High Expression of ACE2 and TMPRSS2 at the Resection Margin Makes Lung Cancer Survivors Susceptible to SARS-CoV-2 with Unfavorable Prognosis (preprint)

Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Systematic analysis of lung cancer survivors at molecular and clinical levels is warranted to understand the disease course and clinical characteristics. We performed a retrospective study of 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. Duringtreatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 had a shorter median time from symptom onset to hospitalization (P=0.016) and longer clinical symptom remission time (P=0.020) than non-cancer individuals. No differences were observed among indicators such as time from symptom onset to hospitalization and symptom remission time between long-term and short-term survivors. The expression of ACE2(P=0.013) and TMPRSS2(P<0.001) was elevated in lung cancer survivors as compared with that in non-cancer individuals.

Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of &#945;-synuclein (&#945;-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of &#945;-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P <0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of &#945;-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.

Systematic investigations of COVID-19 in 283 cancer patients (preprint)

Background: Cancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and Participants: Data of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. Results: A total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. Conclusions: This is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.

Vaginal delivery after 37 days of a convalescent pregnant woman with COVID-19: a case report / 中华围产医学杂志

We present a case report of a healthy neonate born by vaginal delivery to a woman who had recovered from COVID-19 after 37 days of discharge. The pregnant woman had fever, cough, and chills at 33 +1 gestational weeks and was diagnosed with COVID-19 by coronavirus nucleic acid test one day later. She recovered and was discharged after a series of treatment, and the 2019 novel coronavirus nucleic acid test and pulmonary CT were negative at the 2nd and 4th weeks after being discharged. The patient was admitted in early labor at 38 +4 gestational weeks and delivered a healthy newborn vaginally at that day. Both the mother and the baby were in good condition. All the maternal or neonatal specimens taken immediately after birth in the delivery room for 2019 novel coronavirus nucleic acid tests were negative, including the maternal pharynx, rectal and cervical secretions, amniotic fluid, an neonatal pharynx and rectal swabs. The qualitative examination of 2019 novel coronavirus antibodies in the maternal venous blood test showed that both IgG and IgM were positive. While the same test for neonatal cord blood and femoral vein blood showed negative results. No inflammatory reaction was found in the placenta and immunohistochemistry detection of novel coronavirus N protein was negative. The mother and newborn were observed postnatally and treated in the same ward, neither of them had fever, cough or fatigue, and were discharged three days after delivery. The qualitative examination of 2019 novel coronavirus antibodies (IgM and IgG) in the femoral vein blood of the nenonate 27 days old showed negative results.

Electrical probing of COVID-19 spike protein receptor binding domain via a graphene field-effect transistor (preprint)

Here, in an effort towards facile and fast screening/diagnosis of novel coronavirus disease 2019 (COVID-19), we combined the unprecedently sensitive graphene field-effect transistor (Gr-FET) with highly selective antibody-antigen interaction to develop a coronavirus immunosensor. The Gr-FET immunosensors can rapidly identify (about 2 mins) and accurately capture the COVID-19 spike protein S1 (which contains a receptor binding domain, RBD) at a limit of detection down to 0.2 pM, in a real-time and label-free manner. Further results ensure that the Gr-FET immunosensors can be promisingly applied to screen for high-affinity antibodies (with binding constant up to 2*10^11 M^-1 against the RBD) at concentrations down to 0.1 pM. Thus, our developed electrical Gr-FET immunosensors provide an appealing alternative to address the early screening/diagnosis as well as the analysis and rational design of neutralizing-antibody locking methods of this ongoing public health crisis.