SARS-CoV-2 Can Infect Human Embryos

  1. Mauricio Montano
  2. Andrea R. Victor
  3. Darren K. Griffin
  4. Tommy Duong
  5. Nathalie Bolduc
  6. Andrew Farmer
  7. Vidur Garg
  8. Anna-Katerina Hadjantonakis
  9. Alison Coates
  10. Frank L. Barnes
  11. Christo G. Zouves
  12. Warner C. Greene
  13. Manuel Viotti

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Abstract

The spread of SARS-CoV-2 has led to a devastating pandemic, with infections resulting in a range of symptoms collectively known as COVID-19. The full repertoire of human tissues and organs susceptible to infection is an area of active investigation, and some studies have implicated the reproductive system. The effects of COVID-19 on human reproduction remain poorly understood, and particularly the impact on early embryogenesis and establishment of a pregnancy are not known. In this work, we explore the susceptibility of early human embryos to SARS-CoV-2 infection. We note that ACE2 and TMPRSS2, two canonical cell entry factors for SARS-CoV-2, are co-expressed in cells of the trophectoderm in blastocyst-stage preimplantation embryos. Using fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, we observe robust infection of trophectoderm cells, and this permissiveness could be attenuated with blocking antibodies targeting S or ACE2. When exposing human blastocysts to the live, fully infectious SARS-CoV-2, we detected cases of infection that compromised embryo health. Therefore, we identify a new human target tissue for SARS-CoV-2 with potential medical implications for reproductive health during the COVID-19 pandemic and its aftermath.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Rana Chakraborty

    Review 2: "SARS-CoV-2 Can Infect Human Embryos"

    This study seeks to examine the susceptibility of early human embryos to SARS-CoV-2 infection. Although the reviewers find conclusions well substantiated by the experiments, they also find the practical relevance of the study limited, and not in line with epidemiologic data.

  2. Rapid Reviews Infectious Diseases

    Giovanni Piedimonte

    Review 1: "SARS-CoV-2 Can Infect Human Embryos"

    This study seeks to examine the susceptibility of early human embryos to SARS-CoV-2 infection. Although the reviewers find conclusions well substantiated by the experiments, they also find the practical relevance of the study limited, and not in line with epidemiologic data.

  4. Version published to 10.1101/2021.01.21.427501v2 on bioRxiv
  5. ScreenIT

    SciScore for 10.1101/2021.01.21.427501: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Human Embryos: All embryos used in this study were surplus samples from fertility treatment and in vitro fertilization, donated strictly for research by signed informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The following primary antibodies were used: goat anti-ACE2 (R&D Systems AF933, 1:100), mouse anti-TMPRSS2 (Developmental Hybridoma Bank P5H9-A3, 3.2 μg/ml).
    anti-TMPRSS2
    suggested: None
    The following secondary Alexa Fluor-conjugated antibodies (Invitrogen) were used at a dilution of 1:500: donkey anti-goat Alexa Fluor 568 (A10042), donkey anti-mouse Alexa Fluor 488 (A21202).
    anti-goat
    suggested: None
    anti-mouse
    suggested: (Molecular Probes Cat# A-21202, RRID:AB_141607)
    Additional controls included conditions with either 10 μg of anti-ACE2 antibody (AF933, R&D Systems), anti-SARS CoV-2 S Neutralizing antibody (SAD-S35, ACRO) or anti-Human IgG Kappa (STAR 127, Bio-Rad) control antibody.
    anti-ACE2
    suggested: None
    anti-SARS
    suggested: None
    anti-Human IgG
    suggested: (Bio-Rad Cat# STAR127, RRID:AB_1102708)
    Experimental Models: Cell Lines
    SentencesResources
    Pseudotyped Virion Production: For production of HIV-1 NL-43ΔEnv-eGFP SARS CoV-2 S pseudotyped virus particles, 293T cells were plated at 3.75 ×106 cells in a T175 flask.
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Additional controls included conditions with either 10 μg of anti-ACE2 antibody (AF933, R&D Systems), anti-SARS CoV-2 S Neutralizing antibody (SAD-S35, ACRO) or anti-Human IgG Kappa (STAR 127, Bio-Rad) control antibody.
    STAR
    suggested: (STAR, RRID:SCR_015899)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  6. Version published to 10.1101/2021.01.21.427501v1 on bioRxiv