HIGHLIGHTSd Cross-sectional study of 44 hospitalized COVID-19 patients d RBD-specific IgG responses detectable in all patients 6 days after PCR confirmation d Neutralizing titers are detectable in all patients 6 days after PCR confirmation d RBD-specific IgG titers correlate with the neutralizing potency

28SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to 29 understand the dynamics, specificity, and neutralizing potency of the humoral immune response 30 during acute infection. Herein, we report the dynamics of antibody responses to the receptor-31 binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 32 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR 33 confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also 34 detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG 35 binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of 36 the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed 37 patients (n=231). These findings have important implications for our understanding of protective 38 immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of 39 much-needed vaccines. 40 41

Purpose Bone complications of metastatic disease, including skeletal-related events (SREs), impair patients' functioning and quality of life. In a randomized, phase 3 trial of 1,776 patients with metastases from solid tumors (except breast or prostate) or multiple myeloma, denosumab was non-inferior to zoledronic acid (ZA) in delaying or preventing SREs. This ad hoc analysis reports outcomes in the subgroup of 1,597 patients with solid tumors, excluding patients with multiple myeloma. Methods Patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg, adjusted for creatinine clearance, with calcium and vitamin D supplementation recommended. Endpoints included times to first on-study SRE, first-and-subsequent SREs, and pain worsening. Results Denosumab significantly delayed time to first onstudy SRE compared with ZA (HR, 0.81; 95 % CI, 0.68-0.96) and time to first-and-subsequent SREs (RR, 0.85; 95 % CI, 0.72-1.00). Denosumab also significantly delayed time to development of moderate or severe pain (HR, 0.81; 95 % CI, 0.66-1.00), pain worsening (HR, 0.83; 95 % CI, 0.71-0.97), and worsening pain interference in patients with no/mild baseline pain (HR, 0.77; 95 % CI, 0.61-0.96). Adverse event rates were 96 % in both groups. Grade 3 or 4 hypocalcemia, mostly without clinical sequelae, was more frequent in denosumab-treated patients (denosumab 4 %, ZA 2 %). Osteonecrosis of the jaw occurred infrequently (denosumab 0.8 %, ZA 1.1 %). Conclusions Denosumab was more effective in delaying or preventing SREs in patients with bone metastases from solid tumors and also prevented pain progression compared to ZA in this ad hoc analysis.

We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated !500Â coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at !5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n Z 27), deletions (n Z 5), insertions (n Z 3), and multinucleotide variants (n Z 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/ 80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. (J Mol Diagn 2016, 18: 299e315; http:// dx

Reference information: JCI Insight. 2017;2(5):e90487. https://