Understanding Exertional Dyspnea and Exercise Intolerance in COVID-19

NCT04732663 | Completed

• 1 other identifier: Pro00107436
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

A novel corona virus emerged in 2019 causing Corona Virus Disease 2019 (covid-19). In one year more than 80 000 000 cases worldwide were documented. Some patients experience symptoms, specifically shortness of breath, long after the viral infection has passed. These patients are colloquially known as "Covid-19 Long-Haulers" and it is currently unknown why symptoms remain after infection. Shortness of breath and exercise intolerance may be caused by corona virus infection, covid-19 therapy, and reduced physical activity. Exercise intolerance may be due to lung, heart, blood vessel and muscle changes. During infection, the corona virus appears to cause lung blood vessel and gas exchange surface damage. Early reports show heart dysfunction, secondary to pulmonary blood vessel dysfunction or damage. Critically, no data is available on lung blood vessel function or cardiac function during exercise. Moreover, no data are available to link persistent symptoms to physiology parameters. To better understand symptom persistence in Covid-19, the investigators aim to measure exercise tolerance and heart and lung function in covid-19 survivors and compare them to covid-19 free controls.

Conditions

Covid19; Dyspnea

Keywords

DLCO; Pulmonary Capillary Blood Volume; VO2peak; Exercise Capacity; Cardiac Function; Impedance Cardiography; Echocardiography; Shortness of Breath; Ventilatory Efficiency; Lung Restriction

Outcome Measures

Primary Outcomes (3)

• Peak Oxygen Uptake (VO2peak)

  Staged cardiopulmonary exercise test

  Within 20-30 seconds of completion of trial

• Peak Cardiac Output (Qpeak)

  Impedance cardiography derived Qpeak from staged CPET

  Within 20-30 seconds of completion of trial

• Pulmonary Capillary Blood Volume (Vc)

  Multiple fraction of inspired oxygen DLCO derived pulmonary capillary blood volume at rest and during exercise.

  Averaged across trials

Secondary Outcomes (6)

• Ventilatory Efficiency (VE/VCO2)

  Averaged across trial

• Dyspnea

  Assessed every 2-minutes until completion of the exercise trial; anticipating ~10-14 minute tests

• Membrane Diffusion Capacity (Dm)

  Averaged across trials

• Pulmonary Artery Systolic Pressure (PASP)

  Assessed for five consecutive cardiac cycles and are measured in triplicate during the cardiac ultrasound trial

• Right Ventricular Function

  Assessed for five consecutive cardiac cycles and are measured in triplicate during the cardiac ultrasound trial

Other Outcomes (7)

• Physical Activity

  Step count averaged across 5 days

• Thigh Composition

  Assessed at rest and are measured in triplicate

• Frailty

  Assessed upon admission

Study Arms (3)

Persistently Symptomatic Covid-19 (PS-CoV)

PS-CoV will be defined as individuals with a history of molecular testing confirmed COVID-19 infection, recovered from acute infection but with ongoing symptoms (self-reported, pulmonary, cardiac, musculoskeletal or other symptoms) of at least 4 weeks' duration. Recovery from acute infection will be defined according to provincial health guidelines: at least 10 days' (14 in those hospitalized; 21 in those with immunocompromise) from onset of symptoms with at least 24 hours without a fever, without taking anti-pyretic medications and improvement of other symptoms.

Other: No Intervention

Recovered Covid-19

Recovered Covid-19 Survivors will be defined as individuals without complaint of a persisting covid-19 symptom. Recovered Covid-19 survivors will be matched to PS-CoV for age, sex, body mass index and time post corona virus infection.

Other: No Intervention

Control

Covid Naïve Controls will be defined as individuals who have no known history of covid-19. Control participants will be matched to PS-CoV for age, sex and body mass index.

Other: No Intervention

Interventions

No Intervention OTHER

Cross-sectional study, no intervention.

Control; Persistently Symptomatic Covid-19 (PS-CoV); Recovered Covid-19

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with or without a history of covid-19, with or without persistent symptoms.

You may qualify if:

• Covid-19/Symptom status as defined under each group.

You may not qualify if:

• Previous diagnosis of pulmonary hypertension
• Obesity (body mass index \>30 kg/m2)
• Absolute contraindication to exercise testing or an orthopedic limitation that may interfere with cardiopulmonary exercise testing

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Clinical Physiology Laboratory

Edmonton, Alberta, T6G2R3, Canada

Location

Related Publications (26)

• Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, Hosein Z, Padda I, Mangat J, Altaf M. Comorbidity and its Impact on Patients with COVID-19. SN Compr Clin Med. 2020;2(8):1069-1076. doi: 10.1007/s42399-020-00363-4. Epub 2020 Jun 25.

  PMID: 32838147 BACKGROUND

• Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.

