Official Title
Pathological Findings in Critically-ill Patients Who Died From SARS-CoV-2 Related Acute Respiratory Distress Syndrome
Brief Summary

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new coronavirus discovered in December 2019 in Wuhan, China and currently responsible of a worldwide outbreak and the death of more than 55,000 patients in France. The more severe form of COVID-19 disease induces a pneumonia with profound hypoxemia which may require invasive mechanical ventilation. It is estimated that 5% of COVID-19 patients are admitted to the Intensive Care Unit (ICU) for management. Hospital mortality in patients who develop severe acute respiratory distress syndrome (ARDS) ranges between 40% and 60%. The investigators purpose to investigate the pathological findings of COVID-19 patients who died from ARDS in the ICU by doing post-mortem lung biopsies

Detailed Description

Forty-four French ICUs participate to this study with the aim to perform 200 lung biopsies in
100 patients over a 12-month period. This cohort will be the largest pathological database of
COVID-19 patients who developed ARDS. In accordance with the French law, this study has been
approved and registered by the French Agency of Biomedicine and the French Ministry of
Education and Research (#PFS 20-016). Two transcutaneous lung biopsies per patient will be
performed using a 14G needle and anatomical landmarks (1 anterior biopsy and 1 posterior
biopsy). All biopsies will be referred to the Department of Pathology of Nantes university
hospital and analysed by a group of pathologists specialized in lung tissue. The primary
objective is to describe and characterize the lesions of the lung induced by the SARS-CoV-2
infection. The secondary objectives are to correlate the pathological findings with the
patients' demographics, the treatments administered during the ICU stay, the ventilator
settings, to document the percentage of co-infections and their types, compare the
radiographic findings (Chest X-ray and CT-scan of the chest) with the pathological findings,
to compare the pathological findings of early deaths (<1week after ICU admission) versus late
deaths (>1 week). These pathological findings will undoubtedly help to better understand the
pathophysiology of SARS-CoV-2 pneumonia and pave the way to the development of new
therapeutic strategies

Unknown status
SARS-CoV-2
COVID19
Pathology
Intensive Care Units
Respiratory Distress Syndrome

Other: 2 post-mortem transcutaneous lung biopsies (1 anterior ; 1 posterior) using anatomical landmarks

All specimens are fixed with 4% neutral formaldehyde and embedded in paraffin wax in the department of pathology of each participating centre. Afterwards, all samples are sent for analysis to the department of pathology of Nantes university hospital. All biopsies are independently analysed by a group of pathologists who are experts in lung tissue and blinded to clinical information. All biopsies will be analysed using a predetermined semi-quantitative histological scoring grid. The pathologists are asked to assess the degree of: edema, cell necrosis, hyaline membrane formation, proliferation of alveolar type 2 cells, fibrosis, capillary congestion, alveolar edema, neutrophilic infiltration, and microscopic thrombosis. Finally, the following patterns are recorded: exudative diffuse alveolar damage (DAD), proliferative DAD, fibrosis, intra-alveolar haemorrhage, lymphocytic pneumonia, organizing pneumonia, acute fibrinous organizing pneumonia (AFOP), thrombotic microangiopathy.

Eligibility Criteria

Inclusion Criteria:

- Adult patients (Age≥18 years-old)

- Hospitalized in Intensive Care Unit (ICU)

- Dead in the ICU from documented Covid-19 (clinical and radiological signs of pneumonia
with a positive SARS-Cov-2 PCR from the upper or lower respiratory tract)

- Not registered in the national register of refusal of the French Biomedicine Agency

- According to French law, there was no requirement for signed consent, but the
patient's next of kin were informed about the study before enrolment and were given a
letter of information about the study.

Exclusion Criteria:

- Covid-19 not documented by a positive SARS-Cov-2 PCR

- Patient with a positive SARS-Cov-2 PCR but without any signs of pneumonia during the
ICU stay (no clinical and no radiological signs of pneumonia)

- Patient registered in the "national register of refusal" of the French Biomedicine
Agency

- Refusal expressed by the patient's next of kin to participate to the study

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
France
Locations

CH Amiens
Amiens, France

Angers University Hospital
Angers, France

CH Angoulême
Angoulême, France

CH Annecy
Annecy, France

Hopital Privé d'Antony
Antony, France

CH Argenteuil
Argenteuil, France

CH Belfort
Belfort, France

CHU Bordeaux
Bordeaux, France

Hopital Sainte Camille
Bry-sur-Marne, France

CH Cahors
Cahors, France

CH Cergy Pontoise
Cergy-Pontoise, France

CH Cholet
Cholet, France

CHU Clermont-Ferrand
Clermont-Ferrand, France

CH Compiègne-Noyon
Compiègne, France

CHD Vendée
La Roche-sur-Yon, France

Hopital Lyon Sud
Lyon, France

Hôpital Lyon Sud
Lyon, France

Marseille Hopital Nord APHM
Marseillette, France

CH Melun
Melun, France

CH Montélimar
Montélimar, France

Nantes University Hospital
Nantes, France

CHU Nice
Nice, France

CHR Orléans
Orléans, France

CH Ambroise Paré APHP
Paris, France

GHEF Marne La Vallée
Paris, France

Hopital Antoine Béclère APHP
Paris, France

Hopital Cochin APHP
Paris, France

Hopital Georges Pompidou APHP
Paris, France

Hopital La Pitié Salpetrière APHP
Paris, France

Hopital Louis Mourier APHP
Paris, France

Hopital Necker APHP
Paris, France

Hopital Saint-Antoine APHP
Paris, France

Hopital Saint-Louis APHP
Paris, France

CH Poissy
Poissy, France

Hopital Privé Claude Galien
Quincy-sous-Sénart, France

CH Reims
Reims, France

CHU Rennes
Rennes, France

CH Saint-Brieuc
Saint-Brieuc, France

CHU Saint-Etienne
Saint-Étienne, France

Hopital Foch
Suresnes, France

CHRU Tours
Tours, France

CH Troyes
Troyes, France

CH Vannes
Vannes, France

CH Versailles
Versailles, France

Contacts

CANET Emmanuel
02-40-08-31-61
emmanuel.canet@chu-nantes.fr

National Research Agency, France
NCT Number
Keywords
SARS-CoV-2
Pneumonia
Intensive care units
Acute Respiratory Distress Syndrome
Histopathology
MeSH Terms
COVID-19
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Syndrome