COVID-19 Associated Endothelial Dysfunction Study

SARS-CoV-2 enters human cells through the binding of the spike protein with angiotensin converting enzyme-2 (ACE2), a membrane receptor highly expressed in immune or non-immune cells, and in many organs, including lungs and endothelial cells.

In COVID-19 disease, the infection of endothelial might cause an acute endothelial dysfunction.

The objective of this study is to demonstrate that patients COVID19 (+) hospitalized in ICU present an acute endothelial dysfunction (compared with COVID19 (-) also hospitalized in ICU).

This acute endothelial dysfunction could lead to organ failure, systemic immune dysregulation and thrombosis.

This cohort study compares 3 exposure cohorts :

Cohort C1 includes COVID19 (+) patients admitted in ICU in whom the diagnosis of COVID19 pneumonia was confirmed.

Cohort C2 includes COVID 19 (-) matched patients also admitted in ICU.

Cohort C3 is a control group. Patients with few comorbidities, ASA 1, recruited during preoperative assessment for elective surgery.

Eligible patients are included within 72 hours of ICU admission (C1, C2) or during the preoperative assessment (C3). Oral consent is needed after complete explanation of the protocol.

During inclusion visit (V0), patient characteristics as treatments, medical history, clinical and biological data are registered.

Microcirculation is assessed for each patient directly after inclusion.

For patients in C1 and C2 a follow-up is planned. This visit (V1) occurs when the patient is discharged from ICU or the day of his death if it occurs in ICU. In case of prolonged stay in ICU, V1 is carried out 2 months after inclusion. During V1, arterial and/or venous thromboembolic events and mortality in ICU is registered.

For Patients in C3, no follow-up is planned.

Eligibility Criteria:
Inclusion criteria :

* Adult patient (≥ 18 ans)
* Affiliation to the French National Healthcare System
* Voluntary patient who have given oral consent

Cohort C1, COVID19 (+) patients hospitalized in ICU :

* Patient admitted to ICU within 72 hours before inclusion
* Patient presenting SARS-COV2 pneumonia diagnosed by CT scan or by COVID-19 PCR test.

Cohort C2, COVID19 (-) patients hospitalized in ICU :

* Patient admitted to ICU within 72 hours before inclusion
* All COVID19 PCR tests carried out in the 15 days prior inclusion are negative
* All the CT scans possibly performed since the acute event do not show COVID19 pulmonary lesions
* Matching with the cases C1 COVID 19 (+) patients on sex, age (threshold at 65 years), treated hypertension, treated diabetes mellitus.

Cohort C3, elective surgery patients who are not hospitalized in ICU :

* ASA 1 classification (no major comorbidity, a normaly healthy patient)
* Asymptomatic to COVID19 according to French Anesthesiology Society 2020 :

  * No major symptoms among : measured fever \> 38°C, dry cough, shortness of breath or high respiratory rate (\>20/min), anosmia, ageusia
  * No more than one minor symptom among : sore throat, rhinorrhea, chest pain, myalgia, general alteration or severe tiredness, confusion, disorientation, headache, diarrhea, nausea or/and vomiting, rash/ frostbite/cracking on fingers or hand
* No positive COVID19 PCR test within 15 days prior to inclusion

Non-inclusion criteria :

* Proven sepsis (Procalcitonin \>1.0 µg/l) in the 24 hours prior to inclusion
* End-stage kidney disease with dialysis
* Patient with haemodynamic failure treated by norepinephrine
* Patient with traumatic brain injury
* Intubated patient and/or sedated
* Pregnant woman, parturient and nursing mother
* Person restricted in liberty by an administrative or judicial decision
* Patient concerned with admission for psychiatric care
* Adult person subject to a legal protection measure or unable to express consent

Exclusion criteria :

• Cohorts C2 and C3 : positive COVID-19 PCR test within 5 days after inclusion