Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection

The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblasts susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antivirus drug tests and safety evaluation.

Clinical characteristics and risk factors of patients with systemic lupus erythematosus and cancer / 中华内科杂志

To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without ( P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers ( P<0.01). Correlation analysis revealed significant correlation between disease course of SLE ( OR=4.25, 95% CI 1.79~10.01, P<0.001), hydroxychloroquine ( OR=0.26, 95% CI 0.12~0.59, P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.

Clinical characteristics and risk factors of patients with systemic lupus erythematosus and cancer / 中华内科杂志

To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without (P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers (P<0.01). Correlation analysis revealed significant correlation between disease course of SLE (OR=4.25, 95%CI 1.79~10.01,P<0.001), hydroxychloroquine (OR=0.26, 95%CI 0.12~0.59,P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.