Epidemiologic, Clinical and Molecular Characteristics of Patients With Acute Respiratory Failure Affected by 2019-NCOV.

The study is a cohort study with retrospective-prospective data collection. All the
clinical data collected in the study are usually monitored in the clinical practice and
no additional clinical exams will be required for the sole purpose of the study.

Patients will be asked consent for the research use of blood and bronchial
lavage/residual samples from nasopharyngeal swabs to perform cellular and molecular
analyses aimed at better understanding the disease pathogenesis and the individual
differences in susceptibility to the disease. These experiments will have no direct
impact on the clinical management of patients. It is impossible to detail now all the
experiments that will be performed on stored samples. It is possible to anticipate that
samples could be used to analyze the immune response by studying immune cells and soluble
mediators of the immune response. Moreover, samples will be used to extract nucleic acids
to analyze gene expression profiles and DNA variations possibly related with disease
susceptibility. Part of the genetic studies could be conducted in other laboratories
abroad (i.e. the Institute of Clinical Molecular Biology of the
Christian-Albrechts-University of Kiel and the Institute of Clinical Medicine of the
University of Oslo) as part of scientific collaborations. In particular, the
investigators plan to study the expression levels of molecules known to mediated viral
infection, like the Angiotensin converting enzyme 2 (ACE2) and the Transmembrane
protease, serine 2 enzyme (TMPRSS2). Genetic variants in these genes, and more in general
in other genes in the genome, could be related to susceptibility to the viral infection
and/or to the severity of the clinical course of the disease. Therefore, the
investigators plan to compare the frequency of genetic variants potentially related with
COVID-19 susceptibility/severity in different subgroups of patients, ranging from
individuals positive for the virus but asymptomatic to individuals affected by COVID-19
with ARDS requiring admission to ICU. The extension of the analyses that will be
performed can't be anticipated as it depends also on the amount of funding that will be
available to the study; potentially the entire genome could be analyzed.

Original sepsis and ARDS biomarkers developed at ICH (e.g. PTX3, sIL-1R2, MSF) will be
used to address their prognostic potential in COVID-19 patients. PBMC will be analyzed by
FACS to investigate the immunophenotype and correlate it to the clinical outcome.
Original markers of leukocyte functional activation developed at ICH will be included in
the analysis (e.g. IL-1R8, IL-1R2). The residual BAL and rhinopharyngeal swab will be
used for microbiota analysis, metabolomics and cytokine measurement. Plasma and
saliva/sputum will be used also to test anti-SARS-Cov-2 antibodies (IgM, IgG and IgA) and
for microbiota analysis.

In order to better describe the populations of COVID-19 patients treated at our hospital,
it is necessary to collect disease outcome data over a short, medium and long-term
follow-up process. The investigators aim to understand how disease and intensive
treatments affect the lives of recovering patients. In particular, the investigators want
to explore the health-related quality of life, the impact of the disease on a
psychological level, the residual cardio-respiratory functional capacity and muscle
strength. All the tests chosen are common use tests in the follow-up of critically ill
patients in particular with acute respiratory distress syndrome.

The health-related quality of the life will be measured with the validated international
questionnaire EQ-5D-5L, in its Italian validated form. The questionnaire is attached, and
has been authorized for free non-commercial use by the EuroQuol consortium.

As a screening tool to evaluate the presence of psychological symptoms, such as anxiety
and depression, the Hospital Anxiety and Depression Scale (HADS) questionnaire will be
administered in its Italian version.

The cardio-respiratory functional capacity will be measured with the Six-Minutes Walk
Test, following the international guidelines published by the American Thoracic Society.

The single breath count tets will be performed, as well. It consists in the ability to
count from zero to twenty after a single maximum inspiration.

Finally, dynamic tests such as the Timed Up-and-Go (TUG) test and the Short physical
performance battery (SPPB) test will be performed to evaluate muscle strength, in
particular of the lower limbs, the ability to balance while walking and the general
mobility of patients. Both the aforementioned tests re internationally validated and are
commonly used in the evaluation of the functional reserve of patients in the geriatric
and rehabilitation setting. All this tests can be administered to patients during their
hospital stay or after their discharge at scheduled appointments.