SARS-CoV-2 can infect human embryos
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- Evaluated articles (Rapid Reviews Infectious Diseases)
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. By using RNA-seq and immunofluorescence, 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. For the purpose of viral entry studies, we used fluorescent reporter virions pseudotyped with Spike (S) glycoprotein from SARS-CoV-2, and we observe robust infection of trophectoderm cells. 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
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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.
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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.
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Strength of evidence
Reviewers: Giovanni Piedimonte (Tulane University) | 📒📒📒 ◻️◻️
Rana Chakraborty (Mayo Clinic) | 📒📒📒◻️◻️ -
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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 Statement Consent: 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. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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-TMPRSS2suggested: NoneThe following secondary Alexa Fluor-conjugated antibodies (Invitrogen) were used at a dilution of … 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 Statement Consent: 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. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 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-TMPRSS2suggested: NoneThe 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-goatsuggested: Noneanti-mousesuggested: (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-ACE2suggested: Noneanti-SARSsuggested: Noneanti-Human IgGsuggested: (Bio-Rad Cat# STAR127, RRID:AB_1102708)Experimental Models: Cell Lines Sentences Resources 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. 293Tsuggested: NoneSoftware and Algorithms Sentences Resources 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. STARsuggested: (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.
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