Lung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19) (SequelaeCov)

SequelaeCov: a Prospective Study on Lung Damage Caused by SARS-CoV-2 Pneumonia

Pneumonia is a recurrent element of COVID-19 infection, it is often associated with development of respiratory failure and patients frequently need various degrees of oxygen therapy up to non invasive ventilation (NIV-CPAP) and invasive mechanical ventilation (IMV).

Main purpose of this study is to evaluate with non invasive clinical instruments (pletysmography, Diffusion lung capacity for carbon monoxide -DLCO-, six minute walking test and dyspnea scores) and radiological tools (chest X-ray and chest CT scan) the development of medium-to-long term pulmonary sequelae caused by SARS-CoV-2 pneumonia.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Viral; Emphysema; COVID; Interstitial Lung Disease; Bronchiectasis Adult; Barotrauma

Detailed Description

SARS-CoV-2 related disease started in December 2019 in the Chinese city of Wuhan, rapidly spread and became an international health emergency.

Pneumonia is a frequent element of COVID-19, its pathogenic mechanisms are not entirely known and some patients develop various degrees of respiratory failure and need oxygen therapy up to NIV-CPAP) and IMV.

Some pathology studies in COVID-19 pneumonia show ARDS-like lesions associated to inflammatory reaction. It is known that pulmonary inflammatory damage can lead to fibrotic sequelae or to the development of pulmonary emphysema.

The main target of the study is to use non invasive methods (pletysmography, DLCO assessment, six minute walking test and dyspnea scores) and radiological tools (chest X-ray and chest CT scan) to identify pulmonary sequelae in patients hospitalised because of respiratory failure in COVID-19 pneumonia.

Study design: multicentre observational cohort study. Patients will be divided in three arms according to maximum ventilatory/oxygen support received during hospital stay:

1. patients who received only oxygen therapy
2. patients who received non invasive ventilation (NIV-CPAP)
3. patients who received invasive mechanical ventilation (IMV)

All patients undergo a clinical evaluation at 6 months from hospital discharge (T1) and a second clinical evaluation at 12 months from hospital discharge (T2).

During (T1) patients undergo spirometry with pletysmography and DLCO assessment, six minute walking test, standard chest X-ray, arterial blood gas analysis if SaO2 < 93% in room air, dyspnea score and presence and extension of lung sounds at pulmonary auscultation.

During (T2) patients will undergo spirometry with pletysmography and DLCO assessment, six minute walking test, High Resolution CT scan (HRTC) of the thorax, arterial blood gas analysis if SaO2 < 93% in room air, dyspnea score and presence and extension of lung sounds at pulmonary auscultation).

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Italy
  • MB
    • Monza, MB, Italy, 20900
      • San Gerardo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with respiratory failure (P/F < 300) due to SARS-CoV-2 pneumonia

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 80 years
• Able to sign informed consent to participate in the study
• Real time PCR diagnosis od SARS-CoV-2 infection
• Hospital admission due to clinical/instrumental diagnosis of interstitial pneumonia
• Presence of acute respiratory failure (PaO2/FiO2 <300 mm Hg) at the moment of hospital admission

Exclusion Criteria:

• Severe renal failure defined as glomerular filtration rate (GFR) < 30 ml/min at hospital discharge
• Cardiovascular failure NYHA class IV (patient unable to perform any activity) at hospital discharge
• Active solid or hematological malignancies at hospital discharge
• Prior diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary emphysema, pulmonary fibrosis, bronchiectasis associated or not associated to cystic fibrosis
• Pregnancy or breastfeeding
• Suspected bacterial or fungine pulmonary superinfection during hospital stay

