HISTOCOVID: Pathological Findings of Fatal COVID-19

Sponsor

Nantes University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04675281

Collaborator

National Research Agency, France (Other)

170

Enrollment

Locations

Anticipated Duration (Months)

3.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
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

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

Study Design

Study Type:

Observational

Anticipated Enrollment :

170 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 24, 2020

Actual Primary Completion Date :

Feb 26, 2021

Anticipated Study Completion Date :

Jun 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Critically-ill adult patients who died in the Intensive Care Unit from a documented COVID-19	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.

Arm

Intervention/Treatment

Critically-ill adult patients who died in the Intensive Care Unit from a documented COVID-19

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.

Outcome Measures

Primary Outcome Measures

Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU [Two post-mortem lung biopsies performed immediately after death.]
Detailed description and analysis of the primary lesions of the lungs in patients who died in the ICU from Covid-19.

Secondary Outcome Measures

Comparison between early (<1 week after ICU admission) and late (≥1 week) deaths [Two post-mortem lung biopsies performed immediately after death.]
Comparison of pathological findings according to the time between ICU admission and death.
Analysis of the influence of ARDS severity and length on pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Comparison of pathological findings according to the length of acute respiratory syndrome.
Analysis of the influence of ARDS severity and length on pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Comparison of pathological findings according to the duration of acute respiratory syndrome.
Analysis of the influence of pharmacological treatments (steroids) on pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Comparison of pathological findings between patients who received steroids and those who did not.
Analysis of the correlation between radiological findings and pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Comparison between radiological description of the CT of the lungs and the radiological findings.
Association between the primary cause of death and pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Analysis of the pathological findings according to the primary cause of death (hypoxia, shock, hypoxia and shock, cardiac arrest, other).
Analysis of the correlation between the ventilator settings and pathological findings [Two post-mortem lung biopsies performed immediately after death.]
Analysis of the correlation between the ventilator settings (tidal volume, PEEP, driving pressure, plateau pressure, static compliance, volume or pressure mode) and pathological findings.
Co-infections [Two post-mortem lung biopsies performed immediately after death.]
Description of the co-infection (bacterial or fungal infections) documented by pathological findings

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CH Amiens	Amiens	France
2	Angers University Hospital	Angers	France
3	CH Angoulême	Angoulême	France
4	CH Annecy	Annecy	France
5	Hopital Privé d'Antony	Antony	France
6	CH Argenteuil	Argenteuil	France
7	CH Belfort	Belfort	France
8	CHU Bordeaux	Bordeaux	France
9	Hopital Sainte Camille	Bry-sur-Marne	France
10	CH Cahors	Cahors	France
11	CH Cergy Pontoise	Cergy-Pontoise	France
12	CH Cholet	Cholet	France
13	CHU Clermont-Ferrand	Clermont-Ferrand	France
14	CH Compiègne-Noyon	Compiègne	France
15	CHD Vendée	La Roche-sur-Yon	France
16	Hopital Lyon Sud	Lyon	France
17	Hôpital Lyon Sud	Lyon	France
18	Marseille Hopital Nord APHM	Marseillette	France
19	CH Melun	Melun	France
20	CH Montélimar	Montélimar	France
21	Nantes University Hospital	Nantes	France	44000
22	CHU Nice	Nice	France
23	CHR Orléans	Orléans	France
24	CH Ambroise Paré APHP	Paris	France
25	GHEF Marne La Vallée	Paris	France
26	Hopital Antoine Béclère APHP	Paris	France
27	Hopital Cochin APHP	Paris	France
28	Hopital Georges Pompidou APHP	Paris	France
29	Hopital La Pitié Salpetrière APHP	Paris	France
30	Hopital Louis Mourier APHP	Paris	France
31	Hopital Necker APHP	Paris	France
32	Hopital Saint-Antoine APHP	Paris	France
33	Hopital Saint-Louis APHP	Paris	France
34	CH Poissy	Poissy	France
35	Hopital Privé Claude Galien	Quincy-sous-Sénart	France
36	CH Reims	Reims	France
37	CHU Rennes	Rennes	France
38	CH Saint-Brieuc	Saint-Brieuc	France
39	CHU Saint-Etienne	Saint-Étienne	France
40	Hopital Foch	Suresnes	France
41	CHRU Tours	Tours	France
42	CH Troyes	Troyes	France
43	CH Vannes	Vannes	France
44	CH Versailles	Versailles	France