Bo Diao

Abstract While lymphocytopenia is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169 + macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2 + cells, CD169 + macrophages, but not in CD3 + T cells or B220 + B cells in spleens and LNs. SARS-CoV-2 infection induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy, histiocyte hyperplasia and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue-resident CD169 + macrophages.

Abstract Importance The outbreak of highly contagious COVID-19 has posed a serious threat to human health, especially for those with underlying diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients have not been reported. Objective To summery an outbreak of COVID-19 epidemic in HD center. Design, Setting, and Participants We reviewed the epidemic course from the first laboratory-confirmed case of COVID-19 infection on January 14 to the control of the epidemic on March 12 in the HD center of Renmin Hospital of Wuhan University. Total 230 HD patients and 33 medical staff were included in this study Exposures COVID-19. Main Outcomes and Measures Epidemiological, clinical, laboratory, and radiological characteristics and outcomes data were collected and analyzed. 19 COVID-19 HD patients, 19 non-COVID-19 HD patients and 19 healthy volunteers were enrolled for further study about the effect of SARS-CoV-2 infection on host immune responses. Results 42 out of 230 HD patients (18.26%) and 4 out of 33 medical staffs (12.12%) were diagnosed with COVID-19 from the outbreak to March 12, 2020. 13 HD patients (5.65%), including 10 COVID-19 diagnosed, died during the epidemic. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure. Except 3 patients were admitted to ICU for severe condition (8.11%), including 2 dead, most COVID-19 diagnosed patients presented mild or none-respiratory symptoms. Multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other COVID-19 patients. Conclusions and Relevance HD patients are the highly susceptible population and HD centers are high risk area during the outbreak of COVID-19 epidemic. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

We investigated the correlation between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene methylation and pre-eclampsia, and its clinical significance, by comparing methylation in the MTHFR gene promoter of the placenta and peripheral venous blood in pre-eclampsia and normal gravidas. We enrolled 259 gravidas from the People's Liberation Army 202nd Hospital, China, between January 2011 and September 2011, including 127 pre-eclampsia and 132 nor-mal gravidas. Methylation levels of the MTHFR gene in placentas in two sets of gravidas were detected by methylation-specific polymerase chain reaction, plasma homocysteine levels were detected by enzyme-linked immunosorbent assay, and folic acid and vitamin B12 levels were detected by electrochemiluminescence. The chi-square test results were analyzed using the SPSS19.0 statistical software. In placentas, the methylation indices were 26.8% (34/127) and 15.2% (20/132) in the pre-eclampsia and normal groups, respectively (χ(2) = 5.30, P < 0.05, odds ratio (OR) = 2.04, 95% confidence interval (95%CI) = 1.10-3.73). In peripheral venous blood, the methylation indices were 22.8% (29/127) and 12.1% (16/132) in pre-eclampsia and normal groups, respectively (χ(2) = 5.17, P < 0.05, OR = 2.15, 95%CI = 1.11-4.15). The plasma methylation level of the pre-eclampsia group was consistent with the normal group. The plasma homocysteine level in the pre-eclampsia group was higher than in the normal group (P < 0.05). Levels of folic acid and vitamin B12 in the pre-eclampsia and normal groups were not statistically significant (P > 0.05). Patients with pre-eclampsia have hypermethylation in the MTHFR gene promoter, which may be one of its causes.

OBJECTIVE: To investigate the association of angiotensinogen (AGT) gene polymorphisms and angiogenic factors with preeclampsia (PE) in Chinese women. METHODS: A study on Chinese women was performed. Detection of the M235T polymorphism of AGT gene was carried out by PCR. Using a χ² test, genotype and allele frequencies were compared in all groups. Maternal serum levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt1) at gestation were compared between 92 women with PE and 100 controls by ELISA. RESULTS: Compared to the controls, the AGT homozygous of TT genotype in PE occurred significantly more frequently and the T allele was observed to occur more frequently than the M allele (p < 0.05). sFlt1 was present in high quantities in the serum of women with PE and was associated with low levels of free VEGF and PlGF (p < 0.05). Plasma sFlt1 levels are higher in PE patients with TT heterozygotes compared with MM homozygotes, but PIGF is lower (p < 0.05). Plasma VEGF concentrations showed no significant difference. CONCLUSIONS: Our study showed that AGT M235T polymorphism is associated with PE in Chinese women. Furthermore, the gene polymorphism of the components of the renin-angiotensin system may contribute to the concentration alterations of sFlt1, VEGF, and PlGF in maternal serum, which causes disordered vasculogenesis contributing to PE.