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Case Reports: Findings that shed new light on the possible pathogenesis of a disease
Reduced athletic performance post-COVID-19 is associated with reduced anaerobic threshold
  1. Robert M Barker-Davies1,
  2. Peter Ladlow1,
  3. Rebecca Chamley2,
  4. Edward Nicol3 and
  5. David A Holdsworth2
  1. 1Academic Department of Military Rehabilitation, Loughborough, UK
  2. 2Oxford University Hospitals NHS Trust, Oxford, UK
  3. 3Department of Cardiology, Royal Brompton Hospital, London, UK
  1. Correspondence to Dr David A Holdsworth; david.holdsworth{at}nhs.net

Abstract

Detailed characterisation of cardiopulmonary limitations in patients post-COVID-19 is currently limited, particularly in elite athletes. A male elite distance runner in his late 30s experienced chest pain following confirmed COVID-19. He underwent cardiopulmonary exercise testing (CPET) at 5 months postacute illness. Subjective exercise tolerance was reduced compared with normal, he described inability to ‘kick’ (rapidly accelerate). His CPET was compared with an identical protocol 15 months prior to COVID-19. While supranormal maximal oxygen uptake was maintained (155% of peak predicted V̇O2) anaerobic threshold (AT), a better predictor of endurance performance, reduced from 84% to 71% predicted peak V̇O2 maximum. Likewise, fat oxidation at AT reduced by 21%, from 0.35 to 0.28 g/min. Focusing exclusively on V̇O2 maximum risks missing an impairment of oxidative metabolism. Reduced AT suggests a peripheral disorder of aerobic metabolism. This finding may result from virally mediated mitochondrial dysfunction beyond normal ‘deconditioning’, associated with impaired fat oxidation.

  • COVID-19
  • Rehabilitation medicine
  • Sports and exercise medicine
  • Cardiovascular medicine

https://doi.org/10.1136/bcr-2022-250191

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    Background

    Following an apparently mild initial COVID-19 presentation patients frequently suffer prolonged symptoms such as fatigue, breathlessness and chest pain.1–3 These symptoms, commonly experienced post-COVID-19, are also hallmark symptoms of myocarditis, which has been implicated following COVID-19.4 Myocarditis has been implicated in 10% of cases of sudden cardiac death.5 Lung fibrosis and pulmonary embolism have also been associated with COVID-19 and can cause similar symptoms.6 7 Other coronavirus infections, such as severe acute respiratory syndrome, have been known to cause debilitating postviral fatigue at long-term follow-up.8 Breathlessness can also be caused by health anxiety which is understandable given media reporting, and the pervasive social impact of COVID-19. Anxiety can be a driver of a dysfunctional breathing pattern.9

    Distinguishing between patients suffering from significant cardiopulmonary pathology, those suffering from a typical postviral fatigue syndrome or dysfunctional breathing can be challenging. One method to exclude cardiopulmonary pathology is a maximal effort test such as the multistage fitness test as a predictor of V̇O2 maximum.10 However, the results of such tests may still be supranormal in a trained athletic population when compared with ‘normal’ reference data. The aetiology of postviral fatigue is complex, involving multiple mechanisms including neuroinflammation, autoantibodies, dysautonomia and abnormal energy metabolism.11 As both the acute presentation and subsequent function at follow-up cannot reliably determine aetiology, an objective characterisation of the physiological processes that determine athletic performance is very useful.

    Cardiopulmonary exercise testing (CPET) can objectively characterise the limits of human performance. Using breath by breath analysis CPET can help rule out cardiopulmonary pathology and, in addition to objective measures of peak capacity and anaerobic threshold (AT), provide measures inversely correlated with ventilatory efficiency (V̇E/VCO2) and correlated with the stroke volume (V̇O2/HR, the O2 pulse).12 CPET can also offer insight into the postviral mechanisms for reduced exercise tolerance, particularly in relation to dysautonomia (characterised by heart rate (HR) and blood pressure responses) and impaired oxidative energy metabolism (AT and oxygen uptake efficiency slope).13 14 The AT is a reliable predictor of endurance performance.15 Above the AT a steady-state acid-base balance cannot be maintained, limiting prolonged exercise.16 This report compares an identical CPET protocol obtained pre-COVID-19 and post-COVID-19 infection highlighting differences that give insight into the aetiology of post-COVID-19 (long COVID) syndromes in an elite athlete.

