SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City. We also show that titers are relatively stable for at least a period approximating 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Preexisting lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a variety of cancers. Recent studies also suggest that lymphocytic responses may identify patients more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic efficacy of immune checkpoint blockade can be enhanced through strategies that induce tumor inflammation. To achieve this effect, here we explored the immunotherapeutic potential of oncolytic Newcastle Disease Virus (NDV). We find that localized intratumoral therapy of B16 melanoma with NDV induces inflammatory responses leading to lymphocytic infiltrates and anti-tumor effect in distant (non-virally injected) tumors without distant virus spread. The inflammatory effect coincided with distant tumor infiltration with tumor-specific CD4+ and CD8+ T cells, which was dependent on the identity of the virus-injected tumor. Combination therapy with localized NDV and systemic CTLA-4 blockade led to rejection of pre-established distant tumors and protection from tumor re-challenge in poorly-immunogenic tumor models, irrespective of tumor cell line sensitivity to NDV-mediated lysis. Therapeutic effect was associated with marked distant tumor infiltration with activated CD8+ and CD4+ effector but not regulatory T cells, and was dependent on CD8+ cells, NK cells and type I interferon. Our findings demonstrate that localized therapy with oncolytic NDV induces inflammatory immune infiltrates in distant tumors, making them susceptible to systemic therapy with immunomodulatory antibodies, which provides a strong rationale for investigation of such combination therapies in clinic.

To explore the basis of metastasis, we compared the human breast cancer lines MCF-7 and MDA-MB453, which have low invasive ability, with their sublines MCF7-I4 and MDA-MB453-I4 with high invasive ability for gene expression and signaling pathways. We previously showed that the I4 lines had dramatically elevated levels of Twist compared with their parental lines. In this study, we observed significantly increased STAT3 Twist, a highly conserved basic helix-loop-helix transcriptional factor, was previously shown to play a pivotal role in mesodermal, myoblast, and osteoblast differentiation (1-3).Mutational inactivation of the Twist gene resulted in SaethreChotzen syndrome, an autosomal dominant disorder characterized by premature fusion of the cranial sutures, skull deformations, limb abnormalities, and facial dysmorphisims (4). Recent studies have demonstrated that Twist also played a key role in the development and progression of human cancer (5).Twist is frequently overexpressed in human rhabdomyosarcoma, gastric carcinoma, melanoma, breast cancer, prostate cancer, liver carcinoma, and glioma (5). The elevated Twist protein levels are associated with advanced tumor stage and poor prognosis in several types of cancer (6 -8). Further, increased Twist in cancer cells has been shown to promote metastatic ability in vivo and induce epithelial to mesenchymal transition, cell survival, angiogenesis, and chemoresistance in vitro (9 -14). In addition, ectopic expression of Twist in mouse embryonic fibroblasts promotes soft agar colony formation, indicating its role in malignant transformation (10). A number of downstream target genes of Twist have been identified and shown to mediate its function (10). Previous studies have demonstrated that epithelial to mesenchymal transition-associated molecules, such as E-cadherin and N-cadherin, are tightly regulated by Twist (9, 15). We have recently shown that AKT signaling is promoted by Twist through transcriptional up-regulation of AKT2 (16). However, the molecular mechanism for the up-regulation of Twist in cancer cells is less clear.Signal transducer and activator of transcription 3 (STAT3) 4 protein is a member of a family of latent cytoplasmic transcriptional factors that convey signals from the cell surface to the nucleus upon activation by cytokines and growth factors (17). Engagement of cell surface receptors by polypeptide ligands induces tyrosine phosphorylation of STAT3 protein by Janus kinases, growth factor receptor tyrosine kinases, and, in some cases, Src family tyrosine kinases. The phospho-STAT3 protein dimerizes and translocates to nucleus to regulate expression of the genes harboring STAT3-binding sites in their promoters (18). STAT3 has been shown to regulate genes that control fundamental biological processes including cell proliferation, survival, and development (18). Activated STAT3 was able to transform cells in vitro (19) and is required for cell transformation of a number of oncogenes (12,19,20). Numerous studies * This work was supported, in whole or...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. Methods In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. Findings Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. Interpretation Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. Funding None.

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.

2Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a 1 3 CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

Newcastle disease virus (NDV) is a negative-sense RNA virus that has been shown to possess oncolytic activity. NDV's selective replication in tumor cells has been previously suggested to be due to the lack of a proper antiviral response in these cells. Here we demonstrate that NDV possesses oncolytic activity in tumor cells capable of a robust type I interferon (IFN) response, suggesting that another mechanism underlies NDV's tumor specificity. We show that the oncolytic selectivity of NDV for tumor cells is dependent upon tumor cell resistance to apoptosis. Utilizing the human non-small-cell lung cancer cell line A549 overexpressing the antiapoptotic protein Bcl-xL, we show significant enhancement of oncolytic activity and NDV replication. Interestingly, while the Bcl-xL-overexpressing cells were resistant to apoptotic stimuli induced by chemotherapeutic agents and early viral replication, during the subsequent viral cycles, we observed a paradoxical increase in apoptosis in response to NDV. The increased oncolytic activity seen was secondary to enhanced viral replication and syncytium formation. The induction of a type I IFN response was enhanced in Bcl-xL cells. Overall, these findings propose a new mechanism for cancer cell specificity for NDV, making it an attractive anticancer agent for chemoresistant tumors with enhanced antiapoptotic activity.

Patients in the present sample appear motivated for surgery primarily to control current medical problems. However, a significant portion of patients do endorse psychological and quality of life factors as important in their decision to seek weight loss surgery.