Minimal Invasive Autopsies to Investigate Changes in Deceased COVID-19 Patients (MIA-COVID-19)

Increasing Our Understanding of COVID-19: Minimal Invasive Autopsies to Investigate Clinical, Radiological, Microbiological and Histopathological Changes in Deceased COVID-19 Patients

Rationale In a very short time corona virus disease 2019 (COVID-19) has become a pandemic with high morbidity and mortality. The main cause of death is respiratory failure including acute respiratory distress syndrome, however the exact mechanisms and other underlying pathology is currently not yet known. In the current setting of the COVID-19 pandemic complete autopsies seem too risky due to the risk of SARS CoV-2 transmission. Yet, as so little is known, additional histopathological, microbiological and virologic study of tissue of deceased COVID-19 patients will provide important clinical and pathophysiological information. Minimal invasive autopsy combined with postmortem imaging seems therefore an optimal method combining safety on the one hand yet proving significant information on the other.

This study aims to determine the cause of death and attributable conditions in deceased COVID-19 patients. This will be performed using post-mortem CT-scanning plus CT-guided MIA to obtain tissue for further histological, microbiological and pathological diagnostics. In addition, the pathophysiology of COVID-19 will be examined by further tissue analysis.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Procedure: CT-scan with minimal invasive autopsy

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium
    • Jessa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients with COVID-19 that die during hospitalization in Jessa hospital. COVID-19 is defined as either a positive SARS CoV-2 PCR result OR a high clinical suspicion combined with typical radiologic findings in the absence of an alternative explanation for the clinical picture.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of cause of death and contributing factors based on clinical, radiological, microbiological and histopathological data of the deceased patient	For each individual patient the cause of death and contributing factors will be assessed. For each individual these diagnoses will be made during a meeting of a multidisciplinary team consisting of at least an infectious diseases physician, a radiologist and a pathologist. On a case to case basis, additional medical specialists can be asked to attend, including an intensive care specialist, a geriatrician and/or a microbiologist. During the meetings, the clinical, radiological, microbiological and histopathological data will be presented to all attending specialists. The final diagnoses will be based on consensus. Outcomes will be reported as proportions with a 95% confidence interval.	up to one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detailed description of the postmortem radiological changes induced by COVID-19	The radiological findings will be systematically scored as absent or present. These findings will be reported as proportions with a 95% confidence interval.	up to one month
Detailed description of the postmortem histopathological changes induced by COVID-19	On the basis of clinical observations at this moment in time correlations will be done between the renal histology findings of the patients with and without renal failure at death as well as between the cardiac histology findings of the patients with and without clinical signs of myocarditis. However, in the light of continuous clinical observations and new insights, this may be expanded in the future. Outcomes will be reported as proportions with a 95% confidence interval.	up to one month
Postmortem quantity of viral RNA	Describe the quantity of viral RNA in the different tissues and relate this to the clinical, radiological and histopathological findings.	up to one month
Postmortem disease mechanisms at cellular level	Study in detail the disease mechanisms at cellular level (including ACE-2 receptor expression in relation to quantity of viral RNA) in the different tissues.	up to one month

Collaborators and Investigators

• Sponsor: Jessa Hospital
• Collaborators: Hasselt University; University Hospital, Antwerp
• Investigators: Principal Investigator: Janneke Cox, MD, PhD, Jessa Hospital

Publications and helpful links

General Publications

• Van Cleemput J, van Snippenberg W, Lambrechts L, Dendooven A, D'Onofrio V, Couck L, Trypsteen W, Vanrusselt J, Theuns S, Vereecke N, van den Bosch TPP, Lammens M, Driessen A, Achten R, Bracke KR, Van den Broeck W, Von der Thusen J, Nauwynck H, Van Dorpe J, Gerlo S, Maes P, Cox J, Vandekerckhove L. Organ-specific genome diversity of replication-competent SARS-CoV-2. Nat Commun. 2021 Nov 16;12(1):6612. doi: 10.1038/s41467-021-26884-7. Erratum In: Nat Commun. 2022 Oct 21;13(1):6247.
• D'Onofrio V, Donders E, Vanden Abeele ME, Dubois J, Cartuyvels R, Achten R, Lammens M, Dendooven A, Driessen A, Augsburg L, Vanrusselt J, Cox J. The clinical value of minimal invasive autopsy in COVID-19 patients. PLoS One. 2020 Nov 11;15(11):e0242300. doi: 10.1371/journal.pone.0242300. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 28, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; pathophysiology; cause of death
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: JessaH_COVID-19_MIA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No