7 (17)
Other
7 (32)
10 (24)
Race/ethnicity
Sport type
Level of competition
Competitive athlete
Medical history
Baseline medications
BMI, body mass index.
Post-COVID athlete testing results
Symptoms present at the time of clinical evaluation and
testing results are shown in online supplemental table 1.
Testing included hs-­
troponin, ECG, cardiac imaging and
CPET in all athletes. No athlete had an abnormal TTE or
ECG, apart from resting sinus tachycardia in two athletes
(10%). TTE was performed in 19 athletes, of whom 11 also
underwent CMR due to elevated suspicion for inflammatory
heart disease based on the presence/extent of cardiopulmonary symptoms (n=10) or mildly elevated hs-­troponin (n=1).
Two athletes had a CMR not preceded by TTE. No athlete
had imaging evidence of active inflammatory heart disease.30
Five CMRs (38%) demonstrated isolated late gadolinium
enhancement (LGE). LGE was confined to the right ventricular (RV) insertion point or a single segment in four athletes.
One athlete had patchy subepicardial and pericardial LGE
without elevated inflammatory markers or hs-­troponin, pericardial effusion or evidence of pericarditis on examination
or ECG.30 No athlete had evidence of myocardial oedema,
which is required in combination myocardial injury (eg, LGE)
to establish active myocarditis.
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi:10.1136/bjsports-2021-105157
CPET results are summarised in table 2. Eighteen athletes
(86%) reported the development of their presenting exertional
symptom(s) during CPET (online supplemental table 1). Three
athletes (14%) had abnormal peak oxygen consumption (pVO2,
<80% predicted) and three (14%) athletes had low-­
normal
pVO2 (≥80% but <90% predicted). One athlete demonstrated
a symptomatic fall in blood pressure immediately (<1 min) after
exercise, with reproduction of presenting complaint of lightheadedness. A second athlete had blunted augmentation of systolic
blood pressure with reproduction of presenting complaint of
dyspnoea. All athletes completed screening spirometry prior to
CPET; two athletes’ spirometry represented insufficient effort
or quality and was excluded from analysis. Of the remaining
athletes, spirometry was abnormal in 8/19 (42%), with 6/19
having both abnormal forced expiratory volume in 1 s (FEV1)
and FEV1/forced vital capacity (FVC), and two athletes having
either abnormal FEV1/FVC (n=1) or FEV1 (n=1).31 Most (88%)
with abnormal spirometry did not have current or childhood
asthma. The exercise ECG did not reveal ischaemic changes or
clinically significant arrhythmias in any athlete.
Comparison with reference athlete CPETs
Reference athletes’ demographics were similar to post-­COVID
athletes (table 1). Post-­
COVID and reference athletes had
similar pVO2 and VO2 at the ventilatory threshold (table 2). As
compared with reference athletes, post-­COVID athletes’ FEV1
as a per cent of predicted (86±16 vs 98±12, p<0.01) and
FEV1/FVC (0.74±0.11 vs 0.86±0.06, p<0.001) were lower.
Post-­
COVID athletes had a higher prevalence of abnormally
low peak exercise breathing reserve (42% vs 12%, p<0.05)
than reference athletes. In post-­COVID athletes, low breathing
reserve occurred most often in those with both abnormal resting
spirometry and normal fitness (pVO2 80%–120% predicted; 4/8
or 50%) in whom it may represent a true pulmonary limit, rather
than in those with normal resting spirometry and supranormal
fitness (pVO2 ≥120% predicted; 3/8 or 38%) in whom it may
be physiologic.
Longitudinal post-COVID athlete evaluation
Thirteen athletes (62%) underwent a follow-­up research evaluation at 4.8±1.9 months after initial assessment. There were
no significant differences in the demographic and CPET parameters in tables 1 and 2 between those athletes who did and did
not complete follow-­up (all p>0.05). Nine athletes (69%) had
resolution of (n=6, 46%) or reduction in (n=3, 23%) cardiopulmonary symptoms at follow-­up (figure 2A). Compared with the
first post-­COVID CPETs, follow-­up CPETs demonstrated lower
resting heart rate (HR) (81±15 vs 75±10, p<0.05) and peak
exercise HR (188±9 vs 183±9, p<0.05) (figure 2C), with no
use of medications known to impact HR and similar effort as
assessed by the respiratory exchange ratio. pVO2 increased from
3.39 L/min±0.69 (117±36% predicted) to 3.62 L/min±0.81
(123±38% predicted, p<0.05, figure 2B). The combination of
lower peak HR and higher pVO2 resulted in higher peak oxygen
pulse in 11/13 (85%) at follow-­up (figure 2D). Similarly, the
chronotropic index, which defines the change in exercise HR
relative to VO2 accounting for predicted values, was lower on
the follow-­up versus the first CPET (0.77±0.20 vs 0.85±0.23,
p<0.05, online supplemental table 2). There was numerical
improvement in FEV1 (3.8±1.0 to 4.1±0.9 L, p>0.05) and
FEV1/FVC (0.75±0.12 to 0.79±0.09, p>0.05) that was not
statistically significant, and normalisation of abnormal FEV1
3
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Table 1
Original research
in two of three athletes in whom this was abnormal at baseline (online supplemental table 2). On follow-­
up evaluation,
the exercise ECG did not reveal ischaemic changes or clinically
significant arrhythmias in any athlete.
DISCUSSION
This study was conducted to assess the diagnostic yield of cardiac
evaluation including CPET and describe follow-­
up of young
athletes with persistent or late-­onset cardiopulmonary symptoms
following COVID-­19. Key findings are summarised as follows.
First, while no athlete in this study was asymptomatic during
acute illness, the majority of athletes developed at least one
new late-­onset cardiopulmonary symptom that was not present
during acute infection. This highlights the need for ongoing clinical assessment as symptoms may only become evident under
the physiological stress of returning to exercise. Second, CPET
was clinically valuable in this population as it successfully reproduced athletes’ presenting symptoms in the absence of significant
cardiac abnormalities, allowing for reassurance. CPET also identified a high prevalence of abnormal spirometry and associated
low breathing reserve, which may provide an alternate cause for
symptoms and a potential target for treatment. Third, longitudinal evaluation identified small but significant improvements
in several CPET parameters that accompanied symptomatic
recovery, which may relate to resumption of training or resolution of direct COVID-­19 impact. Finally, while the primary
focus of return-­to-­play evaluation has been on the exclusion of
inflammatory heart disease, diagnostic evaluation (online supplemental figure 2) revealed no active inflammatory heart disease
despite a high cardiopulmonary symptom burden. These results
emphasise the importance of consideration for both inflammatory heart disease and other relevant and treatable cardiopulmonary diagnoses in young athletes presenting with persistent or
late-­onset symptoms after COVID-­19.
Clinical utility of CPET in symptomatic post-COVID athletes
Our results demonstrate that CPET is a valuable clinical tool in
the population of young athletes with persistent post-­COVID
4
symptoms. We previously demonstrated that appropriately
customised CPET was effective at reproducing presenting symptoms in athletes without COVID-­19, allowing for either the identification of relevant cardiopulmonary diagnoses or reassurance
in the presence of normal testing.32 The current study reaffirms
these findings, with almost all athletes reporting their presenting
symptoms during the test and most having either normal tests
or abnormal resting spirometry. The CPET findings observed, in
particular the abnormal resting spirometry coupled in some with
low breathing reserve, while not posing risk to return to sport,
represent potential opportunities to trial intervention to improve
exertional symptoms. Overall, symptom provocation coupled
with CPET results in this post-­COVID population allowed for
provision of reassurance when combined with a comprehensive
evaluation, identified potentially treatable abnormalities and
facilitated gradual return to play with close clinical follow-­up.
Insights into post-COVID symptoms from follow-up
evaluation
Our longitudinal data reveal a reassuring reduction in cardiopulmonary symptoms over time in post-­COVID athletes. Despite no
differences in pVO2 at baseline between post-­COVID and reference athletes, there was improvement in pVO2 with concomitant improvement in symptoms in post-­COVID athletes. These
data suggest that deficits in pVO2 and detraining may have been
underappreciated as a cause for symptoms in these athletes’
initial evaluation, particularly with the use of prediction equations derived in the general population.24 While data on physical activity at the two time points were not systematically
collected, the improvement in pVO2 and reduction in resting HR
over these athletes’ recovery period may represent a retraining
effect from return to sport, and underscore the importance of
resumption of exercise once an adequately reassuring cardiac
evaluation is complete in order to support continued recovery.
Conversely, lower peak HR on follow-­up CPET is not explained
by retraining, and may indicate COVID-­19 impact on the autonomic response to exercise as has been suggested by others’
work in the general population33–36 and one prior longitudinal
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi:10.1136/bjsports-2021-105157
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Figure 1 Symptom prevalence. (A) Prevalence of self-­reported symptoms during acute COVID-­19 (<14 days from diagnosis) and that were persistent
(>28 days from diagnosis) or late onset (newly appeared 14–28 days and were still present>28 days from diagnosis) in athletes. (B) Prevalence of self-­
reported persistent or late-­onset cardiopulmonary symptoms that occurred during exertion.
Original research
Cardiopulmonary exercise test data
Post-­COVID athletes
(n=21)
Reference athletes
(n=42)
Testing modality
Cycle ergometer
9 (43)
18 (43)
Treadmill
12 (57)
24 (57)
Vital signs
Baseline HR (beats per minute)
86±16
81±14
Peak HR (beats per minute)
189±9
189±9
Percent predicted
95±4
95±4
Heart rate recovery (beats per minute)
44±12
46±11
Baseline SBP (mm Hg)
122±11
119±11
Peak SBP (mm Hg)
168±21
172±24
Baseline DBP (mm Hg)
75±6
77±8
Peak DBP (mm Hg)
77±5
70±12†
Baseline O2 saturation (%)
98±1
98±1
O2 saturation (%) at peak exercise
96±2
96±2
Spirometry*
Pre-­exercise FEV1 (L)
3.7±1.1
4.1±1.0
Percent predicted (%)
86±16
98±12†
Abnormal (below 5th percentile)
7 (37)
3 (7)†
Pre-­exercise FVC (L)
4.9±1.1
4.8±1.1
Percent predicted (%)
98±10
98±13
Pre-­exercise FEV1/FVC
0.74±0.11
0.86±0.06†
Abnormal (below 5th percentile)
7 (37)
1 (2)†
Respiratory exchange ratio
1.17±0.09
1.17±0.08
Peak VO2 (L/min)
3.2±0.7
3.4±0.9
Peak VO2 (mL/kg/min)
44.6±9.1
46.4±9.6
Percent predicted (%)
110±30
114±23
1 (2)
Gas exchange
Abnormal (<80% predicted)
3 (14)
VO2 at VT (mL/kg/min)
35.7±11.3
36.0±10.3
Chronotropic index
0.89±0.24
0.83±0.17
Oxygen pulse (mL/beat)
16.8±4.2
18.1±4.9
Total VE/ VCO2 slope
28.1±3.4
28.2±4.0
VE/ VCO2 slope through VT
24.6±3.3
24.3±3.2
Peak VE (L/min)
112±32
120.±37
Breathing reserve (%)*
18±20
25±19
Low breathing reserve (<10%)
8 (42)
5 (12)†
*Two post-­COVID athletes’ spirometry measurements (1 male, 1 female) were excluded due
to low quality.
†P<0.05 for post-­COVID athletes versus reference athletes.
DBP, diastolic blood pressure; FEV1, forced expiratory volume in 1 s; FVC, forced vital
capacity; HR, heart rate; SBP, systolic blood pressure; VCO2, carbon dioxide production; VE,
ventilation; VO2, oxygen consumption; VT, ventilatory threshold.
study in variably symptomatic athletes.19 Our results identify
important directions for future in-­depth work aimed at better
delineating the relationships among persistent cardiopulmonary
symptoms after COVID-­19, detraining and retraining, and these
exercise testing parameters.
Comparison to prior published work: CPET and spirometry
Whereas other studies have evaluated post-­COVID CPET or
spirometry findings either in non-­athletes with persistent symptoms or in athletes who were not selected for persistent symptoms,14–23 to our knowledge, this study is the first to focus on
CPET findings in young post-­COVID athletes with persistent
or late-­onset cardiopulmonary symptoms. Despite the presence
of prominent symptoms, most athletes in our cohort did not
demonstrate significant abnormalities of ventilatory efficiency
or pVO2 on their first CPET, which is consistent with others’
results in variably symptomatic athletes.16 17 20 22 Conversely, we
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi:10.1136/bjsports-2021-105157
observed a high proportion of post-­COVID athletes with mild
abnormalities in screening spirometry. Our study is limited in
that baseline pre-­
COVID spirometry was not available and,
with a focus on ruling out cardiac disease, full and appropriately customised pulmonary evaluation was not systematically
performed. Therefore, we cannot delineate if the higher prevalence of abnormal spirometry in post-­
COVID as compared
with reference athletes was due to COVID-­19 or reflects baseline differences between the groups despite careful matching.
Others have reported mild decreases in FEV1 in athlete cohorts
that were not selected for persistent symptoms as compared with
pre-­COVID values15 or controls,16 which support the possibility
that the observed spirometry abnormalities in our study were
due to COVID-­19. Given incomplete longitudinal improvement,
our study may have been enriched for athletes with mild baseline spirometry abnormalities, and future work should identify if
such athletes are at higher risk of developing persistent cardiopulmonary symptoms after COVID-­19 or if this represents a
limitation of our small cohort size. Overall, our results highlight
an important area of future work given the potential for focused
pulmonary intervention that may facilitate symptom resolution
and return to sport.
Diagnostic approach in symptomatic post-COVID athletes
The diagnostic evaluation of young athletes presenting with
persistent or late-­onset symptoms following COVID-­19 infection remains a clinical challenge. Our results highlight that
athletes may develop new late-­
onset cardiopulmonary symptoms, typically when returning to exercise, despite a benign
acute course. While it is appropriate that the presence of these
symptoms prompts clinical concern,37 active inflammatory
heart disease after COVID-­19 is rare11 12 and was not present
in athletes in this cohort despite a high burden of cardiopulmonary symptoms. Our cohort demonstrated a sizeable prevalence
of isolated LGE, which is in line with data from other athlete
cohorts without COVID-­19 suggesting that LGE, particularly
when located at the RV insertion point, is common with unclear
clinical significance.38–40 Limited data suggest that active inflammatory heart disease after COVID-­19 resolves within 3 months
on follow-­up imaging,12 which further diminishes the likelihood
that symptoms may be ascribed to active inflammatory heart
disease the later the athlete presents for evaluation after infection.13 Our diagnostic approach (online supplemental figure 2)
integrates symptoms, initial testing, other explanatory diagnoses
and time since infection to calibrate suspicion for inflammatory
heart disease in athletes presenting with persistent or late-­onset
cardiopulmonary symptoms, and outlines initial steps, such as
CPET, in this patient population that may identify alternate
causative diagnoses.
Limitations
There are several limitations to this study in addition to those
outlined above. First, athletes were referred to a sports cardiology practice for assessment of cardiopulmonary symptoms
and represent a highly select subgroup of post-­COVID athletes.
