IMMUNOGENICITY OF SARS-CoV-2 mRNA VACCINATION IN IDIOPATHIC CD4 LYMPHOPENIA

Background: The rapid development of SARS-CoV-2 mRNA vaccines has been a remarkable success of the COVID-19 pandemic, but vaccine-induced immunity is heterogeneous in immunocompromised populations. We sought to determine the immunogenicity of SARS-CoV-2 mRNA vaccines in a cohort of people with idiopathic CD4 lymphopenia (ICL). Method(s): 25-patients with ICL followed at the National Institutes of Health on a natural history protocol were evaluated between 2020-2022. Blood and serum was collected within 4-12 weeks after their second and/or third SARS-CoV-2 mRNA vaccine dose. Twenty-three matched healthy volunteers (HVs) provided blood samples at similar timepoints post-mRNA vaccination on a separate clinical protocol. Pre-vaccine blood samples were also used when available. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell stimulation assays were performed to quantify SARS-CoV-2 specific T-cell responses. Comparisons were made with Wilcoxon test. Result(s): Twenty-participants with ICL had samples collected after their second mRNA vaccine and 7-individuals after the third dose. Median age at vaccination was 51-years (IQR: 44-62) and 12 were women (48%). Median CD4 T-cell count was 150 cells/muL (IQR: 85-188) at the time of vaccination, and 11-individuals (44%) had a baseline CD4 count <=100 cells/muL. HVs had a median age of 54-years (IQR: 43-60) with 13-women (56.5%). Anti-spike IgG antibody levels were significantly greater in HVs than those with ICL after 2-doses. Lower SARS-CoV-2 IgG antibody production was primarily observed in those with baseline CD4 T-cells <=100 cells/mul (Figure-1A). The decreased production in ICL remained after a third vaccine dose (Figure-1B). There was a significant correlation between anti-spike IgG and baseline CD4 count. Spike-specific CD4 T-cell responses in volunteers compared to those with ICL demonstrated similar levels of activation induced markers (CD154+CD69+) and cytokine production (IFNgamma+, TNFalpha+, IL2+) after two or three mRNA vaccine doses. Quantitatively the smallest responses were observed in those with lower baseline CD4 T-cells (Figure 1C-D). Minimal SARS-CoV-2 CD8 T-cell responses were detected in both groups. Conclusion(s): Patients with ICL and baseline CD4 T-cells >100 mount similar humoral and cellular immune responses to SARS-CoV-2 vaccination as healthy volunteers. Those with baseline CD4 T-cells <=100 have impaired vaccine- induced immunity and should be prioritized to additional boosters and continue other risk mitigation strategies. (Figure Presented).

Africa's Development Debts

Public debt levels in sub-Saharan Africa rose sharply in the wake of the global financial crisis, and a number of countries are now classified by the World Bank and International Monetary Fund as at high risk of debt distress. By contrast with the debt crisis of the 1980s and 1990s, however, concerns were not region wide as recently as early 2020, and the policy environment for growth remains robust for the majority of countries in the region. The external environment nonetheless poses a set of region-wide risks that include the economic effects of the COVID-19 pandemic and are exacerbated by the increase in market-based debt and the retreat of the Paris Club among official creditors. Changes in perceived creditworthiness can now drive distress, and new challenges of creditor coordination will complicate the debt restructuring process. We motivate a research agenda that focuses on development assets at risk as rising debt service obligations crowd out development as well as operational and maintenance budgets. Preserving and enhancing these assets, which include advances in human capital and infrastructure and an improved investment environment, should be a central objective of domestic policy actions, preventative debt restructurings and institutional approaches to debt distress. © 2021 The Author(s). Published by Oxford University Press on behalf of the Centre for the Study of African Economies.

Reykjanes Mantle Convection and Climate: Crustal Objectives

The five primary sites proposed for International Ocean Discovery Program (IODP) Expedition 395, which was postponed because of the COVID-19 pandemic, were cored during IODP Expedition 395C. The Expedition 395C operations, shipboard measurements, and sampling were adjusted to account for the absence of a sailing science party. The Expedition 395/395C objectives are (1) to investigate temporal variations in ocean crust generation at the Reykjanes Ridge and test hypotheses for the influence of Iceland mantle plume fluctuations on these processes, (2) to analyze sedimentation rates at the Björn and Gardar contourite drifts, as proxies for Cenozoic variations of North Atlantic deepwater circulation, and for uplift and subsidence of the Greenland-Scotland Ridge gateway related to plume activity, and (3) to analyze the alteration of oceanic crust and its interaction with seawater and sediments. During Expedition 395C, basalt cores were collected at four sites: U1554, U1555, U1562, and U1563. Sediment cores were also collected from these sites as well as from Site U1564, and casing was installed to 602 m at Site U1554. The amount of recovered cores, their preliminary descriptions, and the analyses of shipboard samples show that the results of Expedition 395C will fulfill a significant part of the Expedition 395 objectives. Basalts were collected from two V-shaped ridge and trough pairs, which will allow the investigation of the variability in mantle source and temperature causing this ridge/trough pattern. Basalt cores span an expected age range of 2.8–13.9 Ma, which will allow us to investigate the hydrothermal weathering processes. Sediments from the Björn drift were cored to basement, along with the uppermost 600 m of sediments from the Gardar drift. The data provided by Expedition 395C are a major advancement in achieving the work of Expedition 395. © 2022 Authors. All rights reserved.

TGF-Β2 IS ASSOCIATED with ASYMPTOMATIC/MILD SARS-CoV-2 INFECTION during PREGNANCY

Background: COVID-19 has been a devastating disease and a major public health concern mainly to susceptible populations. Methods: We accessed two groups of pregnant women at the time of delivery: SARS-CoV2 active infection and convalescents. To investigate the factors contributing to COVID19 severity we have assessed several immunological parameters including cytokines/chemokine levels in the maternal and cord blood plasma. We have evaluated 33 cytokines. Our findings were validated in vitro in HTBE (Human tracheobronchial epithelial) cells infected with live SARS-COV2 (wild type). Results: Our cohort was enriched in high-risk subjects, including African American and obese women. Only 6% had severe or critical disease, contrasting with the 20-25% reported in some pregnant cohorts. TGFb2 levels were significantly associated with asymptomatic/mild disease in both active and convalescent cohorts, and inversely correlated with IP10, IL6 and IL8, known to be part of the cytokine storm post-infection. Pre-treatment of HTBE with TGFb2 for 48 hours led to a significant decay in viral loads at 72h post-infection. This control was associated with significantly higher IL-6 (IFNb2) levels prior to infection, and significantly higher expression of anti-viral genes at 72h pi (MX1, IFNA1, IFNA2, IFNL1, STAT1). Additionally, TGFb2 pre-treatment suppressed the expression of the cytokines IP-10, IL1b and IL8. Conclusion: Altogether this data suggested that TGFB2 plays a protective role in SARS-COV2 infection in this high-risk population by improving epithelial cells intrinsic antiviral function and by modulating the expression of the cytokines associated to the heightened inflammation in severe cases.

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial

[Figure: see text].