ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy-Implications for SARS-CoV-2 Placental Infection

J Infect Dis. 2021 Dec 8;224(Supplement_6):S631-S641. doi: 10.1093/infdis/jiab166.


Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding receptor ACE2 and the spike protein priming protease TMPRSS2 are coexpressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART).

Methods: We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2, and L-SIGN by quantitative polymerase chain reaction in 105 placentae: 45 from pregnant women with HIV (WHIV) on protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women.

Results: ACE2 levels were lower, while L-SIGN levels were higher, in placentae from WHIV on PI-based ART compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses.

Conclusions: We identified pregnant women of black race and WHIV on PI-based ART to have relatively lower expression of placental ACE2 than those of white race and HIV-uninfected women. This may potentially contribute to altered susceptibility to COVID-19 in these women, favorably by reduced viral entry or detrimentally by loss of ACE2 protection against hyperinflammation.

Keywords: AIDS; COVID-19; HIV protease inhibitors; detrimental; infant sex; neonate; placenta; race; receptor; renin-angiotensin system.

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Antiretroviral Therapy, Highly Active
  • COVID-19* / diagnosis
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Female
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Placenta / metabolism*
  • Pregnancy
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • SARS-CoV-2 / physiology*
  • Serine Endopeptidases / genetics*


  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • HIV Protease Inhibitors
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Cell Surface
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human