Clinical trial NCT04675281: Pathological Findings of Fatal COVID-19
Official title: Pathological Findings in Critically-ill Patients Who Died From SARS-CoV-2 Related Acute Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SARS-CoV-2
Covid19
Pathology
Intensive Care Units
Respiratory Distress Syndrome
Keywords: SARS-CoV-2
Pneumonia
Intensive care units
Acute Respiratory Distress Syndrome
Histopathology
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: National Research Agency, France
First posted: 2020-12-19
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients deceased in the ICU from a Covid-19 during the study period

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

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

Primary outcomes:
measure: Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU
timeFrame: Two post-mortem lung biopsies performed immediately after death.
Secondary outcomes:
measure: Comparison between early (<1 week after ICU admission) and late (≥1 week) deaths
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Analysis of the influence of ARDS severity and length on pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Analysis of the influence of ARDS severity and length on pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Analysis of the influence of pharmacological treatments (steroids) on pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Analysis of the correlation between radiological findings and pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Association between the primary cause of death and pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Analysis of the correlation between the ventilator settings and pathological findings
timeFrame: Two post-mortem lung biopsies performed immediately after death.
measure: Co-infections
timeFrame: Two post-mortem lung biopsies performed immediately after death.
Other outcomes:
Locations:
city: Amiens
country: France
facility: CH Amiens
city: Angers
country: France
facility: Angers University Hospital
city: Angoulême
country: France
facility: CH Angoulême
city: Annecy
country: France
facility: CH Annecy
city: Antony
country: France
facility: Hopital Privé d'Antony
city: Argenteuil
country: France
facility: CH Argenteuil
city: Belfort
country: France
facility: CH Belfort
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Bry-sur-Marne
country: France
facility: Hopital Sainte Camille
city: Cahors
country: France
facility: CH Cahors
city: Cergy-Pontoise
country: France
facility: CH Cergy Pontoise
city: Cholet
country: France
facility: CH Cholet
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Compiègne
country: France
facility: CH Compiègne-Noyon
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Lyon
country: France
facility: Hopital Lyon Sud
city: Lyon
country: France
facility: Hôpital Lyon Sud
city: Marseillette
country: France
facility: Marseille Hopital Nord APHM
city: Melun
country: France
facility: CH Melun
city: Montélimar
country: France
facility: CH Montélimar
city: Nantes
country: France
facility: Nantes University Hospital
city: Nice
country: France
facility: CHU Nice
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: CH Ambroise Paré APHP
city: Paris
country: France
facility: GHEF Marne La Vallée
city: Paris
country: France
facility: Hopital Antoine Béclère APHP
city: Paris
country: France
facility: Hopital Cochin APHP
city: Paris
country: France
facility: Hopital Georges Pompidou APHP
city: Paris
country: France
facility: Hopital La Pitié Salpetrière APHP
city: Paris
country: France
facility: Hopital Louis Mourier APHP
city: Paris
country: France
facility: Hopital Necker APHP
city: Paris
country: France
facility: Hopital Saint-Antoine APHP
city: Paris
country: France
facility: Hopital Saint-Louis APHP
city: Poissy
country: France
facility: CH Poissy
city: Quincy-sous-Sénart
country: France
facility: Hopital Privé Claude Galien
city: Reims
country: France
facility: CH Reims
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Brieuc
country: France
facility: CH Saint-Brieuc
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Suresnes
country: France
facility: Hopital Foch
city: Tours
country: France
facility: CHRU Tours
city: Troyes
country: France
facility: CH Troyes
city: Vannes
country: France
facility: CH Vannes
city: Versailles
country: France
facility: CH Versailles
Study officials:
References: