Lung Function, Exercise Capacity and Health-Related Quality of Life After Severe COVID-19
- Conditions
- COVID-19SARS-CoV-2 Infection
- Interventions
- Diagnostic Test: Lung Function testsDiagnostic Test: Exercise capacityDiagnostic Test: Exercise physiologyDiagnostic Test: Health-related quality of lifeDiagnostic Test: Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening
- Registration Number
- NCT04410107
- Lead Sponsor
- Federal University of Rio Grande do Sul
- Brief Summary
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus (SARS-CoV-2) that can progress to severe disease requiring hospitalization and oxygen support in around14% of the cases and 5% require admission in intensive care unit. The medium and long-term impact in survivors of severe COVID-19 on lung function, exercise capacity and health-related quality of life remains to be determined.
- Detailed Description
Background: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) that was first recognized in Wuhan, China, in December 2019. Currently, this infection reached pandemic levels causing serious diseases in 14% of cases and the potential to progress to acute respiratory distress syndrome (ARDS) with the need for invasive ventilatory support and prolonged hospitalization in intensive care units (ICU). The overall lethality is 2% and the lethality of cases admitted to the ICU varies from 26 to 50%. The medium and long-term impact in survivors of severe COVID-19 on lung function, exercise capacity and health related quality of life (HRQoL) remains to be determined.
Aims: To evaluate the early (Visit1: 2-6 months after acute disease) and late (Visit 2: 9-15 months and Visit 3: 18-24 months) effects of severe acute respiratory syndrome on lung function, exercise capacity, respiratory symptoms and HRQoL in patients with confirmed diagnosis of SARS-CoV-2 infection.
Material and methods: Prospective cohort of subjects with laboratory confirmed severe COVID-19 (respiratory rate\> 30 breaths/ min; severe respiratory distress; oxyhemoglobin saturation in room air ≤93% or pulmonary involvement\> 50% in chest images). Participants will perform spirometry before and after bronchodilator, lung volumes by body plethysmography, lung diffusion capacity of carbon monoxide, respiratory system resistance by impulse oscillometry and 6-minute walk test (6MWT) after 2-6 months (Visit 1) , 9-15 months (Visit 2), and 18-24 months (Visit 3) of severe COVID-19. When abnormalities in these pulmonary function tests and/or 6MWT were detected, a cardiopulmonary exercise test will be performed. Clinical, laboratory and chest image data during the severe COVID-19 hospitalization will be obtained from medical records.
The minimum sample size was estimated as 134 participants to assess at least 5 independent factors to predict lung function, HRQoL and exercise capacity at the early assessment. Notwithstanding, the investigators plan to invite to participate all survivors of severe COVID-19 admitted in hospitals of the state of Rio Grande do Sul (Brazil).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 144
- Previous laboratory confirmation of SARS-Cov-2 infection defined as a positive result of reverse polymerase-transcriptase chain reaction test in real-time of a sample taken by nasal and/or pharyngeal swab; and
- Severe pneumonia defined by the presence of fever or suspected lower respiratory infection, plus one of the following criteria: respiratory rate> 30 movements/min; severe respiratory distress; SpO2≤93% in room air; or pulmonary infiltrates>50% on chest imaging within 24-48hrs of acute symptoms onset; and/or
- Acute respiratory distress syndrome (ARDS) defined according to COVID-19 operational management guide of World Health Organization and classified as mild (200 mmHg <PaO2 / FiO2 ≤ 300 mmHg), moderate (100 mmHg <PaO2 / FiO2 ≤ 200 mmHg) or severe (PaO2 / FiO2 ≤ 100 mmHg). When the PaO2 is not available, SpO2 / FiO2 ≤ 315 suggests ARDS.
- Lack of clinical stability for 2 months before inclusion (including those who remain hospitalized);
- Active respiratory tract infection (of any cause); or
- Any clinical condition that prevents the performance of the study procedures.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Acute respiratory distress syndrome (ARDS) Exercise capacity * Onset: acute, i.e. within 1 week of known clinical insult or new or worsening respiratory symptoms; and * Chest imaging (e.g. X-ray or CT scan): bilateral opacities, not fully explained by effusions, lobar/lung collapse or nodules; and * Origin of pulmonary edema: respiratory failure not fully explained by cardiac failure or fluid overload; and * Degree of hypoxemia: arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O. Acute respiratory distress syndrome (ARDS) Exercise physiology * Onset: acute, i.e. within 1 week of known clinical insult or new or worsening respiratory symptoms; and * Chest imaging (e.g. X-ray or CT scan): bilateral opacities, not fully explained by effusions, lobar/lung collapse or nodules; and * Origin of pulmonary edema: respiratory failure not fully explained by cardiac failure or fluid overload; and * Degree of hypoxemia: arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O. Acute respiratory distress syndrome (ARDS) Health-related quality of life * Onset: acute, i.e. within 1 week of known clinical insult or new or worsening respiratory symptoms; and * Chest imaging (e.g. X-ray or CT scan): bilateral opacities, not fully explained by effusions, lobar/lung collapse or nodules; and * Origin of pulmonary edema: respiratory failure not fully explained by cardiac failure or fluid overload; and * Degree of hypoxemia: arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O. Severe Pneumonia Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening Presence of fever or suspected lower respiratory infection, plus one of the following criteria: 1) respiratory rate\> 30 