The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

Chadchan, Sangappa B.; Maurya, Vineet Kumar; Popli, Pooja; Kommagani, Ramakrishna

doi:10.1101/2020.06.23.168252

Cited by 14 publications

(13 citation statements)

References 46 publications

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“…Studies on animal models have described weak expression of ACE2 in endometrial cells of pregnant rats [ 29 ]. Expression of ACE2 in human endometrial cells in pregnancy is not described yet; however, first reports on ACE2 expression in the endometrium are currently being published [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion

Mertz²,

et al. 2020

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Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.

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Section: Discussionmentioning

confidence: 99%

Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion

Mertz²,

et al. 2020

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“…It is recognized that SARS-CoV-2 uses ACE2 as a receptor for cellular entry and TMPRSS2 protease for viral Spike protein priming (25,26). The intestinal enterocytes have a higher expression of ACE2 compared to alveolar epithelial type II cells (27)(28)(29). Among the tested three cell lines in this work, ACE2 and TMPRSS2 were expressed at the highest level in Caco-2 cells (Fig.…”

Section: Sars-cov-2 Infection In the Intestine-on-chipmentioning

confidence: 69%

Modeling SARS-CoV-2 infectionin vitrowith a human intestine-on-chip device

Guo

Luo

Wang

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has given rise to a global pandemic. The gastrointestinal symptoms of some COVID-19 patients are underestimated. There is an urgent need to develop physiologically relevant model that can accurately reflect human response to viral infection. Here, we report the creation of a biomimetic human intestine infection model on a chip system that allows to recapitulate the intestinal injury and immune response induced by SARS-CoV-2, for the first time. The microengineered intestine-on-chip device contains human intestinal epithelium (co-cultured human intestinal epithelial Caco-2 cells and mucin secreting HT-29 cells) lined in upper channel and vascular endothelium (human umbilical vein endothelial cells, HUVECs) in a parallel lower channel under fluidic flow condition, sandwiched by a porous PDMS membrane coated with extracellular matrix (ECM). At day 3 post-infection of SARS-CoV-2, the intestine epithelium showed high susceptibility to viral infection and obvious morphological changes with destruction of intestinal villus, dispersed distribution of mucus secreting cells and reduced expression of tight junction (E-cadherin), indicating the destruction of mucous layer and the integrity of intestinal barrier caused by virus. Moreover, the endothelium exhibited abnormal cell morphology with disrupted expression of adherent junction protein (VE-cadherin). Transcriptional analysis revealed the abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., up-regulated cytokine genes, TNF signaling and NF-kappa B signaling-related genes). This bioengineered in vitro model system can mirror the human relevant pathophysiology and response to viral infection at the organ level, which is not possible in existing in vitro culture systems. It may provide a promising tool to accelerate our understanding of COVID-19 and devising novel therapies.

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“…Consistent with these previous studies, our findings in the current case showed a close association between symptoms, positive RT‐PCR test results and the menstruation. This phenomenon might be partly explained by the findings of Chadchan et al 16 They found that the expression of angiotensin converting enzyme 2 (ACE2), by which SARS‐CoV‐2 enters human cells, is high in human endometrial stroma and increases in the secretory phase. Furthermore, ACE2 expression in human endometrial stroma is promoted by progesterone.…”

Section: Discussionmentioning

confidence: 99%

Changes in RT‐PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS‐CoV‐2: Report of two cases

Zheng

Tan

et al. 2020

Journal of Medical Virology

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The implications of the menstrual cycle for disease susceptibility, development, and severity of acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are largely unknown. Here, we describe two women infected with SARS‐CoV‐2 whose real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) test results and symptoms changed during the menstrual cycle. The first patient developed a fever on the first day of her menstrual period, and again on the first day of her next menstrual period after hospital discharge. RT‐PCR test results were positive during the first menstrual period before admission, but turned negative during hospitalization, and then were positive again during the second menstrual period after hospital discharge. Another one also developed a fever again on the first day of her menstrual period after hospital discharge. RT‐PCR test results were negative before admission and during hospitalization, but turned positive during the first menstrual period after hospital discharge. The cases indicate sex hormones may play an important role in SARS‐CoV‐2 infection. For women with history of exposure to SARS‐CoV‐2, the management protocol should include assessment of the menstrual status.

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The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

Cited by 14 publications

References 46 publications

Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion

Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion

Modeling SARS-CoV-2 infectionin vitrowith a human intestine-on-chip device

Changes in RT‐PCR test results and symptoms during the menstrual cycle of female individuals infected with SARS‐CoV‐2: Report of two cases

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