Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients

  1. Myriam Remmelink
  2. Ricardo De Mendonça
  3. Nicky D’Haene
  4. Sarah De Clercq
  5. Camille Verocq
  6. Laetitia Lebrun
  7. Philomène Lavis
  8. Marie-Lucie Racu
  9. Anne-Laure Trépant
  10. Calliope Maris
  11. Sandrine Rorive
  12. Jean-Christophe Goffard
  13. Olivier De Witte
  14. Lorenzo Peluso
  15. Jean-Louis Vincent
  16. Christine Decaestecker
  17. Fabio Silvio Taccone
  18. Isabelle Salmon

Reviewed by

Read the full article

Listed in

Log in to save this article

Abstract

Background

Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients.

Methods

We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs.

Results

Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain).

Conclusions

In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.

Article activity feed

  1. Version published to 10.1186/s13054-020-03218-5
  2. ScreenIT

    SciScore for 10.1101/2020.05.27.20114363: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Exclusion criteria were lack of family consent and a delay of more than five days after death.
    IRB: The study protocol was approved by the local ethics committee (P2020/218).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 detection by immunohistochemistry: Since no antibody against SARS-CoV-2 has been validated for IHC on FFPE tissues, we selected an anti-SARS-nucleocapsid protein antibody.
    SARS-CoV-2
    suggested: None
    anti-SARS-nucleocapsid protein
    suggested: None
    Software and Algorithms
    SentencesResources
    All data were analyzed using GraphPad Prism Version 8.4.2
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    (GraphPad Software, San Diego, CA, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    The limitation of lung biopsy was also shown in another study, in which only 50% of lung samples were positive for SARS-CoV-2 using RT-PCR (21), when compared to almost 100% in our series. In addition, we did not find specific “endothelitis” as previously reported in a small case series (4). Considering the heterogeneity of post-mortem COVID-19 associated lesions, molecular and IHC assessment are mandatory in the histological analysis of COVID-19 tissue samples. Patients with COVID-19 often have altered coagulation and a prothrombotic status, with the possible development of acute pulmonary embolism (PE) (22). In our study, three patients had PE, already diagnosed before death. Four patients had pulmonary infarction. In a previous study, acute PE was considered as the main cause of death in four patients (3); however, the inclusion of patients who died before hospital admission and the lack of specific thromboprophylaxis during the hospital stay may account for the differences in the severity of PE when compared to our study. Although we frequently observed the presence of microthrombi in the lung parenchyma, this feature is also reported in other forms of ARDS, regardless of etiology (13, 23). As such, whether diffuse pulmonary thrombosis is a main contributor of the fatal course of severe hypoxemia in COVID-19 patients remains to be further studied. We did not observe specific viral organ injury, such as myocarditis, hepatitis or encephalitis. The cases of “acute cardiac in...

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • 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.

  3. Version published to 10.1101/2020.05.27.20114363v1 on medRxiv