  PMID: 32644129 BACKGROUND

• Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002 Mar 14;346(11):793-801. doi: 10.1056/NEJMoa011858.

  PMID: 11893790 BACKGROUND

• Quinn KL, Fralick M, Zipursky JS, Stall NM. Renin-angiotensin-aldosterone system inhibitors and COVID-19. CMAJ. 2020 May 19;192(20):E553-E554. doi: 10.1503/cmaj.200619. Epub 2020 Apr 24. No abstract available.

  PMID: 32332039 BACKGROUND

• Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020 Dec;29:100639. doi: 10.1016/j.eclinm.2020.100639. Epub 2020 Nov 20.

  PMID: 33251499 BACKGROUND

• Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, Jia JL, Li LM, Mao HL, Zhou XM, Luo H, Gao YF, Xu AG. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020 Aug;25:100463. doi: 10.1016/j.eclinm.2020.100463. Epub 2020 Jul 15.

  PMID: 32838236 BACKGROUND

• Dhawan RT, Gopalan D, Howard L, Vicente A, Park M, Manalan K, Wallner I, Marsden P, Dave S, Branley H, Russell G, Dharmarajah N, Kon OM. Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19. Lancet Respir Med. 2021 Jan;9(1):107-116. doi: 10.1016/S2213-2600(20)30407-0. Epub 2020 Nov 17.

  PMID: 33217366 BACKGROUND

• Merrill JT, Erkan D, Winakur J, James JA. Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications. Nat Rev Rheumatol. 2020 Oct;16(10):581-589. doi: 10.1038/s41584-020-0474-5. Epub 2020 Jul 30.

  PMID: 32733003 BACKGROUND

• Huang Y, Tan C, Wu J, Chen M, Wang Z, Luo L, Zhou X, Liu X, Huang X, Yuan S, Chen C, Gao F, Huang J, Shan H, Liu J. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res. 2020 Jun 29;21(1):163. doi: 10.1186/s12931-020-01429-6.

  PMID: 32600344 BACKGROUND

• Lang M, Som A, Carey D, Reid N, Mendoza DP, Flores EJ, Li MD, Shepard JO, Little BP. Pulmonary Vascular Manifestations of COVID-19 Pneumonia. Radiol Cardiothorac Imaging. 2020 Jun 18;2(3):e200277. doi: 10.1148/ryct.2020200277. eCollection 2020 Jun.

  PMID: 34036264 BACKGROUND

• Ackermann M, Mentzer SJ, Kolb M, Jonigk D. Inflammation and intussusceptive angiogenesis in COVID-19: everything in and out of flow. Eur Respir J. 2020 Nov 12;56(5):2003147. doi: 10.1183/13993003.03147-2020. Print 2020 Nov.

  PMID: 33008942 BACKGROUND

• Burel-Vandenbos F, Cardot-Leccia N, Passeron T. Pulmonary Vascular Pathology in Covid-19. N Engl J Med. 2020 Aug 27;383(9):886-887. doi: 10.1056/NEJMc2022068. Epub 2020 Jul 17. No abstract available.

  PMID: 32678531 BACKGROUND

• Sonnweber T, Sahanic S, Pizzini A, Luger A, Schwabl C, Sonnweber B, Kurz K, Koppelstatter S, Haschka D, Petzer V, Boehm A, Aichner M, Tymoszuk P, Lener D, Theurl M, Lorsbach-Kohler A, Tancevski A, Schapfl A, Schaber M, Hilbe R, Nairz M, Puchner B, Huttenberger D, Tschurtschenthaler C, Asshoff M, Peer A, Hartig F, Bellmann R, Joannidis M, Gollmann-Tepekoylu C, Holfeld J, Feuchtner G, Egger A, Hoermann G, Schroll A, Fritsche G, Wildner S, Bellmann-Weiler R, Kirchmair R, Helbok R, Prosch H, Rieder D, Trajanoski Z, Kronenberg F, Woll E, Weiss G, Widmann G, Loffler-Ragg J, Tancevski I. Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial. Eur Respir J. 2021 Apr 29;57(4):2003481. doi: 10.1183/13993003.03481-2020. Print 2021 Apr.

  PMID: 33303539 BACKGROUND

• Tedjasaputra V, Bouwsema MM, Stickland MK. Effect of aerobic fitness on capillary blood volume and diffusing membrane capacity responses to exercise. J Physiol. 2016 Aug 1;594(15):4359-70. doi: 10.1113/JP272037. Epub 2016 May 12.

  PMID: 26959808 BACKGROUND

• Tedjasaputra V, van Diepen S, Phillips DB, Wong EYL, Bhutani M, Michaelchuk WW, Bryan TL, Stickland MK. Pulmonary capillary blood volume response to exercise is diminished in mild chronic obstructive pulmonary disease. Respir Med. 2018 Dec;145:57-65. doi: 10.1016/j.rmed.2018.10.015. Epub 2018 Oct 19.