    Case presentation

    A male elite distance runner in his late 30s became unwell eleven months after the onset of the COVID-19 pandemic. Initially, he experienced headache. Over the next 3 days, he developed a dry persistent cough, shortness of breath, fever, fatigue and sore throat. PCR nasal/throat swab taken on day one was positive for COVID-19. He had not yet been vaccinated against COVID-19. These acute symptoms resolved by day 6. Left-sided chest pain persisted on exertion with three distinct episodes. On day 8, he had an episode of left side chest pain, which was neither pleuritic nor positional. He consulted his general practitioner (GP) by telephone describing laboured breathing and a burning sensation in the chest without radiation to the arm or jaw. A cautious plan to self-manage symptoms at home was made with clear direction to seek further medical help in the case of deterioration. The second episode followed carrying bags on day 12, lasted overnight and resulted in emergency department (ED) attendance. Troponin was reported as negative and the ECG as non-ischaemic. A third episode occurred following a run on day 28 and resulted in NHS 111 call and ED attendance with negative troponin and a non-ischaemic ECG.

    Blood tests taken at day 31 were normal, with the exception of a bilirubin of 38 µmol/L (known Gilbert’s syndrome), and included full blood count (FBC), urea and electrolytes (UE), liver function tests (LFTs), thyroid function tests (TFTs), C reactive protein (CRP), calcium, serum protein. A cardiology opinion at 6 weeks encouraged him to continue running, pending review of a planned 5-day Holter monitor, echocardiogram and exercise test. The echocardiogram at 12 weeks showed a structurally normal heart with left atrial dilatation attributed to athletic adaptation. The Bruce protocol exercise test lasted 21 min with an appropriate rise in HR and blood pressure, stopped due to completion of the protocol. There was no associated chest pain. A 24-hour Holter monitor ECG demonstrated sinus rhythm throughout, with bradycardia and no arrythmia. The burden of supraventricular and ventricular ectopics was less than 1%. A rehabilitation assessment by video teleconference at 12 weeks noted that his chest pain had resolved. A review by his GP at 16 weeks noted that he was able to run up to 10 miles without chest pain.

    Twenty-four months prior to the onset of COVID-19 he had undergone a cardiac ablation for a left-sided accessory pathway (retrograde p wave). Due to a return of palpitations, he was further investigated with a cardiac MRI, which showed athletic adaptation (left ventricular ejection fraction (LVEF) of 50%) and no evidence of cardiomyopathy. CPET demonstrated supranormal function (discussed further below). On CPET the peak V̇O2/HR (‘oxygen pulse’—correlated with stroke volume) was 154% of the predicted value. This oxygen pulse confirms that the slightly low LVEF at rest is likely to result from athletic adaptation.17 A further diagnostic electrophysiology study demonstrated no persistence of an accessory pathway. After a period of 8 months free from palpitations, he was discharged from cardiology follow-up 4 months prior to contracting COVID-19. The preceding treatment for this accessory pathway was curative and would not account for any ongoing cardiopulmonary limitation.

    He presented for cardiopulmonary review and testing at 5 months as part of an occupationally focused post-COVID-19 service with the aim of removing all restrictions to his role.18 He had a normal cardiorespiratory exam, with the exception of expected regular bradycardia and sinus arrhythmia his ECG demonstrated sinus bradycardia. A summary timeline is included as table 1.

    View this table:
    Table 1

    Timeline

    Investigations

    The following investigations were undertaken 5 months post onset of COVID-19. Patient-reported outcome measures with reference ranges are presented in table 2.

    View this table:
    Table 2

    Patient-reported outcome measures with reference ranges at 5 months post onset of COVID-19

    Blood tests including FBC, UE, LFTs (with exception of bilirubin), HBA1C, serum iron, ferritin, vitamin D, TFTs and CRP were normal. Creatine kinase was raised at 480 U/L as was Bilirubin at 46 µmol/L (known Gilbert’s syndrome).

