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

Study Overview
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Brief Summary
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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.

Detailed Description
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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: patients who received only oxygen therapy patients who received non invasive ventilation (NIV-CPAP) 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).

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

Conditions
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COVID, Pneumonia, Viral, Barotrauma, Interstitial Lung Disease, Bronchiectasis Adult, Emphysema

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oxygen therapy<br>Patients who were hospitalised due to COVID-19 pneumonia and received only oxygen support therapy. | |
| Non invasive ventilation (NIV/CPAP)<br>Patients who were hospitalised due to COVID-19 pneumonia and received non invasive ventilation (NIV/CPAP) as maximum support therapy | |
| Invasive ventilation<br>Patients who were hospitalised due to COVID-19 pneumonia and received invasive mechanical ventilation (IMV) | |

What is the study measuring?
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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 |