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
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
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.
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
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
CANET Emmanuel
02-40-08-31-61
emmanuel.canet@chu-nantes.fr
MORIN Jean
jean.morin@chu-nantes.fr