Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (COVID-19)

Covid-19 Clinical Trial

— CovILD  

Official title:

Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04416100
• Other study ID #: 20200429-2255
• Status: Recruiting
• Start date: April 29, 2020
• Est. completion date: April 28, 2022

Study information

• Verified date: May 2020
• Source: Medical University Innsbruck
• Contact: Judith Löffler-Ragg, Prof. Dr.
• Phone: +43-512-504-81413
• Email: judith.loeffler[@]i-med.ac.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses a global economic, social, political and medical challenge. The virus originated in December 2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries, including Austria, are severely affected.The most common computed tomographic changes in acute lung injury include bilateral and subpleural milk glass opacity, consolidation in lower lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of symptoms) a so-called "crazy paving" may occur. The most prominent radiological changes occur around day 10, followed by gradual resolution, which begins two weeks after the onset of symptoms.

Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical course in severe cases and overlapping CT patterns in the acute setting, persistent radiological and pulmonary functional changes in survivors are conceivable. It is also conceivable that a proportion of survivors will develop progressive ILD, either due to viral or ventilator-induced alveolar damage, or both.

Here, the investigators intend to investigate COVID-19 survivors through clinical examinations, functional lung examinations, HR-CT scans, and by determining the "immunofibrotic" pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after discharge.

Description:

COVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, currently poses a global economic, social, political and medical challenge. The virus originated in December 2019 in Wuhan, China, and has spread rapidly around the world. Currently, European countries, including Austria, are severely affected. In January 2020, the World Health Organisation declared a "Public Health Event of International Concern" and since 11 March 2020 COVID-19 has been classified as a pandemic. Overall mortality rates vary widely, ranging from 0.5 to 7%. These highly depend on the stringency of the tests in a particular region and the age of the patients with higher mortality rates in older people. The majority of patients show only mild symptoms with fever and/or cough, and it is even believed that there is a significant proportion of untested asymptomatic carriers that can transmit the virus to other people. 26 to 33% of in-patients have been admitted to intensive care due to a severe lung disease. Of these, 2.5 to 10% required invasive mechanical ventilation and 15 to 22% of these patients died in hospital, indicating the potential risk to public health. As a result, the current global death toll from COVID-19 already exceeds 37,000 people on 31 March 2020.

In the SARS-CoV-1 outbreak of 2003, clinical course was characterized by fever, myalgia and other systemic symptoms, which generally improved after a few days, followed by a second phase with recurrence of fever, oxygen saturation and imaging progression of pneumonia, similar to that experienced by severely affected patients in the current pandemic. Importantly, a significant number of patients infected with SARS-CoV-1 suffered acute respiratory failure (ARDS) requiring invasive ventilatory support. The pulmonary pathology of fatal SARS cases was dominated by diffuse alveolar damage (DAD), epithelial cell proliferation, an increase in macrophages in the lung and extensive consolidation, but features of bronchiolitis obliterans and organizing pneumonia were also noted. In addition, survivors of severe SARS-CoV-1 infection showed significant functional and radiological changes in the lungs even 6 months after infection.

In the current SARS-CoV-2 pandemic, the most common computed tomographic changes in acute lung injury include bilateral and subpleural milk glass opacity, consolidation in lower lobes, or both. In the intermediate phase of the infection (4-14 days after the onset of symptoms) a so-called "crazy paving" may occur. The most prominent radiological changes occur around day 10, followed by gradual resolution, which begins two weeks after the onset of symptoms.

Given the phylogenetic relationship between SARS-CoV-1 and SARS-CoV-2, the similar clinical course in severe cases and overlapping CT patterns in the acute setting, persistent radiological and pulmonary functional changes in survivors are conceivable. It is also conceivable that a proportion of survivors will develop progressive ILD, either due to viral or ventilator-induced alveolar damage, or both.

Here, the investigators intend to investigate COVID-19 survivors through clinical examinations, functional lung examinations, HR-CT scans, and by determining the "immunofibrotic" pattern in peripheral mononuclear cells (PBMCs) 1, 3, and 6 months after discharge.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: April 28, 2022
• Est. primary completion date: April 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female and male patients = 18 years.

• Confirmed infection with SARS-CoV-2 according to the definition of the Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection

• Signed and dated declaration of consent by the patient according to ICH-GCP Guidelines.

Exclusion Criteria:

• Female and male patients < 18 years

• Pregnancy

• Dementia

• Declaration of consent by the patient according to ICH-GCP Guidelines not signed

• Incapacitated patients

Related Conditions & MeSH terms

• Covid-19
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

Diagnostic Test:
• Pulmonary function tests
Spirometry or plethysmography, measurement of diffusion capacity
• Imaging
HRCT and echocardiography as scheduled within routine clinical examinations

Biological:
• Blood sampling
Standard laboratory test as part of routine clinical examination and collection of peripheral blood for immunofibrotic phenotyping

Locations

Country	Name	City	State
Austria	Medical University of Innsbruck	Innsbruck

Sponsors (2)

Lead Sponsor	Collaborator
Medical University Innsbruck	Boehringer Ingelheim

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 1 month	Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 1 month after discharge or diagnosis of COVID-19 disease by the use of HR-CT.	1 month
Primary	Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 3 months	Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 3 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT	3 months
Primary	Pattern of pulmonary abnormalities in SARS-CoV2 infected patients after 6 months	Define the frequency of ILD and pulmonary vascular disease in SARS-CoV-2 infected patients with a severe/prolonged Course (inhospital stay, either on the normal ward or ICU), with and without oxygen supplementation, non-invasive or invasive ventilation) at 6 months after discharge or diagnosis of COVID-19 disease by the use of HR-CT	6 months