Pulmonary Vascular Dysfunction as a Cause of Persistent Exertional Dyspnea After Coronavirus Disease (COVID-19)

Recruiting

• Conditions: COVID-19
• Interventions: Other: pulmonary vascular function; Other: pulmonary vascular dysfunction

• Registration Number: NCT05374577
• Lead Sponsor: University of Giessen

Brief Summary

To identify pulmonary vascular disease in post/long-COVID-19 patients as a cause of dyspnea/exercise limitation and to differentiate it from other causes of dyspnea

Detailed Description

The aim is to identify pulmonary vascular disease in post/long-COVID-19 patients as a cause of dyspnea/exercise limitation and to differentiate it from other causes of dyspnea (muscular, left cardiac, psychological, deconditioning-related causes) by investigating ventilation-perfusion (V/Q) mismatch and (exercise-induced) pulmonary hypertension (PH) or right heart dysfunction.

Study Timeline

• Study Start: 2022-04-15
• Study First Submitted: 2022-04-29
• Study First Submitted QC: 2022-05-13
• Study First Posted: 2022-05-16
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-08
• Primary Completion: 2025-03
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Age ≥ 18 years, patients with a suspected diagnosis of post/long-COVID-19 syndrome who present to our pneumology or infectious disease outpatient clinic or corresponding ward from the start of the study and whose SARS-CoV-2 infection was diagnosed at least 3 and not longer than 18 months prior to presentation
• Patients at least 3 and not longer than 18 months after a SARS-CoV-2 infection without post/long-COVID-19 syndrome who present to our post-infection outpatient clinic for follow-up

Exclusion Criteria

• Patients who refuse to participate in the study
• Severe underlying chronic pulmonary, cardiac, or systemic disease (e.g., Chronic obstructive pulmonary disease (COPD), severe heart failure, neuromuscular disease) that was diagnosed prior to acute COVID-19 disease and whose progression appears likely as the cause of dyspnea
• Other non pneumologic causes of dyspnea (e.g., hemoglobin < 100 g/L)
• Unstable or acute disease (e.g., acute infection, acute renal failure, acute coronary syndrome)
• Inability to perform spiroergometry, including transient orthopedic problems, contraindications to central venous and arterial catheter placement (e.g., severe bleeding tendency).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients without post/long-COVID-19 Syndrome	pulmonary vascular function	Patients at least 3 months after a SARS-CoV-2 infection (symptomatic or asymptomatic) without post/long-COVID-19.
Patients with a suspected diagnosis of post/long-COVID-19	pulmonary vascular dysfunction	Patients with a suspected post-COVID-19 syndrome or a long-COVID-19 syndrome at least 3 months after severe acute respiratory syndrome coronavirus(CoV) type 2 (SARS-CoV-2) infection (symptomatic or asymptomatic)

Primary Outcome Measures

Name	Time	Method
Echocardiographic right heart parameters - pulmonary arterial systolic pressure (PASP; mmHg)	At the time of presentation (on day 1)	Echocardiographic determination of right heart parameters under rest and during exercise
Echocardiographic right heart parameters - Tricuspid annular plane systolic excursion (TAPSE; mm)	At the time of presentation (on day 1)	Echocardiographic determination of right heart parameters under rest and during exercise
Measurement of gas exchange under different inhaled oxygen concentrations	At the time of presentation (on day 1)	Non-invasive estimation of ventilation/perfusion (V/Q) mismatch
Echocardiographic right heart parameters - right ventricular (RV) end-ventricular volume (EDV; ml)	At the time of presentation (on day 1)	Echocardiographic determination of right heart parameters under rest and during exercise
Spiroergometric capacity- maximal oxygen uptake (VO2max; ml/min/kg)	At the time of presentation (on day 1)	Determination of exercise capacity by cardiopulmonary exercise testing (CPET)
Echocardiographic right heart - right volume (RV) end-systolic volume (ESV; ml)	At the time of presentation (on day 1)	Echocardiographic determination of right heart parameters under rest and during exercise
Echocardiographic right heart - right ventricular longitudinal global strain (%)	At the time of presentation (on day 1)	Echocardiographic determination of right heart parameters under rest and during exercise
Dyspnoea Index	At the time of presentation (on day 1)	Determination of dyspnea and functional capacity a questionaire measure of shortness of breath for determining exertion levels
Invasive hemodynamics - pulmonary vascular resistance (PVR; WU)	At the time of presentation (on day 1)	Invasive measurement of pulmonary hemodynamics by right heart catheterization (RHC subgroup)
Invasive hemodynamics - cardiac Index (CI; l/min/m2)	At the time of presentation (on day 1)	Invasive measurement of pulmonary hemodynamics by right heart catheterization (RHC subgroup)

Secondary Outcome Measures

Name	Time	Method
Airway Impedance	At the time of presentation (on day 1)	Determination of airway impedance by oscillometry
Static and dynamic lung function parameters - forced expiratory volume in 1 s (FEV1; L)	At the time of presentation (on day 1)	Determination of lung function by body plethysmography at rest
Shunt measurement	At the time of presentation (on day 1)	Shunt measurement by contrast-enhanced echocardiography (optional)
Left heart parameters - (E/e' ratio)	At the time of presentation (on day 1)	Determination of left heart parameters during rest and exercise
Left heart parameters - left ventricular ejection fraction (%)	At the time of presentation (on day 1)	Determination of left heart parameters during rest and exercise
Pulmonary vascular function	At the time of presentation (on day 1)	Increase of echocardiographically estimated systolic pulmonary arterial pressure during inhalation of hypoxic gas
Peripheral blood mononuclear cells	At the time of presentation (on day 1)	Determination of characteristics of peripheral immune cells by fluorescence activated cell sorter (FACS) and functional assays
Static and dynamic lung function parameters - vital capacity (VC; L)	At the time of presentation (on day 1)	Determination of lung function by body plethysmography at rest
Static and dynamic lung function parameters - diffusion capacity (DLCO; %)	At the time of presentation (on day 1)	Determination of lung function by body plethysmography at rest
Static and dynamic lung function parameters - diffusion coefficient (DLCO/VA; %)	At the time of presentation (on day 1)	Determination of lung function by body plethysmography at rest
Ventilation/Perfusion mismatch	At the time of presentation (on day 1)	Determination of V/Q mismatch using the gold standard multiple inert gas elimination technique (MIGET) (only in RHC subgroup)

Trial Locations

Locations (1)

Natascha Sommer; 🇩🇪 Giessen, Germany