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The association of mortality with the early humoral response to SARS-CoV-2 infection within the first few days after onset of symptoms (DAOS) has not been thoroughly investigated partly due to a lack of sufficiently sensitive antibody testing methods. Here we report two sensitive and automated testing-on-a-probe (TOP) biosensor assays for SARS-CoV-2 viral specific total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), which are suitable for clinical use. The TOP assays employ an RBD-coated quartz probe using a Cy5-Streptavidin-polysacharide conjugate to improve sensitivity and minimize interference. Disposable cartridges containing pre-dispensed reagents require no liquid manipulation or fluidics during testing. The TOP-TAb assay exhibited higher sensitivity in the 0-7 DAOS window than a widely used FDA-EUA assay. The rapid and automated TOP-SNAb correlated well with two well-established SARS-CoV-2 virus neutralization tests. The clinical utility of the TOP assays was demonstrated by evaluating early antibody responses in 120 SARS-CoV-2 RT-PCR positive adult hospitalized patients. Higher TAb and SNAb positivity rates and more robust antibody responses at patient's initial hospital presentation were seen in inpatients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who had negative TAb and/or SNAb at initial hospital presentation were at a higher risk of in-hospital mortality. Furthermore, TAb and SNAb levels at presentation were inversely associated with SARS-CoV-2 viral load based on concurrent RT-PCR testing. Overall, the sensitive and automated TAb and SNAb assays allow the detection of early SARS-CoV-2 antibodies which associate with mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults., Objective: To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses., Design, Setting, and Participants: This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years., Main Outcomes and Measures: SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years)., Results: Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant., Conclusions and Relevance: The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.

Human T-cell lymphotropic virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATLL) occurs endemically in southwestern Japan, the Caribbean, and West Africa, but occurs sporadically in most of the rest of the world. However, because ATLL and non-HTLV-I associated T-cell neoplasms share overlapping clinicopathologic features, the prevalence of ATLL in nonendemic regions is unknown. In this study, 75 T-cell neoplasms randomly procured from the metropolitan New York City area were examined by polymerase chain reaction (PCR) for the presence of integrated HTLV-I proviral sequences. HTLV-I genomic sequences were detected by PCR in 6 of the 75 cases (8%); this result was confirmed by Southern blot hybridization. The clinicopathologic features of the HTLV-I positive and HTLV-I negative T-cell neoplasms were then compared. Although the clinicopathologic features of patients from these two groups overlapped, some findings were more commonly associated with HTLV-I positive neoplasms. Five of the six patients with HTLV-I positive neoplasms were from HTLV-I endemic areas, five were black, five were women, and five were less than 45 years of age, while the majority of the patients with HTLV-I negative T-cell malignancies were elderly white men. The incidence of hypercalcemia and lytic bone lesions was significantly more common among patients with HTLV-I positive T-cell neoplasms (P less than .001 and P = .004, respectively). The immunophenotypes of the HTLV-I positive and negative tumors were similar; however, all HTLV-I positive neoplasms were CD7 negative (P less than .001). In summary, our findings: (1) demonstrate the special clinicopathologic and immunophenotypic features of HTLV-I positive T-cell neoplasms, (2) suggest that most of the rare cases of HTLV-I-associated T-cell neoplasms occurring in HTLV-I nonendemic areas are actually endemic cases; and (3) that PCR is a sensitive, clinically useful technique for identifying HTLV-I associated T-cell neoplasms.