  PMID: 30509717 BACKGROUND

• Szekely Y, Lichter Y, Taieb P, Banai A, Hochstadt A, Merdler I, Gal Oz A, Rothschild E, Baruch G, Peri Y, Arbel Y, Topilsky Y. Spectrum of Cardiac Manifestations in COVID-19: A Systematic Echocardiographic Study. Circulation. 2020 Jul 28;142(4):342-353. doi: 10.1161/CIRCULATIONAHA.120.047971. Epub 2020 May 29.

  PMID: 32469253 BACKGROUND

• Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5.

  PMID: 32139904 BACKGROUND

• Li Y, Li H, Zhu S, Xie Y, Wang B, He L, Zhang D, Zhang Y, Yuan H, Wu C, Sun W, Zhang Y, Li M, Cui L, Cai Y, Wang J, Yang Y, Lv Q, Zhang L, Xie M. Prognostic Value of Right Ventricular Longitudinal Strain in Patients With COVID-19. JACC Cardiovasc Imaging. 2020 Nov;13(11):2287-2299. doi: 10.1016/j.jcmg.2020.04.014. Epub 2020 Apr 28.

  PMID: 32654963 BACKGROUND

• Oliveira RKF, Faria-Urbina M, Maron BA, Santos M, Waxman AB, Systrom DM. Functional impact of exercise pulmonary hypertension in patients with borderline resting pulmonary arterial pressure. Pulm Circ. 2017 Jul-Sep;7(3):654-665. doi: 10.1177/2045893217709025. Epub 2017 Jun 8.

  PMID: 28895507 BACKGROUND

• Vonk Noordegraaf A, Galie N. The role of the right ventricle in pulmonary arterial hypertension. Eur Respir Rev. 2011 Dec;20(122):243-53. doi: 10.1183/09059180.00006511.

  PMID: 22130817 BACKGROUND

• D'Alto M, Marra AM, Severino S, Salzano A, Romeo E, De Rosa R, Stagnaro FM, Pagnano G, Verde R, Murino P, Farro A, Ciccarelli G, Vargas M, Fiorentino G, Servillo G, Gentile I, Corcione A, Cittadini A, Naeije R, Golino P. Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS. Crit Care. 2020 Nov 30;24(1):670. doi: 10.1186/s13054-020-03385-5.

  PMID: 33256813 BACKGROUND

• Gualtieri P, Falcone C, Romano L, Macheda S, Correale P, Arciello P, Polimeni N, Lorenzo A. Body Composition Findings by Computed Tomography in SARS-CoV-2 Patients: Increased Risk of Muscle Wasting in Obesity. Int J Mol Sci. 2020 Jun 30;21(13):4670. doi: 10.3390/ijms21134670.

  PMID: 32630032 BACKGROUND

• Hewitt J, Carter B, Vilches-Moraga A, Quinn TJ, Braude P, Verduri A, Pearce L, Stechman M, Short R, Price A, Collins JT, Bruce E, Einarsson A, Rickard F, Mitchell E, Holloway M, Hesford J, Barlow-Pay F, Clini E, Myint PK, Moug SJ, McCarthy K; COPE Study Collaborators. The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study. Lancet Public Health. 2020 Aug;5(8):e444-e451. doi: 10.1016/S2468-2667(20)30146-8. Epub 2020 Jun 30.

  PMID: 32619408 BACKGROUND

• Ma Y, Hou L, Yang X, Huang Z, Yang X, Zhao N, He M, Shi Y, Kang Y, Yue J, Wu C. The association between frailty and severe disease among COVID-19 patients aged over 60 years in China: a prospective cohort study. BMC Med. 2020 Sep 7;18(1):274. doi: 10.1186/s12916-020-01761-0.

  PMID: 32892742 BACKGROUND

• McGuire DK, Levine BD, Williamson JW, Snell PG, Blomqvist CG, Saltin B, Mitchell JH. A 30-year follow-up of the Dallas Bedrest and Training Study: II. Effect of age on cardiovascular adaptation to exercise training. Circulation. 2001 Sep 18;104(12):1358-66.

  PMID: 11560850 BACKGROUND

• Ferretti G, Antonutto G, Denis C, Hoppeler H, Minetti AE, Narici MV, Desplanches D. The interplay of central and peripheral factors in limiting maximal O2 consumption in man after prolonged bed rest. J Physiol. 1997 Jun 15;501 ( Pt 3)(Pt 3):677-86. doi: 10.1111/j.1469-7793.1997.677bm.x.

  PMID: 9218227 BACKGROUND

MeSH Terms

Conditions

COVID-19; Dyspnea

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael K Stickland, Ph.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 1, 2021
• Study Start: March 4, 2021
• Primary Completion: October 1, 2021
• Study Completion: May 6, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)