Impaired potency of neutralizing antibodies against cell-cell fusion mediated by SARS-CoV-2.

The SARS-CoV-2 Omicron subvariants have dominated the pandemic due to their high transmissibility and immune evasion conferred by the spike mutations. The Omicron subvariants can spread by cell-free virus infection and cell-cell fusion, the latter of which is more effective but has not been extensively investigated. In this study, we developed a simple and high-throughput assay that provides a rapid readout to quantify cell-cell fusion mediated by the SARS-CoV-2 spike proteins without using live or pseudotyped virus. This assay can be used to identify variants of concern and to screen for prophylactic and therapeutic agents. We further evaluated a panel of monoclonal antibodies (mAbs) and vaccinee sera against D614G and Omicron subvariants, finding that cell-cell fusion is substantially more resistant to mAb and serum inhibition than cell-free virus infection. Such results have important implications for the development of vaccines and antiviral antibody drugs against cell-cell fusion induced by SARS-CoV-2 spikes.

Detection of pancreatic cancer with two- and three-dimensional radiomic analysis in a nationwide population-based real-world dataset.

BACKGROUND: CT is the major detection tool for pancreatic cancer (PC). However, approximately 40% of PCs < 2 cm are missed on CT, underscoring a pressing need for tools to supplement radiologist interpretation. METHODS: Contrast-enhanced CT studies of 546 patients with pancreatic adenocarcinoma diagnosed by histology/cytology between January 2005 and December 2019 and 733 CT studies of controls with normal pancreas obtained between the same period in a tertiary referral center were retrospectively collected for developing an automatic end-to-end computer-aided detection (CAD) tool for PC using two-dimensional (2D) and three-dimensional (3D) radiomic analysis with machine learning. The CAD tool was tested in a nationwide dataset comprising 1,477 CT studies (671 PCs, 806 controls) obtained from institutions throughout Taiwan. RESULTS: The CAD tool achieved 0.918 (95% CI, 0.895-0.938) sensitivity and 0.822 (95% CI, 0.794-0.848) specificity in differentiating between studies with and without PC (area under curve 0.947, 95% CI, 0.936-0.958), with 0.707 (95% CI, 0.602-0.797) sensitivity for tumors < 2 cm. The positive and negative likelihood ratios of PC were 5.17 (95% CI, 4.45-6.01) and 0.10 (95% CI, 0.08-0.13), respectively. Where high specificity is needed, using 2D and 3D analyses in series yielded 0.952 (95% CI, 0.934-0.965) specificity with a sensitivity of 0.742 (95% CI, 0.707-0.775), whereas using 2D and 3D analyses in parallel to maximize sensitivity yielded 0.915 (95% CI, 0.891-0.935) sensitivity at a specificity of 0.791 (95% CI, 0.762-0.819). CONCLUSIONS: The high accuracy and robustness of the CAD tool supported its potential for enhancing the detection of PC.

Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.