Early postmortem brain MRI findings in COVID-19 non-survivors

  1. Tim Coolen
  2. Valentina Lolli
  3. Niloufar Sadeghi
  4. Antonin Rovaï
  5. Nicola Trotta
  6. Fabio Silvio Taccone
  7. Jacques Creteur
  8. Sophie Henrard
  9. Jean-Christophe Goffard
  10. Olivier De Witte
  11. Gilles Naeije
  12. Serge Goldman
  13. Xavier De Tiège

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Abstract

Importance

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak.

Objective

To investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.

Design

Prospective, case series study with postmortem brain MRI obtained early (<24h) after death.

Setting

Monocentric study.

Participants

From 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility.

Main Outcome(s) andMeasure(s)

Signs of acute brain injury and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians.

Results

Among the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality.

Conclusions and Relevance

Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress in COVID-19.

Key Points

Question

Is there common brain MRI abnormalities patterns in non-survivors of coronavirus disease 2019 ?

Findings

In a case series of 19 non-survivors of severe COVID-19 disease, early postmortem brain MRI demonstrated patterns evocative of intracranial vasculopathy in 4 decedents: subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent). Asymmetric olfactory bulbs were found in 4 other decedents but without downstream olfactory tract abnormalities.

Meaning

Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by virus-induced endothelial disturbances.

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    SciScore for 10.1101/2020.05.04.20090316: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Study Design and participants: This study was carried out at the CUB Hôpital Erasme (Brussels, Belgium) after approval by the institutional Ethical Committee (Ref: P2020/204, SRB2020121), which did not request informed consent from legal representatives.
    Consent: Study Design and participants: This study was carried out at the CUB Hôpital Erasme (Brussels, Belgium) after approval by the institutional Ethical Committee (Ref: P2020/204, SRB2020121), which did not request informed consent from legal representatives.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Further discussion and study limitations are available in eDiscussion. In summary, this postmortem MRI study demonstrated the occurrence of vasculopathic brain lesions in COVID-19 non-survivors that might be triggered by the endothelial disturbances associated with SARS-CoV-2 infection.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.05.04.20090316v1 on medRxiv