ABSTRACT
INTRODUCTION: Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant proinflammatory response and a spectrum of clinical presentations after central nervous system infection. METHOD(S): Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls. RESULT(S): We demonstrate that patient-derivedGBMtissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells: M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARSCoV- 2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05). CONCLUSION(S): GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARSCoV- 2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.
ABSTRACT
Aims The aim of this study was to provide an early interval evaluation of laboratory characteristics and clinical outcomes of adult patients with qRT-PCR-confirmed SARS-CoV-2 infection. Methods We performed a single-centre retrospective cohort study. All patients with qRT-PCR-confirmed SARS-CoV-2 infection admitted from March 6th to April 2nd were included. Daily laboratory, radiological and clinical parameters were manually collected on every patient. Results Forty-six patients were included in the analysis. Thirty-three (72%) of patients were male. The majority of patients (n=33, 89%) had at least one baseline comorbidity. Bilateral consolidation on chest x-ray (n=24, 52%) correlated with level of respiratory support required but not with mortality. Documented fever (n=33, 48%) and hypotension (n=4, 9%) correlated with highest level of respiratory support required. Older age, obesity and more than one baseline comorbid condition were associated with mortality. Regarding laboratory markers, degree of neutrophilia, lymphopenia (n=33, 73%) and raised CRP were significantly associated with death. Raised LDH, ferritin and D-dimer concentrations correlated with degree of oxygen requirement. There was no association between an early PCR cycle quantification (Cq) value (used as a proxy for viral load) and patient outcome. Conclusions We found multiple characteristics that correlated with outcome. These findings give an indication as to those patients that are at risk of a poor clinical outcome. © 2020, Irish Medical Association. All rights reserved.