Despite this selection, no athlete had active inflammatory heart
disease. Importantly, current data7 support and return-­to-­play
protocols13 26 41 specify further cardiology evaluation for exactly
this type of athlete. Therefore, our work, which assesses the
totality of the cardiac evaluation including CPET in this group,
provides data in the small proportion of athletes who still
require further clinical evaluation prior to return to play after
COVID-­19. Second, a complete pulmonary evaluation including
5
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Table 2
Original research
full pulmonary function testing and pulmonary imaging was not
systematically performed as part of this initial evaluation, whose
primary goal was ruling out inflammatory heart disease. We also
did not systematically collect downstream data on athletes’ non-­
cardiac medical management. While this limits our ability to
define the pulmonary impact of COVID-­19, our results provide
important preliminary results in an area meriting further study.
Third, the absence of baseline diagnostic testing before COVID-­
19, specifically prior CPET and spirometry, and the incomplete
longitudinal follow-­up in our cohort limit our ability to conclude
whether demonstrated abnormalities were pre-­existing, resulted
from COVID-­19 or were due to associated detraining. However,
the use of a well-­matched reference group of athletes and longiCOVID
tudinal data on a representative subgroup of post-­
athletes help highlight the deficits that are most likely to relate to
persistent or late-­onset cardiopulmonary symptoms in athletes
after COVID-­19.
CONCLUSION
In a cohort of young athletes presenting with a high burden
of persistent or late-­
onset cardiopulmonary symptoms after
COVID-­19, no athlete was found to have active inflammatory
heart disease. CPET demonstrated clinical utility by provoking
presenting symptoms in the setting of largely normal testing
results, thus allowing for patient reassurance, and by identifying
abnormalities in resting spirometry and breathing reserve that
may serve as therapeutic targets. Improvement in cardiopulmonary symptoms over time was accompanied by small but significant improvement in CPET parameters. Further work is needed
to better characterise the pulmonary contributions to persistent
or late-­
onset cardiopulmonary symptoms and to define the
relative contributions of retraining versus resolution of a direct
impact of COVID-­19 on post-­COVID athletes.
Funding MMW received funding for this study from the Massachusetts General
Hospital COVID Junior Investigator Support Grant. NM is supported by the University
of British Columbia Clinician Investigator Program.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in
the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study involves human participants and was approved by
the Massachusetts General Brigham (MGB) Institutional Review Board (study IDs:
2018P00753, 2021P00064), as detailed in the online supplemental methods.
Participants gave informed consent to participate in the study before taking part.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
Supplemental material This content has been supplied by the author(s).
It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not
have been peer-­reviewed. Any opinions or recommendations discussed are
solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all
liability and responsibility arising from any reliance placed on the content.
Where the content includes any translated material, BMJ does not warrant the
accuracy and reliability of the translations (including but not limited to local
regulations, clinical guidelines, terminology, drug names and drug dosages), and
is not responsible for any error and/or omissions arising from translation and
adaptation or otherwise.
This article is made freely available for personal use in accordance with BMJ’s
website terms and conditions for the duration of the covid-­19 pandemic or until
otherwise determined by BMJ. You may download and print the article for any lawful,
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ORCID iDs
Bradley J Petek http://orcid.org/0000-0002-6603-2262
Timothy W Churchill http://orcid.org/0000-0002-0215-3049
Meagan M Wasfy http://orcid.org/0000-0003-0398-0481
REFERENCES
Contributors NM helped design the study, monitored the data collection, cleaned
and analysed the data, and drafted and revised the paper. SKG designed the survey
tool, monitored the data collection, cleaned and analysed the data and revised the
paper. CS analysed the data and revised the paper. BJP generated the figures and
revised the paper. CV monitored the data collection, cleaned the data and revised
the paper. TWC revised the draft paper. JSG revised the draft figures and the draft
paper. AB helped design the study and revised the draft paper. MMW designed the
study, monitored the data collection, cleaned and analysed the data, and drafted
and revised the figures and paper. MMV is the guarantor of the study.
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Twitter Nathaniel Moulson @NateMoulson_MD, Timothy W Churchill
@TimChurchillMD and Meagan M Wasfy @meaganwasfy
Br J Sports Med: first published as 10.1136/bjsports-2021-105157 on 18 May 2022. Downloaded from http://bjsm.bmj.com/ on May 21, 2022 by guest. Protected by copyright.
Figure 2 Longitudinal follow-­up symptoms and cardiopulmonary exercise testing (CPET) data. (A) Prevalence of self-­reported symptoms at the time
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Supplemental material
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Methods Supplement
Institutional Review Board Approval & Consent
Two separate protocols (2018P00753, 2021P00064) approved by the Mass General Brigham (MGB)
Institutional Review Board (IRB) cover all aspects of this study. One protocol covers the prospective clinical
CPET database from which the matched reference athlete cohort was obtained. The protocol outlines for
accessing patient’s medical records to ascertain health conditions and view other cardiac testing. The need for
informed consent from patients whose clinical CPETs are included in the database was waived by the IRB, as
there is no contact or interaction with patients beyond that which is required for their clinical care. A second
protocol covers all aspects of the prospective longitudinal study of post-COVID athletes, including the
symptoms surveys and second research CPETs presented here. All post-COVID athletes participating in the
longitudinal study underwent informed consent as outlined by the IRB-approved protocol.