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Oxygen therapy; Patients who were hospitalised due to COVID-19 pneumonia and received only oxygen support therapy.
Non invasive ventilation (NIV/CPAP); Patients who were hospitalised due to COVID-19 pneumonia and received non invasive ventilation (NIV/CPAP) as maximum support therapy
Invasive ventilation; Patients who were hospitalised due to COVID-19 pneumonia and received invasive mechanical ventilation (IMV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Diffusion of Lung CO (DLCO, single breath technique)	Reduction below 80% of predicted values of DLCO	T1 at 6 months from discharge
Reduction of Diffusion of Lung CO (DLCO, single breath technique)	Reduction below 80% of predicted values of DLCO	T2 at 12 months from discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in 6 minute walking test (6MWT)	reduction in maximum distance walked	T1 at 6 months from discharge
Alterations in 6 minute walking test (6MWT)	reduction in maximum distance walked	T2 at 12 months from discharge
Alterations in 6 minute walking test (6MWT)	reduction in oxygen saturation nadir	T1 at 6 months from discharge
Alterations in 6 minute walking test (6MWT)	reduction in oxygen saturation nadir	T2 at 12 months from discharge
Alterations of pletismography	reduction of Forced Vital Capacity (FVC, %)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Forced Vital Capacity (FVC, %)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Forced Vital Capacity (FVC, L)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Forced Vital Capacity (FVC, L)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Vital Capacity (VC, %)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Vital Capacity (VC, %)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Vital Capacity (VC, L)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Vital Capacity (VC, L)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Forced Expiratory Volume in the 1st second (FEV1, L)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Forced Expiratory Volume in the 1st second (FEV1, %)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Forced Expiratory Volume in the 1st second (FEV1, L)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Forced Expiratory Volume in the 1st second (FEV1, L%)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Total Lung Capacity (TLC, L)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Total Lung Capacity (TLC, %)	T1 at 6 months from discharge
Alterations of pletismography	reduction of Total Lung Capacity (TLC, L)	T2 at 12 months from discharge
Alterations of pletismography	reduction of Total Lung Capacity (TLC, %)	T2 at 12 months from discharge
Alterations of pletismography	alterations of Residual Volume (RV,%)	T1 at 6 months from discharge
Alterations of pletismography	alterations of Residual Volume (RV, L)	T1 at 6 months from discharge
Alterations of pletismography	alterations of Residual Volume (RV, L)	T2 at 12 months from discharge
Alterations of pletismography	alterations of Residual Volume (RV, %)	T2 at 12 months from discharge
Alterations of pletismography	increase of Specific Airway Resistance (sRAW) (absolute value)	T1 at 6 months from discharge
Alterations of pletismography	increase of Specific Airway Resistance (sRAW) (%)	T1 at 6 months from discharge
Alterations of pletismography	increase of Specific Airway Resistance (sRAW) (absolute value)	T2 at 12 months from discharge
Alterations of pletismography	increase of Specific Airway Resistance (sRAW) (%)	T2 at 12 months from discharge
Alterations of pletismography	alterations of Motley Index (VR/CPT)	T1 at 6 months from discharge
Alterations of pletismography	alterations of Motley Index (VR/CPT)	T2 at 12 months from discharge
Alterations of pletismography	alterations of Tiffeneau Index (IT)	T1 at 6 months from discharge
Alterations of pletismography	alterations of Tiffeneau Index (IT)	T2 at 12 months from discharge
Alterations of Arterial Blood Gas Analysis	reduction of PaO2 mmHg	T1 at 6 months from discharge
Alterations of Arterial Blood Gas Analysis	reduction of PaO2 mmHg	T2 at 12 months from discharge
Alterations of Arterial Blood Gas Analysis	alteration of PaCO2 mmHg	T1 at 6 months from discharge
Alterations of Arterial Blood Gas Analysis	alteration of PaCO2 mmHg	T2 at 12 months from discharge
Abnormal Dyspnea Score	Modified Medical Research Council - mMRC > 0 (minimum 0, maximum 4; higher score means worse outcome)	T1 at 6 months from discharge
Abnormal Dyspnea Score	Modified Medical Research Council - mMRC > 0(minimum 0, maximum 4; higher score means worse outcome)	T2 at 12 months from discharge
Presence and extension of abnormal pulmonary lung sounds at auscultation	Presence and extension of abnormal pulmonary lung sounds at auscultation	T1 at 6 months from discharge
Presence and extension of abnormal pulmonary lung sounds at auscultation	Presence and extension of abnormal pulmonary lung sounds at auscultation	T2 at 12 months from discharge
Presence and extension of radiological alterations at chest X-ray	Presence and extension of radiological alterations at chest X-ray	T1 at 6 months from discharge
Presence and extension of radiological alterations at chest CT scan	Presence and extension of radiological alterations at chest CT scan	T2 at 12 months from discharge

Collaborators and Investigators

• Sponsor: University of Milano Bicocca

Publications and helpful links

General Publications

• Faverio P, Luppi F, Rebora P, Busnelli S, Stainer A, Catalano M, Parachini L, Monzani A, Galimberti S, Bini F, Bodini BD, Betti M, De Giacomi F, Scarpazza P, Oggionni E, Scartabellati A, Bilucaglia L, Ceruti P, Modina D, Harari S, Caminati A, Valsecchi MG, Bellani G, Foti G, Pesci A. Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study. Respiration. 2021;100(11):1078-1087. doi: 10.1159/000518141. Epub 2021 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2020
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): March 18, 2022

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Wounds and Injuries; Bronchial Diseases; Bronchiectasis; Lung Diseases; Pneumonia; Emphysema; Pneumonia, Viral; Lung Diseases, Interstitial; Barotrauma
• Other Study ID Numbers: SequelaeCov

Drug and device information, study documents

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