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NCT Number: NCT04675281

Pathological Findings of Fatal COVID-19

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

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Key information

Conditions

SARS-CoV-2 COVID-19 Coronaviridae Infections Coronavirus Infections Covid19 Infections Intensive Care Units Lung Diseases Nidovirales Infections Pathology Pneumonia Pneumonia, Viral RNA Virus Infections Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CH Amiens, Amiens, France

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Other

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.

Primary outcomes

  1. Analysis of the pathological findings of a large cohort of patients who died from COVID-19 in the ICU

    Time frame: 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 outcomes

  1. Comparison between early (<1 week after ICU admission) and late (≥1 week) deaths

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Comparison of pathological findings according to the time between ICU admission and death.

  2. Analysis of the influence of ARDS severity and length on pathological findings

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Comparison of pathological findings according to the length of acute respiratory syndrome.

  3. Analysis of the influence of ARDS severity and length on pathological findings

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Comparison of pathological findings according to the duration of acute respiratory syndrome.

  4. Analysis of the influence of pharmacological treatments (steroids) on pathological findings

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Comparison of pathological findings between patients who received steroids and those who did not.

  5. Analysis of the correlation between radiological findings and pathological findings

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Comparison between radiological description of the CT of the lungs and the radiological findings.

  6. Association between the primary cause of death and pathological findings

    Time frame: 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).

  7. Analysis of the correlation between the ventilator settings and pathological findings

    Time frame: 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.

  8. Co-infections

    Time frame: Two post-mortem lung biopsies performed immediately after death.

    Description of the co-infection (bacterial or fungal infections) documented by pathological findings

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Collaborators

  • National Research Agency, France

Registry information

Official study title

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

Acronym: HISTOCOVID

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Dec 19, 2020
Registry last updated
Nov 30, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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