S Protein and COVID-19: a Monocentric Prospective Study

Non-pharmacological, non-interventional, prospective, monocentric study involving the use of biological materials.

There will be two cohorts:

* COVID + cohort: 50 patients with positive nasopharyngeal swab and / or BAL.
* Control Cohort: 20 patients with non-SARS-CoV-2 related pneumonia.

The study involves analyzing biological samples collected for normal clinical practice.

In particular:

* blood samples will be used for PROS and Sflt1 assay, haematological, biochemical and coagulation tests.
* Samples deriving from nasopharyngeal swab or from Broncho-Alveolar Lavage (BAL) liquid will be used for Real time PCR analysis to evaluate the viral load of SARS CoV-2.

• Hematolgy and Chemistry analysis (Procedure), also known as Peripheral Blood: Samples will be collected at Day 0, Day 5, Day 10 and Day 15
• Real Time PCR (Procedure), also known as Nasopharyngeal swab, Bronchoalveolar lavage: Samples will be collected at Day 0, Day 5, Day 10 and Day 15
• PROS assay COVID+ (Procedure), also known as Peripheral Blood: Samples will be collected at Day 0, Day 5, Day 10 and Day 15
• Sflt1 assay COVID+ (Procedure), also known as Peripheral Blood: Samples will be collected at Day 0 and Day 10
• PROS assay CONTROL (Procedure), also known as Peripheral Blood: Samples will be collected at Day 0 (+5)
• Sflt1 assay CONTROL (Procedure), also known as Peripheral Blood: Samples will be collected at Day 0 (+5)

Primary outcomes

• Plasma PROS levels compared to early stage of SARS-CoV-2 infection. [Day 0]: To demonstrate a correlation between low plasma PROS levels and the early stage of SARS-CoV-2 infection, defined as the first 10 days after onset of symptoms.
• Plasma PROS levels compared to early stage of SARS-CoV-2 infection. [Day +5]: To demonstrate a correlation between low plasma PROS levels and the early stage of SARS-CoV-2 infection, defined as the first 10 days after onset of symptoms.
• Plasma PROS levels compared to early stage of SARS-CoV-2 infection. [Day +10]: To demonstrate a correlation between low plasma PROS levels and the early stage of SARS-CoV-2 infection, defined as the first 10 days after onset of symptoms.
• Plasma PROS levels compared to early stage of SARS-CoV-2 infection. [Day +15]: To demonstrate a correlation between low plasma PROS levels and the early stage of SARS-CoV-2 infection, defined as the first 10 days after onset of symptoms.
• Plasma PROS level compared to SARS-Cov-2 viral load [Day 0]: To demonstrate a correlation between PROS and the viral load of SARS-CoV-2
• Plasma PROS level compared to SARS-Cov-2 viral load [Day+5]: To demonstrate a correlation between PROS and the viral load of SARS-CoV-2
• Plasma PROS level compared to SARS-Cov-2 viral load [Day+10]: To demonstrate a correlation between PROS and the viral load of SARS-CoV-2
• Plasma PROS level compared to SARS-Cov-2 viral load [Day+15]: To demonstrate a correlation between PROS and the viral load of SARS-CoV-2

Secondary outcomes

• Normal plasma protein S levels in patients with Pneumonia non-SARS-CoV related [Day 0, Day +5]: To confirm the non-consumption of protein S in Pneumonia other than SARS-CoV-2.
• Normal levels Plasma S potein in late stage of SARS-CoV-2 infection in COVID + patients. [Day 0, Day +5, Day +10, Day+15]: To confirm normalization of plasma S Potein levels longitudinally during the late stages of SARS-CoV-2 infection.
• Correlation between plasma levels of S protein and the severity indices of SARS-CoV-2 disease [Day 0, Day +5, Day +10, Day+15]: To detect any correlations between plasma levels of S Protein and already known parameters indicative of SARS-CoV-2 disease severity (e.g. days spent in O2 at high flows or the need for intubation; access to the Intensive Care Unit; appearance of arterial or venous thromboembolic events; coagulation activation markers; markers of inflammatory or cytokine phase; mortality).
• Plasma protein S as an index for use of immunosuppressive therapy. [Day 0, Day +5, Day +10, Day+15]: To use protein S values as an indicator for the introduction of immunosuppressive drugs in therapy in patients with COVID-19 disease.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Cohort COVID + :

* Subjects aged ≥ 18 years.
* Signing of the informed consent.
* Positivity for SARS-CoV-2 by RealTimePCR from nasopharyngeal swab or bronchial wash.

Cohort Control:

1. Subjects aged ≥ 18 years.
2. Signing of the informed consent.
3. Diagnosis of pneumonia not related to SARS-CoV-2, demonstrated by negative swab.

Exclusion Criteria:

* Patients with a diagnosis of congenital S Protein deficiency.
* Patients who are taking oral anticoagulant therapy (TAO) or new oral anticoagulants (NAO).
* Chronic liver failure (> 5 points on the Child-Pugh score).
* Female subjects who are pregnant or on estrogen-progestogen replacement therapy.

• Luisa Verga, MD, Study director, San Gerardo Hospital