    Spirometry was normal with an FEV1 of 4.47 L (120% predicted), FVC of 5.97 (131% predicted) and an FEV1/FVC ratio of 0.75.

    CPET findings are presented alongside the test 15 months before contracting COVID-19 (figure 1A). Both tests were conducted under the care of the corresponding author using an identical exercise protocol, equipment, calorimeter and processing software. A ramp protocol to maximal voluntary effort was performed on an electromagnetically braked upright cycle ergometer (Lode Corival, The Netherlands). Following a 2 min resting period, 2 min of unloaded pedalling preceded incremental resistance starting at 25W with a ramp of 30 W/minute. Tidal volume and breathing frequency were measured by indirect calorimetry (Metalyzer 3B Cortex Biophysik, Leipzig, Germany). Maximal testing was defined as a peak relative energy ratio ≥1.10 and/or plateau in oxygen uptake (≥ 20 s) despite increasing workload. Fat oxidation was calculated according to the method described by Jeukendrup and Wallis.19

    Figure 1
    Figure 1

    Cardiopulmonary exercise test nine-panel plots. (A) 15 months prior and (B) 5 months post-COVID-19 infection in an elite distance runner. While the V̇O2 maximum is preserved at around 4.0 L (blue line top right graph), anaerobic threshold (first solid vertical green line on each graph) occurs earlier in the second test. (B) 8 min and 39 s into the protocol and <2.0 L V̇O2 compared with the first test (A) at 9 min and 42 s and >2.0 L V̇O2.

    The second test 5 months after acute COVID-19 demonstrated a similar V̇O2 peak of 155% predicted (previously 153%) but reduced AT occurring at 71% peak predicted V̇O2 (previously 84%) (figure 1B). The reduction in V̇O2 at AT was associated with a reduction in external work by 27 W, from 189 W to 162 W (a reduction of 14%) (table 3). No abnormalities were detected on 12-lead ECG monitoring.

    View this table:
    Table 3

    Cardiopulmonary exercise test (CPET) outcomes 15 months prior and 5 months post COVID-19 diagnosis

    Differential diagnosis

    The patient’s acute illness occurred at a time of high prevalence of COVID-19 in the UK, following contact with a confirmed case in the preceding 3 days. His presentation included 5 of the 10 most common acute symptoms.20 The diagnosis was confirmed with a positive PCR test. It remains important to consider any alternative and possibly co-existing explanations for fatigue, reduced exercise performance and headache. A diagnosis of acute myocarditis was ruled out by a negative troponin and unconcerning ECG. Pericarditis is not supported in the history in that his chest pain was not positional and there were no typical changes on ECG. Pulmonary embolism and lung fibrosis are unlikely based on the ECG, SpO2 and ventilatory efficiency (V̇E/VCO2 slope) on CPET. However, it is worth clarifying a chest radiograph, high-resolution CT scan or CT pulmonary angiogram was not performed. This was a clinical decision based on emerging evidence and applying principles of resource management and reduction in ionising radiation. The current authors reported on an initial cohort of 113 post-COVID-19 patients of whom 6 had evidence of lung fibrosis on CT. In that study CPET in combination with blood gas testing immediately on cessation of exercise, could be reliably used to exclude significant pathology. A normal V̇O2 max and normal V̇E/VCO2 slope, as demonstrated in this case using an identical protocol, were used as assessment criteria.21 The history and blood tests are not consistent with an alternate infectious disease such as infectious mononucleosis, Q-fever or Lyme disease. Blood tests also excluded diabetes and thyroid dysfunction. His LFTs were normal with the exception of a mild bilirubin rise in the context of known Gilbert’s syndrome. There was no deficiency of vitamin D or iron stores.

