Comparison of platelet-and endothelial-associated biomarkers of disease activity in people hospitalized with Covid-19 with and without HIV co-infection

INTRODUCTION : SARS-CoV-2 elicits a hyper-inflammatory response that contributes to increased morbidity and mortality in patients with COVID-19. In the case of HIV infection, despite effective anti-retroviral therapy, people living with HIV (PLWH) experience chronic systemic immune activation, which renders them particularly vulnerable to the life-threatening pulmonary, cardiovascular and other complications of SARS-CoV-2 co-infection. The focus of the study was a comparison of the concentrations of systemic indicators o\f innate immune dysfunction in SARS-CoV-2-PCR-positive patients (n=174) admitted with COVID-19, 37 of whom were co-infected with HIV. METHODS : Participants were recruited from May 2020 to November 2021. Biomarkers included platelet-associated cytokines, chemokines, and growth factors (IL-1b, IL-6, IL-8, MIP-1a, RANTES, PDGF-BB, TGF-b1 and TNF-a) and endothelial associated markers (IL-1b, IL-1Ra, ICAM-1 and VEGF). RESULTS : PLWH were significantly younger (p=0.002) and more likely to be female (p=0.001); median CD4+ T-cell count was 256 (IQR 115 -388) cells/mL and the median HIV viral load (VL) was 20 (IQR 20 -12,980) copies/mL. Fractional inspired oxygen (FiO2) was high in both groups, but higher in patients without HIV infection (p=0.0165), reflecting a greater need for oxygen supplementation. With the exception of PDGF-BB, the levels of all the biomarkers of innate immune activation were increased in SARS-CoV-2/HIV-co-infected and SARSCoV- 2/HIV-uninfected sub-groups relative to those of a control group of healthy participants. The magnitudes of the increases in the levels of these biomarkers were comparable between the SARS-CoV-2 -infected sub-groups, the one exception being RANTES, which was significantly higher in the subgroup without HIV. After adjusting for age, sex, and diabetes in the multivariable model, only the association between HIV status and VEGF was statistically significant (p=0.034). VEGF was significantly higher in PLWH with a CD4+ Tcell count >200 cells/mL (p=0.040) and those with a suppressed VL (p=0.0077). DISCUSSION : These findings suggest that HIV co-infection is not associated with increased intensity of the systemic innate inflammatory response during SARSCoV- 2 co-infection, which may underpin the equivalent durations of hospital stay, outcome and mortality rates in the SARS-CoV-2/HIV-infected and -uninfected sub-groups investigated in the current study. The apparent association of increased levels of plasma VEGF with SARS-CoV-2/HIV coinfection does, however, merit further investigation.http://www.frontiersin.org/Immunologyam2024ImmunologyInternal MedicineSDG-03:Good heatlh and well-bein

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence

DATA AVAILABILITY : Complete individual patient data and the analysis code in R are available to researchers on reasonable request from the corresponding author, M.T.B.BACKGROUND : HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. OBJECTIVES : We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. METHOD : We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). RESULTS : The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people; most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range: 66–397) cells/μL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio = 1.1, 95% confidence interval: 0.6–2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. CONCLUSION : PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL.http://www.sajhivmed.org.zaam2024ImmunologyInternal MedicineSDG-03:Good heatlh and well-bein

Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus variants

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta, or Delta variants, we showed that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta Plus (Delta+), which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting that the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+, and Omicron, which all possess the N417 residue. We isolated an N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D MAb utilized the IGHV3-23*01 germ line gene and had somatic hypermutations similar to those of previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targeting escape mutations, such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines. IMPORTANCE : The evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring various immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants and to define shared epitopes. We show that Beta and Delta infections resulted in antibody responses that were more cross-reactive than the original D614G variant, but they had differing patterns of cross-reactivity. We further isolated an antibody from Beta infection which targeted the N417 site, enabling cross-neutralization of Beta, Delta+, and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.The South African Research Chairs Initiative of the Department of Science and Innovation, the National Research Foundation of South Africa, the SA Medical Research Council SHIP program and the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program.https://journals.asm.org/journal/jvihj2023ImmunologyInternal Medicin

Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent sera regardless of infecting variant

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4 and BA.5 variants caused major waves of infections. Here, we assess the sensitivity of BA.4 to binding, neutralization, and antibodydependent cellular cytotoxicity (ADCC) potential, measured by FcgRIIIa signaling, in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high-level neutralization resistance regardless of the infecting variant. However, BTIs retain activity against BA.4, albeit at reduced titers. BA.4 sensitivity to ADCC is reduced compared with other variants but with smaller fold losses compared with neutralization and similar patterns of cross-reactivity. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infection, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC potential against BA.4 is reduced, residual activity may contribute to observed protection from severe disease.The South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa, the South African Medical Research Council SHIP program, the European Union-Africa Concerted Action on SAR-CoV-2 Virus Variant and Immunological Surveillance (CoVICIS) consortium, and the Centre for the AIDS Programme of Research in South Africa (CAPRISA), the Bill and Melinda Gates Foundation through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program.https://www.cell.com/cell-reports-medicine/homeam2024ImmunologyInternal MedicineSDG-03:Good heatlh and well-bein

SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals

The SARS-CoV-2 Omicron variant escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers cross-reactive humoral responses to other variants of concern (VOCs) remains unknown. We used plasma from 20 unvaccinated and 7 vaccinated individuals infected by Omicron BA.1 to test binding, Fc effector function, and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies targeted Omicron and other VOCs at comparable levels. However, Omicron BA.1- triggered neutralization was not extensively cross-reactive for VOCs (14- to 31-fold titer reduction), and we observed 4-fold decreased titers against Omicron BA.2. In contrast, vaccination followed by breakthrough Omicron infection associated with improved cross-neutralization of VOCs with titers exceeding 1:2,100. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Although Omicron-based immunogens might be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2-naive individuals.The South African Research Chairs Initiative of the Department of Science and Innovation, the National Research Foundation of South Africa, the South African Medical Research Council Strategic Health Innovation Partnerships (SHIP) program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA), the Bill and Melinda Gates Foundation through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program and L’Oreal/UNESCO Women in Science South Africa Young Talents award.http://www.cell.com/cell-host-microbe/homeam2023ImmunologyMedical Virolog

Analysis of choral works by the Zulu composer : Professor R.T. Caluza

No abstract availableMini Dissertation (BA (Music))--University of Pretoria, 1967.MusicBA (Music)Unrestricte

Grade R teachers’ experiences of implementing physical education

The Curriculum and Assessment Policy Statement for Life Skills, Grades R-3 (CAPS) guides reception year (Grade R) teachers in planning and implementing physical education lessons, as part of the Life Skills Programme for Foundation Phase (Department of Basic Education (DBE), 2011). However, limited research has been conducted regarding the experiences of Grade R teachers in South Africa when they implement physical education as part of the daily programme for Grade R. The aim of this study was to investigate the experiences and knowledge of Grade R teachers on the implementation of the physical education curriculum. A qualitative, interactive interpretative research was conducted in which seven Grade R teachers from a diversity of schools in the Cape Winelands Education District, South Africa, participated in an unstructured open-ended focus group interview. This resulted in the categorisation of themes into an interview framework by utilising the Interactive Qualitative Analysis (IQA) method of Northcutt and McCoy (2004). The interview framework guided the semi-structured individual interview questions and classroom observations of four Grade R teachers during physical education lessons. Results indicated that the Grade R teachers shared similar needs and challenges in the teaching of physical education. The challenges included on-going quality pre- and in-service training, support from Life Skills Foundation Phase Subject Advisors, interpretation of the CAPS document, assistance in planning for physical education in the daily Grade R programme, as well as lack of time and inadequacy of available space. Policy recommendations to address the challenges are proffer

T cell responses to SARS-1 CoV-2 spike cross-recognize Omicron

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations1,2 that contribute to escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell responses, induced by vaccination or infection, cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19, and is linked to early clinical observations from South Africa and elsewhere9–12