Human Blastocyst is Susceptible to SARS-CoV-2 Infection based on Protein Level Examination of Key Entry Factors in Human Oocytes and Early Embryos (preprint)

Objective ACE2, TMPRSS2 and NRP1 are key factors for SARS-CoV-2 infection. Here, we used immunofluorescence to examine the expression patterns of ACE2, TMPRSS2 and NRP1 in human oocytes and different stages of preimplantation embryos to investigated the susceptibility to be infected by SARS-CoV-2.Methods We collected human GV oocytes and different stages of early embryos donated by patients and then performed immunofluorescence followed by confocal microscopy for signals of ACE2, TMPRSS2 and NRP1 proteins in these oocytes and embryos.Results We found that ACE2 was abundant in both inner cell mass and trophectoderm at blastocyst stage, while TMPRSS2 was mainly enriched in trophectoderm. Both of the two factors had faint signal in cleavage embryos and oocytes. In contrast, NRP1 was barely detectable in oocytes or any stage of early embryos. Conclusion Taken together, we propose that human blastocysts, instead of human oocytes and other stages of early embryos, are susceptible to be infected by SARS-CoV-2. Therefore, specific attention should be paid to manipulation of human blastocysts in assisted reproductive technology.

Exogenous coronavirus interacts with endogenous retrotransposon in human cells (preprint)

Background: There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent particularly dangerous coronaviruses are MERS-CoV, SARS-CoV and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. Results: Here, we go deep into transcriptome of MERS-CoV, SARS-CoV and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression through upregulation of TET genes. Similar upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation will lead to increased genome instability and more frequent readthrough from retrotransposon to dysregulate gene expression. People with higher basal level of retrotransposon like cancer patients and aged people will have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed significant amount of chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA, and this may apply for other coronaviruses. Here we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. Conclusions: In summary, we propose that infection of coronaviruses especially SARS-CoV-2 induce retrotransposon activation, formation of chimeric coronavirus-retrotransposon RNA, and elicits more severe symptoms in patients with underlying diseases. More attention may need to be paid to potential harm contributed by retrotransposon dysregulation in treatment of coronavirus-infected patients.