BACKGROUND: SARS-CoV-2 binding receptor ACE2 and the spike protein priming protease TMPRSS2 are co-expressed 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 (an alternative entry receptor) by qPCR in 105 placentae : 45 from pregnant women with HIV (WHIV) exposed to 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 as 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 .
DISCUSSION: We have identified pregnant women of Black race and WHIV who are on PI-based ART to have relatively lower expression of placental ACE2 than those of White race and HIV-uninfected women . This effect may potentially contribute to altered susceptibility to COVID-19 in these women, either favorably; by reduced viral entry, or detrimentally; by loss of ACE2 protection against hyperinflammation.