Prospective Study of Persistent Dyspnea in Recovered COVID-19 Patients (DISCOVID19)

We conducted a national, single center (Hospital Clínico Universitario de Valladolid, Spain, Valladolid), prospective study of patients with prior hospitalization because of COVID-19 who were admitted between March 1st, 2020, and May 15th, 2020. All eligible patients underwent at least at first-time follow-up from the index event. Exclusion criteria were age < 18 years old, pregnant women, terminally ill patients, active SARS-CoV-2 infections, inability to exercise and previous known severe pulmonary or heart disease. Patients underwent a clinical assessment for symptom burden, questionnaire for quality of life (Kansas City Cardiomyopathy Questionnaire and SF-36), venous blood sampling, 6-minute walking test (6-MWT), tests of lung function (spirometry and diffusing capacity of the lungs for carbon monoxide) and treadmill cardio-pulmonary exercise testing (CPET). 48-hours before the test of lung function and the CPET, all patients yielded a negative result in the reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2. For definitive analysis patients were assigned to the control group if they did not refer dyspnea at the time of the follow-up, a small asymptomatic out-patient control group without prior hospitalization was also included.

Study Overview

• Status: Completed
• Conditions: Covid19; Dyspnea
• Intervention / Treatment: Diagnostic test: Cardiopulmonary exercise test

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Spain
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with prior hospitalization because of COVID-19 who were admitted between March and May. All eligible patient underwent at least at first-time follow-up from the index event. Exclusion criteria were age < 18 years old, pregnant women, terminally ill patients, active SARS-CoV-2 infections, inability to exercise and previous known severe pulmonary or heart disease.

Description

Inclusion Criteria:

• Signed Informed Consent
• Previous COVID-19 hospitalization with successful discharged
• Availability of at least one follow up per clinical protocol

Exclusion Criteria:

• pregnant women
• terminally ill patients
• active SARS-CoV-2 infections
• inability to exercise
• previous known severe pulmonary or heart disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dyspnea; Patients with prior hospitalization because of COVID-19, with succesful hospital discharge, who underwent at least a first-time follow-up from the index event, and present persistent dyspnea.	Diagnostic test: Cardiopulmonary exercise test; Only diagnostic tests; Other Names: blood sampling; echocardiography; walking test; pulmonary lung test
Control; Patients with prior hospitalization because of COVID-19, with succesful hospital discharge, who underwent at least a first-time follow-up from the index event, fully recovered, without persistent dyspnea.	Diagnostic test: Cardiopulmonary exercise test; Only diagnostic tests; Other Names: blood sampling; echocardiography; walking test; pulmonary lung test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aerobic capacity	Measured as peak oxygen uptake	6 months
Total Lung Capacity (TLC)	Pulmonary function test	6 months
Force Expiratory Volume in 1 second (FEV1)	Pulmonary function test	6 months
Difussing Lung Capacity of CO (DLCO)	Pulmonary function test	6 months
Forced Vital Capacity (FVC)	Pulmonary function test	6 months
Left Ventricular (LV) Function	Left Ventricular (LV) Function (Ecocardiagraphy-measured Cardiac Function)	6 months
Right Ventricular (RV) Function	Right Ventricular (RV) Function (Ecocardiagraphy-measured Cardiac Function)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short Form 36 Health Survey (SF-36)	Quality of Life test	6 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Quality of Life test	6 Months
6 Minute Walk Test	Walking capacity	6 months
N-terminal pro hormone B-type natriuretic peptide (NT-proBNP)	Inflammatory and Cardiac Marker	6 months
Troponin-T	Inflammatory and Cardiac Marker	6 months
Ferritin	Inflammatory and Cardiac Marker	6 months
D-Dimer	Inflammatory and Cardiac Marker	6 months
interleukine-6	Inflammatory and Cardiac Marker	6 months
C reactive protein (CRP)	Inflammatory and Cardiac Marker	6 months

Collaborators and Investigators

• Sponsor: Hospital Clínico Universitario de Valladolid

Publications and helpful links

General Publications

• Pinney SP, Giustino G, Halperin JL, Mechanick JI, Neibart E, Olin JW, Rosenson RS, Fuster V. Coronavirus Historical Perspective, Disease Mechanisms, and Clinical Outcomes: JACC Focus Seminar. J Am Coll Cardiol. 2020 Oct 27;76(17):1999-2010. doi: 10.1016/j.jacc.2020.08.058.
• Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, Eyre L, Breen A, O'Connor R, Jones A, Sivan M. Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis. J Rehabil Med. 2020 May 31;52(5):jrm00063. doi: 10.2340/16501977-2694.
• Aparisi A, Ybarra-Falcon C, Garcia-Gomez M, Tobar J, Iglesias-Echeverria C, Jaurrieta-Largo S, Ladron R, Uribarri A, Catala P, Hinojosa W, Marcos-Mangas M, Fernandez-Prieto L, Sedano-Gutierrez R, Cusacovich I, Andaluz-Ojeda D, de Vega-Sanchez B, Recio-Platero A, Sanz-Patino E, Calvo D, Baladron C, Carrasco-Moraleja M, Disdier-Vicente C, Amat-Santos IJ, San Roman JA. Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation. J Clin Med. 2021 Jun 11;10(12):2591. doi: 10.3390/jcm10122591.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 29, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Covid19; Dyspnea; Cardiopulmonary exercise test
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Signs and Symptoms, Respiratory; COVID-19; Dyspnea
• Other Study ID Numbers: CASVE PI-20-1894

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No