movements / min; 2) severe respiratory distress 3) Pulse oximetry (SpO2) ≤93% in room air; and/or 3) Pulmonary infiltrates\> 50% on chest imaging within 24-48hrs of symptom onset. Severe Pneumonia Exercise capacity Presence of fever or suspected lower respiratory infection, plus one of the following criteria: 1) respiratory rate\> 30 movements / min; 2) severe respiratory distress 3) Pulse oximetry (SpO2) ≤93% in room air; and/or 3) Pulmonary infiltrates\> 50% on chest imaging within 24-48hrs of symptom onset. Severe Pneumonia Exercise physiology Presence of fever or suspected lower respiratory infection, plus one of the following criteria: 1) respiratory rate\> 30 movements / min; 2) severe respiratory distress 3) Pulse oximetry (SpO2) ≤93% in room air; and/or 3) Pulmonary infiltrates\> 50% on chest imaging within 24-48hrs of symptom onset. Acute respiratory distress syndrome (ARDS) Lung Function tests * Onset: acute, i.e. within 1 week of known clinical insult or new or worsening respiratory symptoms; and * Chest imaging (e.g. X-ray or CT scan): bilateral opacities, not fully explained by effusions, lobar/lung collapse or nodules; and * Origin of pulmonary edema: respiratory failure not fully explained by cardiac failure or fluid overload; and * Degree of hypoxemia: arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O. Severe Pneumonia Lung Function tests Presence of fever or suspected lower respiratory infection, plus one of the following criteria: 1) respiratory rate\> 30 movements / min; 2) severe respiratory distress 3) Pulse oximetry (SpO2) ≤93% in room air; and/or 3) Pulmonary infiltrates\> 50% on chest imaging within 24-48hrs of symptom onset. Severe Pneumonia Health-related quality of life Presence of fever or suspected lower respiratory infection, plus one of the following criteria: 1) respiratory rate\> 30 movements / min; 2) severe respiratory distress 3) Pulse oximetry (SpO2) ≤93% in room air; and/or 3) Pulmonary infiltrates\> 50% on chest imaging within 24-48hrs of symptom onset. Acute respiratory distress syndrome (ARDS) Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening * Onset: acute, i.e. within 1 week of known clinical insult or new or worsening respiratory symptoms; and * Chest imaging (e.g. X-ray or CT scan): bilateral opacities, not fully explained by effusions, lobar/lung collapse or nodules; and * Origin of pulmonary edema: respiratory failure not fully explained by cardiac failure or fluid overload; and * Degree of hypoxemia: arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ≤ 300 mm Hg with positive end-expiratory pressure ≥ 5 cm H2O.
- Primary Outcome Measures
Name Time Method Total lung capacity 6 months obtained from plethysmography (% of predicted)
Lung diffusion capacity for carbon monoxide 6 months obtained from single-breathe maneuver (% of predicted)
Forced expiratory volume in the first second/forced vital capacity 6 months ratio obtained from measured values during spirometry
6-minute walk test distance 6 months distance walked during the test (m)
Short-form 36 questionnaire (SF-36) 6 months scores range between 0 and 100 with higher scores indicating a better HRQoL
- Secondary Outcome Measures
Name Time Method Short-form 36 questionnaire (SF-36) 12 and 24 months scores range between 0 and 100 with higher scores indicating a better HRQoL
Minute-ventilation/carbon dioxide output during exercise 6, 12 and 24 months from incremental Cardiopulmonary exercise test (L/L)
Reactance at 5Hz (X5) 6, 12 and 24 months obtained from Impulse oscillometry
Resonant frequency (Fres) 6, 12 and 24 months obtained from Impulse oscillometry
Pulse oximetry (SpO2) at rest 6, 12 and 24 months before 6-minute walk test
Inspiratory capacity/total lung capacity 6, 12 and 24 months ratio obtained from measured values during plethysmography
Lung diffusion capacity for carbon monoxide 12 and 24 months obtained from single-breathe maneuver (% of predicted)
Pulse oximetry (SpO2) during exercise 6, 12 and 24 months at the end of 6-minute walk test
Forced vital capacity 6, 12 and 24 months % of predicted
Residual volume/total lung capacity 6, 12 and 24 months ratio obtained from measured values during plethysmography
6-minute walk test distance 12 and 24 months distance walked during the test (m)
Beck Anxiety Inventory (BAI) 6, 12 and 24 months total score ranges from 0 to 63; higher score indicating higher anxiety
Beck Depression Inventory (BDI) 6, 12 and 24 months total scores ranges from 0 to 63; higher score is worse
Forced expiratory volume in the first second/forced vital capacity 12 and 24 months ratio obtained from measured values during spirometry
Airway resistance (Raw) 6, 12 and 24 months obtained from body plethysmography
Post-traumatic stress symptoms questionnaire 6, 12 and 24 months 17-item, 5 likert-scale each item; higher score indicating more symptoms
Resistance at 20Hz and 5Hz (R5-R20) 6, 12 and 24 months obtained from Impulse oscillometry
Reactance area (AХ) 6, 12 and 24 months obtained from Impulse oscillometry
Respiratory symptoms adapted from American Thoracic Society Questionnaire 6, 12 and 24 months descriptive/qualitative questionnaire
Inspiratory capacity during exercise 6, 12 and 24 months from incremental Cardiopulmonary exercise test (L and % of predicted)
Oxygen uptake at peak exercise 6, 12 and 24 months from incremental Cardiopulmonary exercise test (% of predicted)
Dyspnea during exercise 6, 12 and 24 months from incremental Cardiopulmonary exercise test (measured with 10-point categorical Borg scale)
Trial Locations
- Locations (5)
Hospital Nossa Senhora da Conceição
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Clínicas de Porto Alegre/Universidade Federal do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Universidade de Passo Fundo
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Univesidade de Ciências da Saúde de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil