Lung Function, Exercise Capacity and Health-Related Quality of Life After Severe COVID-19

Short and Long Term Assessment of Lung Function, Exercise Capacity and Health-Related Quality of Life in Survivors of Severe COVID-19

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Diagnostic test: Lung Function tests; Diagnostic test: Exercise capacity; Diagnostic test: Exercise physiology; Diagnostic test: Health-related quality of life; Diagnostic test: Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening

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).

• Study Type: Observational
• Enrollment (Actual): 144

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99052-900
      • Universidade de Passo Fundo
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-000
      • Hospital Moinhos de Vento
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
      • Hospital de Clínicas de Porto Alegre/Universidade Federal do Rio Grande do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
      • Univesidade de Ciências da Saúde de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Subjects that survived severe COVID-19

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe Pneumonia; 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.	Diagnostic test: Lung Function tests; Spirometry before and after bronchodilator, lung volumes by body plethysmography, lung diffusion capacity of carbon monoxide (DLCO), respiratory system resistance by impulse oscillometry (IOS); Diagnostic test: Exercise capacity; 6-minute walk test (6MWT distance); Diagnostic test: Exercise physiology; Cardiopulmonary exercise test (CPET); Diagnostic test: Health-related quality of life; Short-Form Health Survey Questionnaire (SF-36); Diagnostic test: Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening; Adapted translation American Thoracic Society respiratory symptoms questionnaire;; Beck Anxiety Inventory (BAI) and Beck's depression Inventory (BDI);; Questionnaire for screening for post-traumatic stress symptoms (PTSD).
Acute respiratory distress syndrome (ARDS); 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.	Diagnostic test: Lung Function tests; Spirometry before and after bronchodilator, lung volumes by body plethysmography, lung diffusion capacity of carbon monoxide (DLCO), respiratory system resistance by impulse oscillometry (IOS); Diagnostic test: Exercise capacity; 6-minute walk test (6MWT distance); Diagnostic test: Exercise physiology; Cardiopulmonary exercise test (CPET); Diagnostic test: Health-related quality of life; Short-Form Health Survey Questionnaire (SF-36); Diagnostic test: Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening; Adapted translation American Thoracic Society respiratory symptoms questionnaire;; Beck Anxiety Inventory (BAI) and Beck's depression Inventory (BDI);; Questionnaire for screening for post-traumatic stress symptoms (PTSD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in the first second/forced vital capacity	ratio obtained from measured values during spirometry	6 months
Total lung capacity	obtained from plethysmography (% of predicted)	6 months
Lung diffusion capacity for carbon monoxide	obtained from single-breathe maneuver (% of predicted)	6 months
6-minute walk test distance	distance walked during the test (m)	6 months
Short-form 36 questionnaire (SF-36)	scores range between 0 and 100 with higher scores indicating a better HRQoL	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in the first second/forced vital capacity	ratio obtained from measured values during spirometry	12 and 24 months
Forced vital capacity	% of predicted	6, 12 and 24 months
Residual volume/total lung capacity	ratio obtained from measured values during plethysmography	6, 12 and 24 months
Inspiratory capacity/total lung capacity	ratio obtained from measured values during plethysmography	6, 12 and 24 months
Airway resistance (Raw)	obtained from body plethysmography	6, 12 and 24 months
Lung diffusion capacity for carbon monoxide	obtained from single-breathe maneuver (% of predicted)	12 and 24 months
Resistance at 20Hz and 5Hz (R5-R20)	obtained from Impulse oscillometry	6, 12 and 24 months
Reactance at 5Hz (X5)	obtained from Impulse oscillometry	6, 12 and 24 months
Resonant frequency (Fres)	obtained from Impulse oscillometry	6, 12 and 24 months
Reactance area (AХ)	obtained from Impulse oscillometry	6, 12 and 24 months
6-minute walk test distance	distance walked during the test (m)	12 and 24 months
Pulse oximetry (SpO2) at rest	before 6-minute walk test	6, 12 and 24 months
Pulse oximetry (SpO2) during exercise	at the end of 6-minute walk test	6, 12 and 24 months
Respiratory symptoms adapted from American Thoracic Society Questionnaire	descriptive/qualitative questionnaire	6, 12 and 24 months
Short-form 36 questionnaire (SF-36)	scores range between 0 and 100 with higher scores indicating a better HRQoL	12 and 24 months
Oxygen uptake at peak exercise	from incremental Cardiopulmonary exercise test (% of predicted)	6, 12 and 24 months
Minute-ventilation/carbon dioxide output during exercise	from incremental Cardiopulmonary exercise test (L/L)	6, 12 and 24 months
Dyspnea during exercise	from incremental Cardiopulmonary exercise test (measured with 10-point categorical Borg scale)	6, 12 and 24 months
Inspiratory capacity during exercise	from incremental Cardiopulmonary exercise test (L and % of predicted)	6, 12 and 24 months
Beck Anxiety Inventory (BAI)	total score ranges from 0 to 63; higher score indicating higher anxiety	6, 12 and 24 months
Beck Depression Inventory (BDI)	total scores ranges from 0 to 63; higher score is worse	6, 12 and 24 months
Post-traumatic stress symptoms questionnaire	17-item, 5 likert-scale each item; higher score indicating more symptoms	6, 12 and 24 months

Collaborators and Investigators

• Sponsor: Federal University of Rio Grande do Sul
• Collaborators: Hospital de Clinicas de Porto Alegre; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Federal University of Health Science of Porto Alegre; Hospital Moinhos de Vento; Universidade de Passo Fundo; Hospital Nossa Senhora da Conceicao
• Investigators: Principal Investigator: Danilo C Berton, Dr, Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Quality of Life; Pneumonia; Severe Acute Respiratory Syndrome Coronavirus 2; Respiratory Function Tests; Respiratory Distress Syndrome, Adult
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 2020-0169

Drug and device information, study documents

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