Objective To characterize the demographic and clinical features of pediatric SARS-CoV-2 syndromes and identify admission variables predictive of disease severity. Study design We conducted a multicenter, retrospective and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at eight sites in New York, New Jersey, and Connecticut. Results We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into three groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% versus 18%, P =.02). Seven patients (2%) died and 114 (41%) were admitted to the ICU. In multivariable analyses, obesity (OR=3.39, 95% CI:1.26-9.10, P =.02) and hypoxia on admission (OR=4.01; 95% CI:1.14-14.15; P =.03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR=8.33 per unit decrease in 10 9 cells/L, 95% CI:2.32-33.33, P =.001) and higher C-reactive protein (OR=1.06 per unit increase in mg/dL, 95% CI:1.01-1.12, P =.017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. Conclusions We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Background The gD/AS04 vaccine failed to prevent HSV-2 in clinical trials. Failure was recapitulated in mice where the vaccine elicited neutralizing but not antibody-dependent cell-mediated cytotoxicity (ADCC) responses. Preclinical findings suggest that ADCC is important for protection but there is limited clinical data. We hypothesized that gD/AS04 and acute HSV-2 infection elicit primarily neutralizing antibodies whereas ADCC emerges over time. Methods HSV-specific IgG, subclass, function (neutralization, C1q binding and ADCC), and antigenic targets were compared (paired t-test or Mann-Whitney) at enrollment and following gD/AS04 vaccination, before and after HSV-2 acquisition in vaccine controls, and in an independent cohort of chronic HSV-2 infection. Results Vaccination elicited only a neutralizing response whereas acute infection elicited neutralizing and C1q-binding antibodies but not a significant ADCC response. Antibodies to gD were exclusively IgG1 and only neutralizing. In contrast, women with chronic HSV-2 infection had significantly greater ADCC responses and targeted a broader range of viral antigens compared to acutely-infected or gD/AS04 vaccine recipients (p< 0.001). Conclusions Results from gD/AS04 vaccinated or acutely infected women recapitulate murine findings of limited functional antibody responses, supporting the speculation that vaccines that generate polyfunctional and specifically ADCC responses may be required to prevent HSV-2 acquisition and limit recurrences.

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