Regulatory role of endoplasmic reticulum resident chaperone protein ERp29 in anti-murine ß-coronavirus host cell response.

Gap junctional intercellular communication (GJIC) involving astrocytes is important for proper CNS homeostasis. As determined in our previous studies, trafficking of the predominant astrocyte GJ protein, Connexin43 (Cx43), is disrupted in response to infection with a neurotropic murine ß-coronavirus (MHV-A59). However, how host factors are involved in Cx43 trafficking and the infection response is not clear. Here, we show that Cx43 retention due to MHV-A59 infection was associated with increased ER stress and reduced expression of chaperone protein ERp29. Treatment of MHV-A59-infected astrocytes with the chemical chaperone 4-sodium phenylbutyrate increased ERp29 expression, rescued Cx43 transport to the cell surface, increased GJIC, and reduced ER stress. We obtained similar results using an astrocytoma cell line (delayed brain tumor) upon MHV-A59 infection. Critically, delayed brain tumor cells transfected to express exogenous ERp29 were less susceptible to MHV-A59 infection and showed increased Cx43-mediated GJIC. Treatment with Cx43 mimetic peptides inhibited GJIC and increased viral susceptibility, demonstrating a role for intercellular communication in reducing MHV-A59 infectivity. Taken together, these results support a therapeutically targetable ERp29-dependent mechanism where ß-coronavirus infectivity is modulated by reducing ER stress and rescuing Cx43 trafficking and function.

Impact of the COVID-19 pandemic on neuro-oncology outcomes.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even "elective" neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic and investigates patient outcomes in 2020 compared to a historical control. METHODS: We performed a retrospective review of patients with malignant brain tumor diagnoses who were seen at our institution between March 13 and May 1 of 2020 and 2019. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. RESULTS: 112 patients from 2020 to 166 patients from 2019 were included. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p = 0.0160) and use of telehealth (p < 0.0001) in 2020. Patients in 2020 who utilized telehealth visits had significantly more stable tumor control than those who had office visits (p = 0.0124), consistent with appropriate use of in-person visits for patients with progression. CONCLUSIONS: Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes were successful and may inform management during the ongoing pandemic, especially with the emergence of the Delta variant.

Evidence for residual SARS-CoV-2 in glioblastoma tissue of a convalescent patient.

Since coronavirus disease 2019 (COVID-19) swept all over the world, several studies have shown the susceptibility of a patient with cancer to COVID-19. In this case, the removed glioblastoma multiforme (GBM)-adjacent (GBM-A), GBM-peritumor and GBM-central (GBM-C) tissues from a convalescent patient of COVID-19, who also suffered from glioblastoma meanwhile, together with GBM-A and GBM tissues from a patient without COVID-19 history as negative controls, were used for RNA ISH, electron microscopy observing and immunohistochemical staining of ACE2 and the virus antigen (N protein). The results of RNA ISH, electron microscopy observing showed that SARS-CoV-2 directly infects some cells within human GBM tissues and SARS-CoV-2 in GBM-C tissue still exists even when it is cleared elsewhere. Immunohistochemical staining of ACE2 and N protein showed that the expressions of ACE2 are significantly higher in specimens, including GBM-C tissue from COVID-19 patient than other types of tissue. The unique phenomenon suggests that the surgical protection level should be upgraded even if the patient is in a convalescent period and the pharyngeal swab tests show negative results. Furthermore, more attention should be paid to confirm whether the shelter-like phenomenon happens in other malignancies due to the similar microenvironment and high expression of ACE2 in some malignancies.

Neurosurgical management of brain and spine tumors in the COVID-19 era: an institutional experience from the epicenter of the pandemic.

The challenges of neurosurgical patient management and surgical decision-making during the 2019-2020 COVID-19 worldwide pandemic are immense and never-before-seen in our generation of neurosurgeons. In this case-based formatted report, we present the Mount Sinai Hospital (New York, NY) Department of Neurosurgery institutional experience in the epicenter of the pandemic and the guiding principles for our current management of intracranial, skull base, and spine tumors. The detailed explanations of our surgical reasoning for each tumor case is tailored to assist neurosurgeons across the United States as they face these complex operative decisions put forth by the realities of the pandemic.

Inpatient and outpatient case prioritization for patients with neuro-oncologic disease amid the COVID-19 pandemic: general guidance for neuro-oncology practitioners from the AANS/CNS Tumor Section and Society for Neuro-Oncology.

The Coronavirus pandemic has created unprecedented strain on medical resources at health care institutions around the world. At many institutions, this has resulted in efforts to prioritize cases with an attempt to balance the acuity of medical needs with available resources. Here, we provide a framework for institutions and governments to help adjudicate treatment allocations to patients with neuro-oncologic disease.