Pathological Findings of Fatal COVID-19

Covid19 Clinical Trial

— HISTOCOVID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04675281
• Other study ID #: MR_HISTOCOVID
• Status: Completed
• Start date: April 22, 2020
• Est. completion date: March 3, 2021

Study information

• Verified date: November 2023
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: March 3, 2021
• Est. primary completion date: March 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Intensive Care Units
• Pathology
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• SARS-CoV-2
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	National Research Agency, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU	Detailed description and analysis of the primary lesions of the lungs in patients who died in the ICU from Covid-19.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Comparison between early (<1 week after ICU admission) and late (=1 week) deaths	Comparison of pathological findings according to the time between ICU admission and death.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Analysis of the influence of ARDS severity and length on pathological findings	Comparison of pathological findings according to the length of acute respiratory syndrome.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Analysis of the influence of ARDS severity and length on pathological findings	Comparison of pathological findings according to the duration of acute respiratory syndrome.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Analysis of the influence of pharmacological treatments (steroids) on pathological findings	Comparison of pathological findings between patients who received steroids and those who did not.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Analysis of the correlation between radiological findings and pathological findings	Comparison between radiological description of the CT of the lungs and the radiological findings.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Association between the primary cause of death and pathological findings	Analysis of the pathological findings according to the primary cause of death (hypoxia, shock, hypoxia and shock, cardiac arrest, other).	Two post-mortem lung biopsies performed immediately after death.
Secondary	Analysis of the correlation between the ventilator settings and pathological findings	Analysis of the correlation between the ventilator settings (tidal volume, PEEP, driving pressure, plateau pressure, static compliance, volume or pressure mode) and pathological findings.	Two post-mortem lung biopsies performed immediately after death.
Secondary	Co-infections	Description of the co-infection (bacterial or fungal infections) documented by pathological findings	Two post-mortem lung biopsies performed immediately after death.