    Treatment

    The patient self-isolated following the positive PCR test and continued to work from home. His initial treatment was limited to cautious observation with appropriate safety net processes. No prescriptions of medication were made. He returned to work on day 18 consisting of reduced working hours in a predominantly office-based role. Return to work did not provoke symptoms. He was given initial advice by his GP to avoid cardiovascular exercise pending review by the cardiologist who had seen him previously for ablation of the accessory pathway. He resumed a base of steady state aerobic training, initially with increased rest periods from week three post initial infection (see Patient’s perspective below). He delayed the reintroduction of interval training as a result of the ongoing symptoms to around 3 months post infection. Pre-COVID-19 and post-COVID-19, he had a training strategy of pacing runs to a set HR of 138 beats per minute (bpm). After week 7, he found this strategy enabled him to avoid exacerbating symptoms of fatigue, headache and palpitations. The gradual improvement in pace is demonstrated in figure 2. After 4 months, he was able to increase the amount of interval training at higher (than 138 bpm) HRs. After 7 months he felt his ‘kick’ was back to normal and he was able to run steeplechase races, in which acceleration and variation in pace is required to negotiate barriers, without symptoms.

    Figure 2
    Figure 2

    Running pace post-COVID-19 in an elite distance runner at a constant of heart rate of 138 sustained for four miles compared to baseline pre-COVID-19 pace (horizontal blue line). The acute symptoms lasted until day 6, three distinct episodes of chest pain are indicated by the vertical dotted (red) lines. The date of the cardiopulmonary exercise test (CPET) is annotated at 19 weeks.

    Outcome and follow-up

    Following the review 5 months postinfection, all occupational restrictions were removed and the patient was discharged from follow-up. Eleven months after contracting COVID-19, he ran 33 min and 3 s for 10 km, a time 1 min faster than run 17 months prior to his acute illness.

    Discussion

    This case describes the preserved V̇O2 maximum but reduced AT of an elite distance runner 5 months after COVID-19 infection. This earlier anaerobic transition was associated with a 27 W reduction in workload and a 13% reduction in oxygen uptake. In performance terms, this represents a considerable deficit in his function and explains his inability to ‘kick’ (rapidly increase pace). While the absolute values of his CPET fall well within ‘normal’ limits, the relative changes for him as an individual and the associated symptoms are highly significant and offer insight into the pathophysiology of post-COVID-19 exercise limitation and for post-COVID-19 syndrome more broadly.

    One simple explanation for the findings is that the effects of deconditioning caused by the enforced rest are known to be more pronounced on AT in endurance athletes than in sedentary individuals.22 Indeed, deconditioning has been cited as the cause for exercise limitation in two CPET studies conducted at 3 months following acute COVID-19 infection.23 24 However, in this case, the stroke volume and cardiac output, which would be anticipated to decrease with deconditioning,25 are preserved. This is demonstrated by the near-identical values for oxygen pulse (V̇O2/HR) and peak HR pre and post-COVID-19 (table 3). It is therefore worth considering alternative mechanisms to explain prolonged exercise limitation in this very fit individual recovering from COVID-19.

    Reduced oxygen uptake during exercise has been demonstrated previously in patients with chronic fatigue syndrome (CFS).13 Repeat testing on two consecutive days, revealed that workload and oxygen uptake at AT were much more negatively impacted than peak values over consecutive days (intraclass correlation coefficient2,1 0.498 (0.254–0.682) and 0.426 (0.167–0.630) for workload and VO2 at AT vs 0.871 (0.784–0.924) and 0.801 (0.676–0.882) for workload and V̇O2 at peak).26 Symptoms of CFS are similar to those described by post-COVID-19 patients including fatigue and postexertional malaise.3 Mitochondrial dysfunction has been described in COVID-19 patients and is associated with increased dependence on glucose pathways and decreased ability to use fatty acids as the predominant fuel substrate.27 The calorimetry findings in this athlete are consistent with an impairment of fat metabolism and an earlier transition to anaerobic glycolysis. This is demonstrated by a 21% reduction in fat oxidation at the AT (table 3), which could also explain the earlier AT. Conversely, V̇O2 peak, which relies much more on cytosolic carbohydrate metabolism (glycolysis) is relatively preserved. Operating at a given workload with a relatively higher ratio of anaerobic to aerobic metabolism could also explain a reduced capacity for a sudden increase in power output.28 The lack of ability of an elite athlete to ‘kick’ might be considered akin to the general population struggling in their performance of more routine activities. Inefficiency of aerobic fat metabolism might also shed light on the sexual asymmetry of post-COVID-19 symptoms, which are more common in women. It is known that women are more dependent than men on fat oxidation for submaximal activity.28 A peripheral oxygen use problem was also the conclusion of a recent invasive CPET study, which included radial artery and right heart catheterisation to estimate cardiac output and to directly measure peripheral oxygen use in patients 11 months post-COVID-19. This study demonstrated that cardiac output did not differ from controls and that reduced oxygen uptake (V̇O2) was explained by reduced peripheral oxygen extraction rather than any cardiopulmonary pathology.25 The same conclusion was reached in a cohort assessed immediately prior to hospital discharge following COVID-19, which measured cardiac output non-invasively using pulsed wave Doppler of the left ventricular outflow tract in concert with CPET.29 Given the potential mechanisms involved, as described above, athletes experiencing similar problems following COVID-19 should be encouraged to titrate their training regimens to avoid symptom exacerbation. Such an approach has been shown to reduce postexercise symptom exacerbation in a post-COVID-19 cohort.30

