Abstract
Background
This mixed methods study explored how social media use informed physical activity and diet-related behaviours, and self-perceived Quality of Life (QoL) during COVID-19, and ...assessed the contextual factors that drive social media use for health-related behaviour change in diverse groups. During the COVID-19 lockdown periods there were reported changes to social media use and health behaviours, and this gave an opportunity to investigate potential relationships.
Methods
An explanatory sequential research design of two parts was used: (1) An online survey that assessed social media use in relation to physical activity levels, diet quality and QoL (
n
= 786;
M
age 45.1 ± 19.1 (range 16–88) years; Female =69%); (2) 20 purposive focus groups (
n
= 69;
M
age = 52.88 ± 18.45 years, Female
n
= 68%) to understand the contextual factors that drive social media use for health-related behaviour change. Descriptive and thematic analysis were conducted.
Results
Participants in this study reported that social media facilitated the self-management of behaviours related to physical activity, diet and QoL, through access to information to inform workouts and dietary quality, and the opportunities for interaction with peers, family members and within social groups. Contextual factors including work, home and lifestyle arrangements, pre-existing health-related knowledge and behaviours, and the perceived value of social media for health influenced the relationship between social media use and self-reported outcomes. Social media influencers, peers/family members, and official organisations influenced the application of health-related information accessed via social media.
Conclusions
The evidence shows that participants were critical users of social media and were able to use social media to derive benefit for their health and wellbeing. Detailed guidance for those who use social media, as well as those who recommend and endorse social media content is required to maximise the potential of social media to support health behaviours. Future public health strategies and social media interventions should acknowledge diversity in contextual factors driving social media use for health behaviour change.
SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which ...lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.
•mRNA-1273 vaccine induces spike antibodies that are able to leverage FcR binding across VOCs•Convalescent spike antibodies interact with VOCs but exhibit compromised FcR binding•VOCs differentially affect Fc effector functions in natural infection and vaccination•mRNA-1273-induced antibodies might confer protection independent of neutralization
SARS-CoV-2 mRNA vaccines provide cross-variant protection against COVID-19. Whether this is mediated strictly via neutralization or is linked to effector functions that may limit, rather than block, transmission remains unknown. Kaplonek et al. show that mRNA-1273-vaccination-induced antibodies preserve Fc effector responses across variants of concern, whereas antibodies induced following natural infection show compromised interactions with Fc-receptors.
Neutrophils, the most abundant white blood cell, play a critical role in anti-pathogen immunity via phagocytic clearance, secretion of enzymes and immunomodulators, and the release of extracellular ...traps. Neutrophils non-specifically sense infection through an array of innate immune receptors and inflammatory sensors, but are also able to respond in a pathogen/antigen-specific manner when leveraged by antibodies via Fc-receptors. Among neutrophil functions, antibody-dependent neutrophil phagocytosis (ADNP) results in antibody-mediated opsonization, enabling neutrophils to sense and respond to infection in a pathogen-appropriate manner. Here, we describe a high-throughput flow cytometric approach to effectively visualize and quantify ADNP and its downstream consequences. The assay is easily adaptable, supporting both the use of purified neutrophils or white blood cells, the use of purified Ig or serum, and the broad utility of any target antigen. Thus, this ADNP assay represents a high-throughput platform for the in-depth characterization of neutrophil function.
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•A high-throughput antibody-dependent neutrophil phagocytosis (ADNP) assay was developed.•This flow cytometry assay is flexible and can be easily adapted to any pathogen.•Analysis of sample sets by ADNP assay is fast, robust and cost-effective.•Additional neutrophil functions can be profiled in secondary analyses.
The human brain is a complex, three‐dimensional structure. To better recapitulate brain complexity, recent efforts have focused on the development of human‐specific midbrain organoids. Human ...iPSC‐derived midbrain organoids consist of differentiated and functional neurons, which contain active synapses, as well as astrocytes and oligodendrocytes. However, the absence of microglia, with their ability to remodel neuronal networks and phagocytose apoptotic cells and debris, represents a major disadvantage for the current midbrain organoid systems. Additionally, neuroinflammation‐related disease modeling is not possible in the absence of microglia. So far, no studies about the effects of human iPSC‐derived microglia on midbrain organoid neural cells have been published. Here we describe an approach to derive microglia from human iPSCs and integrate them into iPSC‐derived midbrain organoids. Using single nuclear RNA Sequencing, we provide a detailed characterization of microglia in midbrain organoids as well as the influence of their presence on the other cells of the organoids. Furthermore, we describe the effects that microglia have on cell death and oxidative stress‐related gene expression. Finally, we show that microglia in midbrain organoids affect synaptic remodeling and increase neuronal excitability. Altogether, we show a more suitable system to further investigate brain development, as well as neurodegenerative diseases and neuroinflammation.
Main Points
Microglia were efficiently integrated into midbrain organoids.
Oxidative stress‐related genes are downregulated in organoids with microglia.
Gene expression and electrophysiology suggest a better neuronal functionality upon coculture.
While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses ...over the course of EBV infection and to gain a better understanding of the potential contribution of antibody (Ab) function to viral control, we comprehensively profiled Ab specificities and Fc-functionalities using systems serology and VirScan. Ab functions against latent (EBNA1), early (p47/54) and two late (gp350/220 and VCA-p18) EBV proteins were overall modest and/or short-lived, differing from humoral responses induced during acute infection by other viruses such as HIV. In the first year post infection, only p18 elicited robust IgM-driven complement deposition and IgG-driven neutrophil phagocytosis while responses against EBNA-1 were largely Fc-functionally silent and only matured during chronic infection to drive phagocytosis. In contrast, Abs against Influenza virus readily mediated broad Fc-activity in all participants. These data suggest that EBV evades the induction of robust Fc-functional Abs, potentially due to the virus’ life cycle, switching from lytic to latent stages during infection.
Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific ...development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.
The establishment of a long-lived viral reservoir is the key obstacle for achieving an HIV-1 cure. However, the anatomic, virologic, and immunologic features of the viral reservoir in tissues during ...antiretroviral therapy (ART) remain poorly understood. Here we present a comprehensive necroscopic analysis of the SIV/SHIV viral reservoir in multiple lymphoid and non-lymphoid tissues from SIV/SHIV-infected rhesus macaques suppressed with ART for one year. Viral DNA is observed broadly in multiple tissues and is comparable in animals that had initiated ART at week 1 or week 52 of infection. In contrast, viral RNA is restricted primarily to lymph nodes. Ongoing viral RNA transcription is not the result of unsuppressed viral replication, as single-genome amplification and subsequent phylogenetic analysis do not show evidence of viral evolution. Gag-specific CD8+ T cell responses are predominantly observed in secondary lymphoid organs in animals chronically infected prior to ART and these responses are dominated by CD69+ populations. Overall, we observe that the viral reservoir in rhesus macaques is widely distributed across multiple tissue sites and that lymphoid tissues act as a site of persistent viral RNA transcription under conditions of long-term ART suppression.
A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia ...Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8+ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8+ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
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•Generated MVA-based COVID-19 vaccine encoding prefusion-stabilized spike (MVA/S)•MVA/S vaccination induces strong nAb response and CD8+ T cell response in macaques•MVA/S vaccine protects macaques from SARS-CoV-2 infection and lung immunopathology•MVA/S vaccine prevents infection-induced inflammation and B cell abnormalities in lungs
Modified vaccinia Ankara (MVA) vector-based vaccines are attractive because of their excellent safety and ability to induce long-lived humoral and cellular immunity in humans. Routhu et al. show that an MVA-based COVID-19 vaccine encoding prefusion-stabilized spike (MVA/S) induces strong neutralizing antibody and CD8+ T cell responses and protects macaques from SARS-CoV2 infection, immunopathology, and infection-induced B cell abnormalities in the lungs.
Abstract
There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent ...adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.
Background
Assessment of the Core Entrustable Professional Activities for Entering Residency requires direct observation through workplace‐based assessments (WBAs). Single‐institution studies have ...demonstrated mixed findings regarding the reliability of WBAs developed to measure student progression towards entrustment. Factors such as faculty development, rater engagement and scale selection have been suggested to improve reliability. The purpose of this investigation was to conduct a multi‐institutional generalisability study to determine the influence of specific factors on reliability of WBAs.
Methods
The authors analysed WBA data obtained for clerkship‐level students across seven institutions from 2018 to 2020. Institutions implemented a variety of strategies including selection of designated assessors, altered scales and different EPAs. Data were aggregated by these factors. Generalisability theory was then used to examine the internal structure validity evidence of the data. An unbalanced cross‐classified random‐effects model was used to decompose variance components. A phi coefficient of >0.7 was used as threshold for acceptable reliability.
Results
Data from 53 565 WBAs were analysed, and a total of 77 generalisability studies were performed. Most data came from EPAs 1 (n = 17 118, 32%) 2 (n = 10 237, 19.1%), and 6 (n = 6000, 18.5%). Low variance attributed to the learner (<10%) was found for most (59/77, 76%) analyses, resulting in a relatively large number of observations required for reasonable reliability (range = 3 to >560, median = 60). Factors such as DA, scale or EPA were not consistently associated with improved reliability.
Conclusion
The results from this study describe relatively low reliability in the WBAs obtained across seven sites. Generalisability for these instruments may be less dependent on factors such as faculty development, rater engagement or scale selection. When used for formative feedback, data from these instruments may be useful. However, such instruments do not consistently provide reasonable reliability to justify their use in high‐stakes summative entrustment decisions.
Through examination of 53,000 workplace‐based assessments at 7 schools, no factors were found to be consistently associated with reliability, leading to the conclusion that these assessments are best used for formative feedback only.
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