Athlete & COVID-19 Illness Definitions
Competitive athletes were defined as those completing dedicated exercise training for competitive
individual or team-based goals; recreational athletes were defined as those completing dedicated exercise
training without competitive goals. Predominate sport type was categorized into team (e.g. football, soccer,
volleyball, basketball, or lacrosse), endurance (e.g. long-distance running, cycling, triathlon, rowing and/or
swimming), or mixed / other (participating in multiple sports, or participating in a sport not meeting endurance
or team definitions).
Confirmed SARS-CoV-2 infection was defined as a positive polymerase chain reaction (PCR) or
antigen test. Acute presentation with COVID-19 was defined as mild if only fatigue, gastrointestinal symptoms
(nausea, vomiting, diarrhea), headache, anosmia, ageusia, rhinorrhea, sore throat, or nasopharyngeal congestion
were present; moderate if chills, fever or myalgias were present; or cardiopulmonary if exertional intolerance,
chest pain, dyspnea, palpitations, lightheadedness, syncope, or cough were present.1 If an athlete had symptoms
in multiple categories, they were assigned the most severe category with cardiopulmonary symptoms considered
of greater severity than moderate.
Study Population: Matched Healthy Athletes
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To generate a reference group to compare CPET findings in the post-COVID athletes, we matched each
post-COVID-19 athlete (n=21) with two healthy athletes from our research database. From all athlete tests in
the database (n=1837), a healthy cohort of 566 athletes was available for potential matching. Unless clinically
contraindicated, patients referred to the program undergo a CPET in conjunction with their clinical intake visit.
All healthy athletes had been referred for clinically indicated CPETs either prior to the pandemic (n=39) or
during the pandemic but without a clinical history and/or testing consistent with COVID-19 (n=3). As
previously published in detail, rigorous exclusion criteria derived from the CPET itself, the medical history
including diagnoses made as the result of the CPET, and transthoracic echocardiography were used to generate
the cohort of athletes free of cardiac disease available for matching (n=566/1837, Supplemental Figure).2 The
one difference from the published workflow is that we allowed patients with abnormal spirometry into the
cohort for matching.
A group of potential reference athletes was generated for each post-COVID-19 athlete that was exactly
matched for sex, test type (treadmill vs. cycle ergometer), sport type as defined above, and diagnosis of current
asthma. Within these groups, reference athletes were sought for each post-COVID-19 athlete that matched age
± 1 year and weight ± 5 kilograms. If there were more than two matched reference athletes, those two reference
athletes with the closest weight were chosen as the final matches. Successfully matched reference athletes were
removed from the pool of potential matches. If two matches were not available for a given post-COVID-19
athlete, additional reference athletes were sought that matched age ± 2 years and weight ± 15 kilograms. Again,
if there were more than two total matched reference athletes, those two reference athletes with the closest
weight were chosen as the final matches. Using this algorithm, two healthy reference athletes were matched for
each post-COVID athlete.
The most common reasons for CPETs in reference athletes (n=42) were palpitations (33%), chest pain
(21%), syncope (14%), and presyncope/lightheadedness (14%). As per exclusion criteria (Supplemental
Figure), the presenting symptom(s) were found to be due to a clinically benign and/or non-cardiac entity (e.g.,
non-cardiac chest pain, neurocardiogenic syncope, ectopic beats).
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi: 10.1136/bjsports-2021-105157
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Cardiopulmonary Exercise Testing Methods
All participants underwent an intensity graded, maximal effort-limited exercise test with continuous gas
exchange on either the treadmill (Woodway Pro 27, Woodway USA, Waukesha, Wisconsin) or the upright
cycle ergometer (Sport Excalibur Bicycle Ergometer, Lode, Holland) as previously described.2 Briefly, the
exercise modality was chosen by the participant and exercise physiologist with the goal of matching testing to a
participant’s primary form of exercise. The cycle ergometry test protocol consisted of 3 minutes of free-wheel
cycling followed by continual increase in resistance (varying from 10 to 40 watts per minute) until test
completion. Treadmill tests began with a 5-minute warm-up at 3.0 to 7.5 miles per hour and 1% grade followed
by a progressive increase in incline (0.5% grade increase every 15 seconds) at a fixed speed until exhaustion.
The intensity of the cycle ergometry ramp and the speed of treadmill testing were determined by the overseeing
exercise physiologist in conjunction with the participant with a goal of reaching a 10 minute total ramp time.
The exercise modality was chosen by the participant and exercise physiologist with the goal of matching testing
to a participant’s primary form of exercise.
Gas exchange was measured on a breath-by-breath basis using a Hans Rudolph V2 Mask (Hans
Rudolph, Inc, Shawnee, Kansas), a commercially available metabolic cart and gas exchange analyzer (Ultima
CardiaO2; Medgraphics Diagnostics, St. Paul, Minnesota) and analyzed using Breeze Suite software
(Medgraphics Diagnostics, Version 8.2, 2015). Continuous 12-lead ECG monitoring (Mortara Instrument X12+
wireless ECG transmitter, Milwaukee, Wisconsin) was performed and blood pressures were measured using a
manual sphygmomanometer before exercise, at three- minute intervals during exercise, at peak exercise, and
during recovery. Participants were instructed to report the development of any cardiopulmonary symptoms
during testing, and at test termination were asked to rate the maximal severity of these symptoms during testing
on a 1-10 Likert scale, with 1 being minimal and 10 being worst possible severity.