    The strengths of this work are the availability of CPET data from an identical protocol and equipment shortly before and after COVID-19 illness and the routine, prospective collection of the patient’s own training data, which reduces recall bias. Naturally, while key insight may be gained from careful study of a single individual, extrapolation of any conclusions must be exercised with caution.

    Patient’s perspective

    I attempted my first run 22 days after catching COVID-19, a 4 mile run at my aerobic 138bpm heart rate. Before COVID-19 this would be done in around 28 min (7 min mile pace), I ran 35 mins (8:45 mile pace). After the run and the following few days, I found myself feeling quite unwell again, fatigued, headaches and some mild heart symptoms (palpitations, mild chest discomfort and arrhythmia straight after my run). I felt that poorly after my first few runs that I had to have large gaps in-between (6–7 days), before building up gradually still running at the 138bpm. It wasn’t until day 52 that progress was being made, my times started to consistently increase in an upward trajectory. I still had abnormalities: my heart-rate would jump on my runs or stall at a low heart rate for an age before suddenly shooting up. Straight after my runs I found my heart-rate would stay fast while standing still and wouldn’t recover, then suddenly like a switch it would revert to a slow rhythm.

    During the 3 months after contracting COVID-19, I continued with mild symptoms and slowly increased my aerobic fitness. I attempted my first 2 mile tempo run on day 102 and discovered a big drop off on the second mile pace, this was an issue that continued with my first competitions.

    Running my first race, a 3 km Steeplechase on day 115, I found the second half of the run a real struggle. My pace would considerably drop off and my breathing was harder than normal. I continued with the same event knocking off roughly 10 s each race every 3 weeks, but found I still lacked power over the second half and had no sprint finish. I increased my fitness, which also related to the increase in aerobic fitness and times during my 4 mile 138bpm runs.

    32 weeks after the initial infection I ran 27:17 for the 4 mile run, 6:48 mile pace, then 2 days later I finally ran for the England Masters 35–39 age category in the Richmond RUNFEST half marathon (Race postponed twice due to COVID-19). Delighted to finish second for my age category and running 1 hour 13 min 38 s, I was only roughly 90 s slower than my qualifying time 18 months prior and hope to continue improving back to my pre-COVID-19 fitness.

    Learning points

    • Fatigue, chest pain and reduced exercise tolerance are common findings in patients following COVID-19. They may be accounted for by organ pathology in the heart and lung; postviral fatigue or health anxiety.

    • Reduced athletic performance may be explained by a premature anaerobic threshold and decreased ‘exercise efficiency’, which may be masked by relatively preserved maximum oxygen uptake.

    • Cardiopulmonary exercise testing is a safe, objective, non-invasive technique to provide detailed insight into the presence and mechanisms of functional limitation.

