ABSTRACT
Objective:To fully understand the maternal and neonatal outcomes in pregnant women with COVID-19 and explore the evidence of intrauterine vertical transmission of 2019-nCoV by analyzing clinical and laboratory information in peer-reviewed publications on COVID-19 in pregnant women.Methods:PubMed, Embase, China National Knowledge Infrastructure, China Academic Journals, and Wanfang Databases were searched to retrieve articles on COVID-19 in pregnancy published from December 1, 2019, to April 9, 2020. In addition, the World Health Organization COVID-19 Database and the reference lists in each included article were also searched. All included cases were positive for 2019-nCoV nucleic acid with maternal and neonatal outcomes regardless of delivery or not. Clinical manifestations, perinatal and neonatal outcomes were analyzed systematically.Results:This study reviewed 29 publications involving 146 pregnant women who tested positive for 2019-nCoV nucleic acid and their 116 newborns (including two twins). Five cases of severe COVID-19 and three cases of unidentified type that were admitted to ICU for treatment were severe symptoms, accounting for 5.5% (8/146) of all cases. Totally, 69.9% (102/146) of the women underwent cesarean section and 8.2% (12/146) gave birth vaginally. Thirty (20.5%) women continued their pregnancies. One case (0.7%, 1/146) terminated the pregnancy at 26 weeks of gestation due to bidirectional affective disorder and one (0.7%, 1/146) received artificial abortion at 6 weeks of gestation. Fever (58.2%, 85/146) and cough (32.9%, 48/146) were the most common symptoms. However, 15.8% (23/146) of the pregnant women were asymptomatic on admission and symptoms appeared or became worse after delivery in 20.5% (30/146). Lymphocytopenia (49.6%, 56/113) and elevated C-reactive protein (58.4%, 66/113) were the main laboratory findings. The most common computed tomography (CT) finding was bilateral multiple patchy ground-glass opacity in lungs (79.7%, 94/118). The outcomes of 92.2% (107/116) of the newborns were good, and the rest 7.8% (9/116) showed different abnormalities of varying degrees. Among the nine newborns, six showed different degrees of dyspnea, cyanosis and vomiting including one died of multiple organ failure and disseminated intravascular coagulation; one tested positive for viral nucleic acid 36 hours after birth; one was stillbirth due to unknown reason, but intrauterine vertical transmission was excluded; one neonatal death in a critically ill mother undergoing cesarean delivery.Conclusions:Pregnant women are less likely to progress to severe COVID-19 and mostly have a good outcome. Despite reports of adverse neonatal outcomes, evidence of intrauterine vertical transmission of 2019-nCoV remains insufficient.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanisms of lysophosphatidic acid (LPA) in stimulating invasion and metastatic colonization of ovarian cancer cells.</p><p><b>METHODS</b>The metastatic ability in vivo of ovarian cancer SK-OV3, HEY, OVCAR3, and IGROV1 cells was determined in tumor-bearing nude mouse models. Matrigel assay was used to detect the changes of response in vitro of ovarian cancer cells to LPA after Rac(-) or Rac(+) adenovirus treatment. LPA-induced Rho GTPase activation was detected by GST-fusion protein binding assay.</p><p><b>RESULTS</b>The peritoneal metastatic colonization assay showed overt metastatic colonization in mice receiving SK-OV3 and HEY cell inoculation, indicating that they are invasive cells. Metastatic colonization was not detected in animals receiving OVCAR3 and IGROV1 cells, indicating that these cells are non-invasive cells. In the matrigel invasion assay, exposure to LPA led to a notably greater migratory response in metastatic SK-OV3 and HEY cells (Optical density: SK-OV3 cells: 0.594±0.023 vs. 1.697±0.049, P<0.01; HEY cells: 0.804±0.070 vs. 1.851±0.095, P<0.01). But LPA did little in the non-metastatic OVCAR3 and IGROV1 cells (Optical density A: OVCAR3 cells: 0.336±0.017 vs. 0.374±0.007, P>0.05; IGROV1 cells: 0.491±0.036 vs. 0.479±0.061, P>0.05). LPA migratory responses of ovarian cancer cells were closely related to their metastatic colonization capabilities (r = 0.983, P<0.05). Rac(-) blocked the LPA response of invasive SK-OV3 and HEY cells (LPA-induced fold increase of cell migration: SK-OV3 cells: 2.988±0.095 vs. 0.997±0.100,P=0.01; HEY cells: 2.404±0.059 vs. 0.901±0.072, P=0.01). But Rac(+) confered the non-invasive cells with LPA response and invasion capability (LPA-induced fold increase of cell migration: OVCAR3 cells: 1.072±0.080 vs. 1.898±0.078, P<0.01; IGROV1 cells: 1.002±0.044 vs. 2.141±0.057, P<0.05). Among Rho GTPases, only Rac activation was different between ovarian cancer cell lines with different metastatic capability after LPA stimulation: Cdc42 could not be activated in both the invasive and non-invasive cell lines. RhoA could be activated in both the invasive and non-invasive cell lines. Rac could be activated by LPA in the invasive ovarian cancer cell lines. However, Rac could not be activated in the non-invasive cell lines.</p><p><b>CONCLUSION</b>Lysophosphatidic acid stimulates invasion and metastasis of ovarian cancer cells through Rac activation.</p>