Test termination was determined by volitional exhaustion and maximal effort was confirmed by a peak
respiratory exchange ratio >1.05 and a maximal heart rate of > 85% age/gender predicted pea values.
oxygen consumption p
2)
ea
was defined as the highest oxygen uptake over a period of 30 seconds over the last
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minute of effort-limited exercise and was assessed for normality using the Jones equations derived in the
general population.3 4 An a normally low p
was defined as ≥
ut 9
2
was defined as
predicted and a low-normal p
2
predicted. The peak respiratory exchange ratio was defined as exhaled carbon
dioxide divided by oxygen consumption using the same 30 second average. The ventilatory threshold was
determined using gas exchange data, specifically the V-slope method with complementary assessment of
ventilatory equivalents and end-tidal gases as previously described.5 Resting sinus tachycardia was defined as
resting heart rate (HR) of > 100 beats per minute. An abnormal blood pressure (BP) response was defined as
blunted BP augmentation (systolic BP fall or rise < 20 mmHg)6-8 or a rapid fall in the first minute of postexercise BP, with accompanying reproduction of presenting symptoms. Normal heart rate recovery was defined
as a reduction of >24bpm at 2 minutes into recovery. Abnormal breathing reserve was defined as
exercise and calculated as
aximal
1)).
at pea
The peak oxygen pulse was calculated as pVO2 / peak
HR. The chronotropic index was calculated as: ((Peak HR-Baseline HR)/(Predicted Peak HR-Baseline
HR))/((PVO2-Baseline VO2)/(Predicted PVO2-Baseline VO2)).9
Spirometry was performed both immediately prior to exercise according to American Thoracic Society
(ATS)/European Respiratory Society (ERS) acceptability and repeatability criteria10, using a standard
mouthpiece with a preVent flow sensor (Medgraphics Diagnostics, St. Paul, Minnesota) attached to the
metabolic cart. Normality of the best forced expiratory volume in one second (FEV1) and forced vital capacity
(FVC) pre-exercise was assessed using predicted equations from the Global Lung Function Initiative (GLI).11
FEV1, FVC, and FEV1/FVC were considered abnormal if <5th percentile (-1.645 Z-score). If the FEV1/FVC was
abnormal, the degree of obstruction was graded as mild (FEV1≥ 7
predicted) moderate FEV1 60-69%
predicted), moderately severe (FEV1 50-59% predicted), severe (FEV1 35-49% predicted), and very severe
(FEV1 <35% predicted).
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Supplemental material
Br J Sports Med
Supplemental Table 1. Post-COVID Athletes: Clinical Presentation & Testing
Athlete
Age
&
Sex
Sport
Type
Time to
Evaluation
from
COVID-19
Diagnosis
2.8 months
Persistent
Cardiopulmonary
Symptoms
Laboratory
Results
ECG
TTE
CMR
CPET:
Symptoms During
Test
& Key Findings
Other Testing
1
19M
Team
Sport
Chest pain
HS-Trop.: mildly elevated
Repeat 1wk. later: normal
Normal
Normal
Normal
+Chest Pain (4/10)
 Normal test
Patch monitor:
normal
2
25M
Mixed
2.2 months
Dyspnea
Lightheadedness
Exercise intolerance
Normal
Normal
Normal
--
+Dyspnea (7/10)
+Lightheadedness
(6/10)
 Abrupt fall in postexercise BP
Patch monitor:
normal
3
20F
Team
Sport
1.4 months
Chest pain
Dyspnea
Normal
Sinus
Tach.
Normal
Normal
+Chest Pain (5/10)
+Dyspnea (9/10)
 Resting sinus tach.
 Moderately severe
obstructive defect
 Low breathing
reserve
4
19M*
Team
Sport
2.7 months
Chest pain
Palpitations
Lightheadedness
Normal
Normal
Normal
Normal
+Chest Pain (7/10)
+Lightheadedness
(2/10)
 Peak VO2 89%
predicted
Patch Monitor:
normal
5
21F
Team
Sport
4.0 months
Chest pain
Palpitations
Lightheadedness
Normal
Normal
Normal
--
 Moderate
obstructive defect
 Low breathing
reserve
Patch Monitor:
normal
6
18F
Endurance
1.3 months
Chest Pain
Dyspnea
Elevated D-dimer
Normal
Normal
Normal
+Chest Pain
+Dyspnea
 Resting sinus
tach.**
CT Pulmonary
Angiogram:
normal
7
29F
Endurance
4.9 months
Dyspnea
Palpitations
Lightheadedness
Exercise intolerance
Normal
Normal
Normal
LGE: Subtle,
mid-wall
LGE in mid
lateral LV
segment
+Dyspnea (8/10)
+Lightheadedness
(5/10)
 Resting sinus tach.
 Low breathing
reserve
Patch monitor:
normal
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8
31F
Endurance
8.5 months
Dyspnea
Palpitations
Exercise intolerance
Normal
Normal
Normal
--
+Dyspnea (5/10)
 Normal test
Patch Monitor:
normal
9
25M
Mixed
1.6 months
Chest pain
Dyspnea
Palpitations
Cough
Exercise intolerance
Normal
Normal
Normal
LGE: Inferior
RV insertion
+Chest Pain (2/10)
+Dyspnea (5/10)
 Peak VO2 58%
predicted
 Mild obstructive
defect
CT Pulmonary
Angiogram:
normal
10
20M
Team
Sport
1.3 months
Chest pain
Dyspnea
Palpitations
Lightheadedness
Exercise intolerance
Normal
Normal
Normal
Normal
+Chest Pain (8/10)
+Dyspnea (6/10)
+Lightheadedness
(2/10)
 Resting sinus tach.
 Moderate
obstructive defect
Patch Monitor:
normal
11
30F*
Endurance
3.0 months
Dyspnea
Cough
Exercise intolerance
Normal
Normal
Normal
+Dyspnea (7/10)
 Normal test
12
21M
Endurance
1.2 months
Dyspnea
Normal
Normal
Normal
--
+ Dyspnea (8/10)
 Low breathing
reserve
13
20M
Mixed
3.4 months
Chest pain
Normal
Normal
Normal
--
 Peak VO2 88%
predicted
 Moderately severe
obstructive defect
 Low breathing
reserve
14
21M
Team
Sport
1.8 months
Chest pain
Dyspnea
Exercise intolerance
Normal
Normal
--
LGE: Patchy
subepicardial
and
pericardial
+Chest Pain (3/10)
+Dyspnea (8/10)
 Mild obstructive
defect
 Low breathing
reserve
15
21M*
Mixed
7.3 months
Chest pain
Dyspnea
Palpitations
Normal
Normal
--
LGE: Inferior
RV insertion
+Chest Pain (6/10)
 Peak VO2 87%
predicted
Patch monitor:
normal
16
20F*
Team
Sport
5.9 months
Chest pain
Dyspnea
Palpitations
Normal
Sinus
Tach.
Normal
--
+Chest Pain (4/10)
+Dyspnea (9/10)
 Resting sinus tach.
Patch monitor:
normal
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi: 10.1136/bjsports-2021-105157
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 Blunted exercise
BP
 Mild obstructive
defect
Exercise intolerance
17
19F
Team
Sport
3.5 months
Chest pain
Dyspnea
Palpitations
Exercise intolerance
Normal
Normal
Normal
LGE: Inferior
RV insertion
+Chest Pain (4/10)
+Dyspnea (6/10)
 Normal test
18
20M
Team
Sport
1.5 months
Dyspnea
Palpitations
Exercise intolerance
Normal
Normal
Normal
--
 Peak VO2 79%
predicted
Patch monitor:
normal
19
19M*
Team
Sport
2.0 months
Dyspnea
Palpitations
Exercise intolerance
Normal
Normal
Normal
--
+Dyspnea (7/10)
 Peak VO2 65%
predicted
Patch monitor:
normal
20
20M
Team
Sport
1.2 months
Chest pain
Dyspnea
Exercise intolerance
Cough
Normal
Normal
Normal
Normal
+Dyspnea
 Normal test**
21
19F
Team
Sport
1.4 months
Chest pain
Palpitations
Exercise intolerance
Normal
Normal
Normal
Normal
+Chest Pain (2/10)
 Mild obstructive
defect
 Low breathing
reserve
Patch monitor:
normal
*Current (n=3) or childhood (n=2) asthma diagnosis
**n=2 tests on which spirometry on direct review was considered to reflect poor effort
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi: 10.1136/bjsports-2021-105157
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Supplemental Table 2: Longitudinal CPET Data in Post-COVID Athletes
First
Post-COVID
CPET
(n=13)
Second
Reference
Post-COVID Cohort
CPET
(n=26)
(n=13)
Testing Modality
Cycle ergometer
Treadmill
6 (46)
7 (54)
6 (46)
7 (54)
12 (46)
14 (54)
Vital Signs
Baseline HR (beats/min)
Peak HR (beats/min)
Percent Predicted
Heart Rate Recovery (beats/min)
Baseline SBP (mmHg)
Peak SBP (mmHg)
Baseline DBP (mmHg)
Peak DBP (mmHg)
Baseline O2 Saturation (%)
O2 Saturation (%) at Peak Exercise
81 ± 15
188 ± 9
95 ± 5
47 ± 13
122 ± 12
169 ± 21
75 ± 5
77 ± 5
98 ± 1
96 ± 2
75 ± 10*
183 ± 9*
93 ± 5*
46 ± 11
126 ± 16
172 ± 25
75 ± 7
75 ± 7
97 ± 1.5
95 ± 3
78 ± 14
186 ± 10
95 ± 4
47 ± 10
118 ± 11
168 ± 27
75 ± 8
67 ± 11^+
98 ± 1
96 ± 2
3.8 ± 1.0
88.6 ± 16.6
3 (23)
5.1 ± 1.0
100 ± 10
0.75 ± 0.12
4 (31)
4.1 ± 0.9
94.5 ± 12.7
1 (8)
5.1 ± 1.1
101.4 ± 11.8
0.79 ± 0.09
3 (23)
4.3 ± 0.9
97.3 ± 12.2
2 (8)
5.0 ± 1.1
97.3 ± 13.5
0.85 ± 0.06^+
1 (4)^+
1.16 ± 0.08
3.39 ± 0.69
46.7 ± 9.0
117 ± 36
1 (8)
38.2 ± 10.2
0.85 ± 0.23
18.0 ± 3.4
28.5 ± 3.9
24.5 ± 3.8
122 ± 34
17 ± 18
6 (46)
1.16 ± 0.07
3.62 ± 0.81*
49.0 ± 9.0
123 ± 38*
0 (0)
40.9 ± 9.0
0.77 ± 0.20*
19.7 ± 4.3*
27.3 ± 4.7
24.4 ± 4.3
123 ± 39
23 ± 20
3 (23)
1.16 ± 0.08
3.54 ±1.02
47.2 ± 10.6
114 ± 25
1 (4)
36.2 ± 11.0
0.83 ± 0.18
18.9 ± 5.2