    Ethics statements

    Patient consent for publication

    References

    1. ↵
      1. O’Sullivan O,
      2. Barker-Davies RM,
      3. Thompson K, et al
      . Rehabilitation post-COVID-19: cross-sectional observations using the stanford hall remote assessment tool. BMJ Mil Health 2021:bmjmilitary–2021. doi:10.1136/bmjmilitary-2021-001856
    2. ↵
      1. Taquet M,
      2. Dercon Q,
      3. Luciano S, et al
      . Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19. PLOS Med 2021;18:e1003773. doi:10.1371/journal.pmed.1003773
    3. ↵
      1. Davis HE,
      2. Assaf GS,
      3. McCorkell L, et al
      . Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine 2021;38:101019. doi:10.1016/j.eclinm.2021.101019
      OpenUrl
    4. ↵
      1. Puntmann VO,
      2. Carerj ML,
      3. Wieters I, et al
      . Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:1265–73. doi:10.1001/jamacardio.2020.3557
      OpenUrl
    5. ↵
      1. Tschöpe C,
      2. Ammirati E,
      3. Bozkurt B, et al
      . Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol 2021;18:169–93. doi:10.1038/s41569-020-00435-x
      OpenUrlPubMed
    6. ↵
      1. Zou J-N,
      2. Sun L,
      3. Wang B-R, et al
      . The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT. PLOS ONE 2021;16:e0248957. doi:10.1371/journal.pone.0248957
    7. ↵
      1. Sakr Y,
      2. Giovini M,
      3. Leone M, et al
      . Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review. Ann Intensive Care 2020;10:124. doi:10.1186/s13613-020-00741-0
    8. ↵
      1. Lam MH-B,
      2. Wing Y-K,
      3. Yu MW-M, et al
      . Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up. Arch Intern Med 2009;169:2142–7. doi:10.1001/archinternmed.2009.384
      OpenUrlCrossRefPubMed
    9. ↵
      1. Boulding R,
      2. Stacey R,
      3. Niven R, et al
      . Dysfunctional breathing: a review of the literature and proposal for classification. Eur Respir Rev 2016;25:287–94. doi:10.1183/16000617.0088-2015
      OpenUrlAbstract/FREE Full Text
    10. ↵
      1. Ramsbottom R,
      2. Brewer J,
      3. Williams C
      . A progressive shuttle run test to estimate maximal oxygen uptake. Br J Sports Med 1988;22:141–4. doi:10.1136/bjsm.22.4.141
      OpenUrlAbstract/FREE Full Text
    11. ↵
      1. Komaroff AL,
      2. Lipkin WI
      . Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med 2021;27:895–906. doi:10.1016/j.molmed.2021.06.002
      OpenUrlCrossRef
    12. ↵
      1. Albouaini K,
      2. Egred M,
      3. Alahmar A, et al
      . Cardiopulmonary exercise testing and its application. Heart 2007;93:1285–92. doi:10.1136/hrt.2007.121558
      OpenUrlAbstract/FREE Full Text
    13. ↵
      1. Vermeulen RCW,
      2. Vermeulen van Eck IWG
      . Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. J Transl Med 2014;12:20. doi:10.1186/1479-5876-12-20
    14. ↵
      1. Jouven X,
      2. Empana J-P,
      3. Schwartz PJ, et al
      . Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005;352:1951–8. doi:10.1056/NEJMoa043012
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      1. Tanaka K,
      2. Matsuura Y,
      3. Matsuzaka A, et al
      . A longitudinal assessment of anaerobic threshold and distance-running performance. Medicine & Science in Sports & Exercise 1984;16:278. doi:10.1249/00005768-198406000-00014
      OpenUrl
    16. ↵
      1. Zoladz JA,
      2. Sargeant AJ,
      3. Emmerich J, et al
      . Changes in acid-base status of marathon runners during an incremental field test. Relationship to mean competitive marathon velocity. Eur J Appl Physiol Occup Physiol 1993;67:71–6. doi:10.1007/BF00377708
      OpenUrlCrossRefPubMedWeb of Science
    17. ↵
      1. Millar LM,
      2. Fanton Z,
      3. Finocchiaro G, et al
