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.
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).
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).
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
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.
Universidade de Passo Fundo
Passo Fundo, 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
Univesidade de Ciências da Saúde de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Nossa Senhora da Conceição
Porto Alegre, Rio Grande Do Sul, Brazil
Danilo C Berton, Dr, Principal Investigator
Universidade Federal do Rio Grande do Sul/Hospital de Clínicas de Porto Alegre