28.7 ± 4.4
24.1 ± 3.4
126 ± 41
27 ± 15
3 (12)
Spirometry
Pre-Exercise FEV1 (L)
Percent Predicted (%)
Abnormal (Below 5th percentile)
Pre-Exercise FVC (L)
Percent Predicted (%)
Pre-Exercise FEV1/FVC
Abnormal (Below 5th percentile)
Gas Exchange
Respiratory Exchange Ratio
Peak
2 (L/min)
Peak
2 (ml/kg/min)
Percent Predicted (%)
Abnormal (<80% predicted)
2 at VT (ml/kg/min)
Chronotropic Index
Oxygen Pulse (ml/beat)
Total
/
2 slope
/
2 slope through VT
Peak
(L/min)
Breathing Reserve (%)*
Low Breathing Reserve (<10%)
*p<0.05 for post-COVID athletes baseline versus follow-up CPET. ^ p<0.05 for post-COVID athletes baseline versus
reference athletes. + p<0.05 for post-COVID athletes follow-up CPET versus reference athletes. HR: Heart Rate, bpm:
beat per minute, PP: peak percentage, HRR: Heart Rate Recovery, SBP: Systolic Blood Pressure, DBP: Diastolic Blood
Pressure, LLN: Lower limit of Normal, FEV1: Forced expiratory volume in the first second of forced breath, FVC:
Moulson N, et al. Br J Sports Med 2022;0:1–7. doi: 10.1136/bjsports-2021-105157
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forced vital capacity,
2: carbon dioxide production,
Ventilation, MVV: Maximum Voluntary Ventilation
Br J Sports Med
Oxygen consumption, VT: Ventilatory Threshold,
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Figure Legends
Supplement Figure 1. Generation of Reference Athlete Cohort Free of Cardiac Disease. Our database
contained 1837 CPETs in athlete patients, of which 566 were determined to healthy through the criteria above.
From amongst this healthy cohort of 566, athletes who had not had COVID-19 were identified that matched
with the post-COVID athletes as described in the Methods Supplement. CPET: cardiopulmonary exercise
testing. RER: respiratory exchange ratio. HR: heart rate.
Supplement Figure 2. Diagnostic Approach to Athletes with Persistent Cardiopulmonary Symptoms after COVID19.12
* For example, history and physical may reveal an obvious cause for symptoms suggestive of cardiopulmonary
origin such as costochondritis or pneumonia.
** ECG, Labs including HS-Troponin and TTE should be completed unless already performed as part of recent
return to play protocol. ^
T should e performed for evaluation of exertional symptoms unless a clinical
contraindication to exercise testing, such as active inflammatory heart disease, is present. ‡ Other clinically
indicated testing should be considered on a case-by-case basis. This may include ambulatory rhythm
monitoring, chest CT, and full pulmonary function testing including evaluation for exercise-induced
bronchoconstriction.
† High suspicion for inflammatory heart disease may e present despite normal initial testing if there is
persistent unexplained exertional chest pain or tightness, significant exertional intolerance, new palpitations or
syncope, and a short duration (< 3 months, particularly <1-2 months) since COVID-19 diagnosis, and no
alternative diagnosis (ex. pulmonary disease) evident on initial history, physical or diagnostic testing.13,14
PACS: Post-Acute COVID-19 Syndrome. ECG: electrocardiogram. TTE: transthoracic echocardiogram.
CPET: cardiopulmonary exercise testing. HS-Troponin: high sensitivity troponin. CMR: cardiac magnetic
resonance imaging. RTP: Return-to-play
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Supplement References:
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College Student-Athletes during the COVID-19 Pandemic 2021 [Available from:
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[published Online First: 2012/06/30]
12. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and Disqualification Recommendations for Competitive Athletes
With Cardiovascular Abnormalities: Task Force 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right
Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis: A Scientific Statement From the
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13. Phelan D, Kim JH, Drezner JA, et al. When to consider cardiac MRI in the evaluation of the competitive athlete after
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Moulson N, et al. Br J Sports Med 2022;0:1–7. doi: 10.1136/bjsports-2021-105157