      . Differentiation between athlete’s heart and dilated cardiomyopathy in athletic individuals. Heart 2020;106:1059–65. doi:10.1136/heartjnl-2019-316147
      OpenUrlAbstract/FREE Full Text
    18. ↵
      1. O’Sullivan O,
      2. Barker-Davies R,
      3. Chamley R, et al
      . Defence medical rehabilitation centre (DMRC) COVID-19 recovery service. BMJ Mil Health 2021:e001681. doi:10.1136/bmjmilitary-2020-001681
    19. ↵
      1. Jeukendrup AE,
      2. Wallis GA
      . Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int J Sports Med 2005;26 Suppl 1(S 1):S28–37. doi:10.1055/s-2004-830512
      OpenUrlPubMed
    20. ↵
      1. Menni C,
      2. Valdes AM,
      3. Freidin MB, et al
      . Real-Time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020;26:1037–40. doi:10.1038/s41591-020-0916-2
      OpenUrlCrossRefPubMed
    21. ↵
      1. Holdsworth DA,
      2. Barker-Davies RM,
      3. Chamley RR, et al
      . Cardiopulmonary exercise testing excludes significant disease in patients recovering from COVID-19. BMJ Mil Health 2022:e002193. doi:10.1136/military-2022-002193
    22. ↵
      1. Smorawiński J,
      2. Nazar K,
      3. Kaciuba-Uscilko H, et al
      . Effects of 3-day bed rest on physiological responses to graded exercise in athletes and sedentary men. J Appl Physiol (1985) 2001;91:249–57. doi:10.1152/jappl.2001.91.1.249
      OpenUrlPubMedWeb of Science
    23. ↵
      1. Rinaldo RF,
      2. Mondoni M,
      3. Parazzini EM, et al
      . Deconditioning as main mechanism of impaired exercise response in COVID-19 survivors. Eur Respir J 2021;58:2100870. doi:10.1183/13993003.00870-2021
    24. ↵
      1. Skjørten I,
      2. Ankerstjerne OAW,
      3. Trebinjac D, et al
      . Cardiopulmonary exercise capacity and limitations 3 months after COVID-19 hospitalisation. Eur Respir J 2021;58:2100996. doi:10.1183/13993003.00996-2021
    25. ↵
      1. Singh I,
      2. Joseph P,
      3. Heerdt PM, et al
      . Persistent exertional intolerance after COVID-19: insights from invasive cardiopulmonary exercise testing. Chest 2022;161:54–63. doi:10.1016/j.chest.2021.08.010
      OpenUrlPubMed
    26. ↵
      1. Davenport TE,
      2. Stevens SR,
      3. Stevens J, et al
      . Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic Encephalomyelitis/Chronic fatigue syndrome. Work 2020;66:247–56. doi:10.3233/WOR-203170
      OpenUrl
    27. ↵
      1. Ajaz S,
      2. McPhail MJ,
      3. Singh KK, et al
      . Mitochondrial metabolic manipulation by SARS-cov-2 in peripheral blood mononuclear cells of patients with COVID-19. Am J Physiol Cell Physiol 2021;320:C57–65. doi:10.1152/ajpcell.00426.2020
      OpenUrlCrossRef
    28. ↵
      1. Hargreaves M,
      2. Spriet LL
      . Skeletal muscle energy metabolism during exercise. Nat Metab 2020;2:817–28. doi:10.1038/s42255-020-0251-4
      OpenUrl
    29. ↵
      1. Baratto C,
      2. Caravita S,
      3. Faini A, et al
      . Impact of COVID-19 on exercise pathophysiology: a combined cardiopulmonary and echocardiographic exercise study. J Appl Physiol (1985) 2021;130:1470–8. doi:10.1152/japplphysiol.00710.2020
      OpenUrlCrossRefPubMed
    30. ↵
      1. Parker M,
      2. Sawant HB,
      3. Flannery T, et al
      . Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome. J Med Virol 2023;95:e28373. doi:10.1002/jmv.28373

    Footnotes

    • Contributors RMB-D and DH conceived the idea for the manuscript. RMB-D, DH, and PL collected and processed the raw data. RMB-D wrote the first draft and produced figures 1 and 2. DH and EN edited and completed the first round of manuscript review. DH and EN clinically managed the case and provided clinical and academic supervision.All authors reviewed and edited the final manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.