Evaluation of Cellular and Serological Responses to Acute SARS-CoV-2 Infection Demonstrates the Functional Importance of the Receptor-Binding Domain.

The factors that control the development of an effective immune response to the recently emerged SARS-CoV-2 virus are poorly understood. In this study, we provide a cross-sectional analysis of the dynamics of B cell responses to SARS-CoV-2 infection in hospitalized COVID-19 patients. We observe changes in B cell subsets consistent with a robust humoral immune response, including significant expansion of plasmablasts and activated receptor-binding domain (RBD)-specific memory B cell populations. We observe elevated titers of Abs to SARS-CoV-2 RBD, full-length Spike, and nucleoprotein over the course of infection, with higher levels of RBD-specific IgG correlating with increased serum neutralization. Depletion of RBD-specific Abs from serum removed a major portion of neutralizing activity in most individuals. Some donors did retain significant residual neutralization activity, suggesting a potential Ab subset targeting non-RBD epitopes. Taken together, these findings are instructive for future vaccine design and mAb strategies.

First-in-Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID-19.

Therapeutics for patients hospitalized with coronavirus disease 2019 (COVID-19) are urgently needed during the pandemic. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. J2W-MC-PYAA was a randomized, double-blind, sponsor unblinded, placebo-controlled, single ascending dose first-in-human trial (NCT04411628) in hospitalized patients with COVID-19. A total of 24 patients received either placebo or a single dose of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg). The primary objective was assessment of safety and tolerability, including adverse events and serious adverse events, with secondary objectives of pharmacokinetic (PK) and pharmacodynamic analyses. Treatment-emergent adverse event (TEAE) rates were identical in the placebo and pooled bamlanivimab groups (66.7%). There were no apparent dose-related increases in the number or severity of TEAEs. There were no serious adverse events or deaths during the study, and no discontinuations due to adverse events. PKs of bamlanivimab is linear and exposure increased proportionally with dose following single i.v. administration. The half-life was ~ 17 days. These results demonstrate the favorable safety profile of bamlanivimab, and provided the initial critical evaluation of safety, tolerability, and PKs in support of the development of bamlanivimab in several ongoing clinical trials.

The burden of anaemia among displaced women and children in refugee settings worldwide, 2013-2016.

INTRODUCTION: Displaced persons have a unique risk for developing anaemia due to often limited diets, overcrowding, new infections and inadequate sanitation and hygiene. The lack of anaemia prevalence estimates among the displaced inhibit global planning for anaemia reduction. METHODS: We analysed population representative, cross-sectional nutrition surveys from 2013 to 2016 conducted by the United Nations High Commissioner for Refugees and partner agencies. Included surveys measured haemoglobin concentration among children 6-59 months, non-pregnant women 15-49 years, or both groups. For each survey, we calculated mean haemoglobin and prevalence of total anaemia (<110 g/L in children, <120 g/L in women), and classified public health severity following WHO guidelines. Pearson correlations between indicators from women and children surveys were calculated where both subpopulations were measured. RESULTS: Analysis included 196 surveys among children and 184 surveys among women from 121 unique refugee settings in 24 countries. The median prevalence of total anaemia in children and women was 44% and 28%, respectively. Sixty-one per cent of child surveys indicated a problem of severe public health importance compared with 25% of surveys in women. The prevalence of total anaemia in children and women was strongly correlated (ρ=0.80). Median prevalence of total anaemia was approximately 55% greater and mean haemoglobin was 6 g/L lower among children age 6-23 months compared with children 24-59 months. West and Central Africa region had the highest median prevalence of anaemia both in women and children. CONCLUSION: While the burden of anaemia is high among the displaced, it mirrors that of the general population. Haemoglobin should continue to be measured in nutrition surveys in refugee settings. Sustained, multisectoral efforts to reduce anaemia are needed, with specific focus on children under 2 years of age and refugee settings in the West and Central Africa region.