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

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.