Rejection of Acellular Porcine Corneal Stroma Transplantation During Coronavirus Disease 2019 Pandemic

: To report 2 successfully managed cases of graft rejection with acellular porcine corneal stroma (APCS) transplantation in patients with fungal corneal ulcer. Two patients were diagnosed with fungal corneal ulcer and received APCS transplantation. Graft rejection developed due to the lost follow-up during the period of coronavirus disease 2019 outbreak. Amniotic membranes transplantation and cauterization of neovascularization was performed, respectively. The graft failure resolved successfully after the procedure. To the best of our knowledge, amniotic membranes transplantation and cauterization of new vessels are the firstly reported in treating APCS graft failure. Amniotic membranes transplantation or cauterization of neovascularization appear to be a safe and costeffective method for treating graft failure.

A Potential Impact of SARS-CoV-2 on Pituitary Glands and Pituitary Neuroendocrine Tumors (preprint)

Introduction: Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors (PitNETs) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 infection on the impairment of pituitary glands and the development of PitNETs.Methods: PitNETs tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 and angiotensin II receptor type 1 (AGTR1) were examined by quantitative real-time PCR. Immunohistochemical staining was performed for ACE2 in 69 PitNETs and 3 normal pituitary glands. The primary tumor cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 agonist, with various dose regimens. The pituitary hormones between 43 patients with SARS-CoV-2 infection were compared with 45 healthy controls.Results: Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone (ACTH) was significantly increased in COVID-19 patients as compared to normal controls (p<0.001), but was dramatically decreased in critical cases as compared to non-critical patients (p=0.003).Conclusion: This study revealed a potential impact of SARS-CoV-2 infection on corticotroph cells and adenomas.

Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice (preprint)

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

The landscape of antibody binding to SARS-CoV-2 (preprint)

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), orf3a, and orf8 proteins are also humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved near-perfect diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that anti-SARS-CoV-2 antibodies appear to bind homologous peptide sequences in the 6 known human CoVs. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins, especially M, which should be considered in diagnostic, vaccine, and therapeutic development.

The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors (preprint)

A large number of hospitalized COVID-19 patients show neurological symptoms such as ischemic- and hemorrhagic stroke as well as encephalitis, and SARS-CoV-2 can directly infect endothelial cells leading to endotheliitis across multiple vascular beds. These findings suggest an involvement of the brain- and peripheral vasculature in COVID-19, but the underlying molecular mechanisms remain obscure. To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. We observed a distinct expression pattern of the cathepsins B (CTSB) and -L (CTSL) - which are able to substitute for the ACE2 co-receptor TMPRSS2 - in the human vasculature with CTSB being mainly expressed in the brain vasculature and CTSL predominantly in the peripheral vasculature, and these observations were confirmed at the protein level in the Human Protein Atlas and using immunofluorescence stainings. This expression pattern of SARS-CoV-2 viralentry associated proteases and SARS-CoV-2 interaction partners was also present in endothelial cells and microglia in the fetal brain, suggesting a developmentally establishedSARS-CoV-2 entry machinery in the human vasculature. At both the adult and fetal stages, we detected a distinct pattern of SARS-CoV-2 entry associated genes' transcripts in brain vascular endothelial cells and microglia, providing a potential explanation for an inflammatory response in the brain endothelium upon SARS-CoV-2 infection. Moreover, CTSB was co-expressed in adult and fetal brain endothelial cells with genes and pathways involved in innate immunity and inflammation, angiogenesis, blood-brain-barrier permeability, vascular metabolism, and coagulation, providing a potential explanation for the role of brain endothelial cells in clinically observed (neuro)vascular symptoms in COVID-19 patients. Our study serves as a publicly available single-cell atlas of SARS-CoV-2 related entry factors and interaction partners in human and mouse brain endothelial- and perivascular cells, which can be employed for future studies in clinical samples of COVID-19 patients.

Impact of the COVID-19 pandemic on mental health in pregnancy women: results from two cohort studies in China (preprint)

Background The COVID-19 pandemic led to a global atmosphere of anxiety and depression. However, the impact of this disaster on mental health in pregnancy women was not clear.Methods Based on two cohort study, the Novel Coronavirus Disease Influenced Pregnant Cohort Study (NCP) set up during the COVID-19 epidemic and the Healthy Baby Cohort Study (HBC) set up in 2012, we compared the anxiety, depression and stress levels of pregnant women who did not or did go through the COVID-19 pandemic and analyzed the risk factors for mental health in pregnancy women.Results There were 784 and 2448 participants in the CNP and HBC studies involved in the analysis, respectively. We found that there were 23.09% and 4.72% pregnant women suffering for mild and moderate-to-several anxieties for those in the NCP study, and 21.53% and 3.06% in the HBC study. The mild and moderate-to-several depression rate was 25.89% and 11.35% for those in the NCP study, and 19.81% and 0.51% for those in the HBC study, respectively. No significant difference was found for anxiety, depression and stress levels was found at each gestational trimester (p > 0.05). The pandemic of COVID-19 was significantly associated with maternal depression and stress (p < 0.05), with the co-efficient and 95%CI as 0.37 (0.18, 0.55) and − 0.12 (-0.09, -0.32), respectively. Pregnant women with pre-pregnancy obesity, higher educational level or good sleep quality might have lower risks for anxiety, depression and stress compared with the referenced groups.conclusions The pandemic had a huge impact on depression, especially moderate-to-sever level, in pregnant women at whatever gestational week; and that pre-pregnancy obesity, highly educated and sleep well ones had less anxiety and depression risks. The society, especially the family members, should pay more attention to pregnant ones and give more social support to them.